•
Eeefm Doutor Francisco De Albuquerque Montenegro
Prévia do material em texto
<p>ADVANCE PRAISE FOR THE MENOPAUSE BRAIN</p><p>“In a society that often downplays the significance of menopause and its</p><p>impact on women’s lives, Dr.Mosconi’s book serves as a rallying cry for</p><p>embracing this transformative period with knowledge and empowerment.</p><p>Her insights remind me of the importance of fostering a sense of</p><p>community and support among women, a sentiment I hold dear in my own</p><p>work.”</p><p>—Mary Claire Haver, MD, bestselling author of The Galveston Diet</p><p>“Every woman should know that menopause is more than just mood and</p><p>hot flashes; it can profoundly impact brain health and function. Dr. Lisa</p><p>Mosconi stands as a foremost expert on the menopause brain. This</p><p>outstanding new book is a must-read, and I wholeheartedly recommend it.”</p><p>—Naomi Watts</p><p>“Written and referenced with care but phrased in a lighthearted, easy-to-</p><p>understand style, this book is highly recommended for women who want to</p><p>actively participate in preserving their brain’s health as they approach and</p><p>progress through perimenopause and menopause.”</p><p>—Avrum Bluming, MD, co-author of Estrogen Matters</p><p>“In The Menopause Brain, Dr.Lisa Mosconi expertly guides us so that we</p><p>do not feel alone in this journey, providing us with hope and achievable,</p><p>empowering solutions drawn from her pioneering research, holistic training,</p><p>and personal experience.”</p><p>—Tamsen Fadal, author of The New Single</p><p>“When it comes to menopause, it feels as if we have no information,</p><p>misinformation, or what’s out there is too chaotic and conflicting to make</p><p>sense. Enter Lisa Mosconi. Hallelujah and thank you! Written with a</p><p>neuroscientist’s mind and a woman’s heart, this book is packed with</p><p>evidence-based, empowering information on all things menopause. For</p><p>every woman living any phase of menopause, this is your required reading.”</p><p>—Lisa Genova, bestselling author of Still Alice</p><p>“The Menopause Brain delivers the comprehensive, science-backed</p><p>information we need about menopause. It both inspires and empowers</p><p>women to thrive during this stage of life.”</p><p>—Jolene Brighten, NMD, FABNE, bestselling author of Beyond the Pill</p><p>“Dr.Mosconi is finally answering the questions that have been ignored for</p><p>far too long. The Menopause Brain is deeply researched yet accessible and</p><p>provides the gold standard for understanding the role of estrogen in the</p><p>female brain.”</p><p>—Sharon Malone, MD, author of Grown Woman Talk</p><p>“The Menopause Brain gives you the tools you need to make sure that your</p><p>beautiful mind is vibrant and that your brain stays healthy. And all of this</p><p>from none other than Dr. Lisa Mosconi, who has the greatest mind—and</p><p>biggest heart—in the neuroscience of menopause.”</p><p>—Aviva Romm, MD, New York Times bestselling author of Hormone Intelligence</p><p>“Long misunderstood, menopause gets a fresh narrative in The Menopause</p><p>Brain. Filled with groundbreaking research and actionable advice from a</p><p>leading neuroscientist, this book is essential reading for anyone navigating</p><p>this transformative period.”</p><p>—Ellen Vora, MD, author of The Anatomy of Anxiety</p><p>an imprint of Penguin Random House LLC</p><p>penguinrandomhouse.com</p><p>Copyright © 2024 by Lisa Mosconi</p><p>Penguin Random House supports copyright. Copyright fuels creativity, encourages diverse voices,</p><p>promotes free speech, and creates a vibrant culture. Thank you for buying an authorized edition of</p><p>this book and for complying with copyright laws by not reproducing, scanning, or distributing any</p><p>part of it in any form without permission. You are supporting writers and allowing Penguin Random</p><p>House to continue to publish books for every reader.</p><p>Library of Congress Cataloging-in-Publication Data</p><p>Names: Mosconi, Lisa, author.</p><p>Title: The menopause brain: new science empowers women to navigate the pivotal transition with</p><p>knowledge and confidence / Lisa Mosconi, PhD.</p><p>Description: New York: Avery, an imprint of Penguin Random House, [2024] | Includes</p><p>bibliographical references and index.</p><p>Identifiers: LCCN 2023025435 (print) | LCCN 2023025436 (ebook) | ISBN 9780593541241</p><p>(hardcover) | ISBN 9780593541258 (epub)</p><p>Subjects: LCSH: Menopause—Popular works. | Menopause—Psychological aspects—Popular</p><p>works. | Menopause—Hormone therapy—Popular works. | Menopause—Alternative—Popular</p><p>works.</p><p>Classification: LCC RG186 .M67 2024 (print) | LCC RG186 (ebook) | DDC 618.1/75—</p><p>dc23/eng/20231117</p><p>LC record available at https://lccn.loc.gov/2023025435</p><p>LC ebook record available at https://lccn.loc.gov/2023025436</p><p>Cover design: Caroline Johnson</p><p>Cover images: Getty Images</p><p>Book design by Neuwirth & Associates, adapted for ebook by Kelly Brennan</p><p>Neither the publisher nor the author is engaged in rendering professional advice or services to the</p><p>individual reader. The ideas, procedures, and suggestions contained in this book are not intended as a</p><p>substitute for consulting with your physician. All matters regarding your health require medical</p><p>supervision. Neither the author nor the publisher shall be liable or responsible for any loss or damage</p><p>allegedly arising from any information or suggestion in this book.</p><p>While the author has made every effort to provide accurate telephone numbers, Internet addresses,</p><p>and other contact information at the time of publication, neither the publisher nor the author assumes</p><p>any responsibility for errors, or for changes that occur after publication. Further, the publisher does</p><p>not have any control over and does not assume any responsibility for author or third-party websites or</p><p>their content.</p><p>http://www.penguinrandomhouse.com/</p><p>https://lccn.loc.gov/2023025435</p><p>https://lccn.loc.gov/2023025436</p><p>All names and identifying characteristics have been changed to protect the privacy of the individuals</p><p>involved.</p><p>pid_prh_6.3_146464156_c0_r0</p><p>To all women—our ancestors, our descendants, and all of you blazing</p><p>the trail with me as we speak.</p><p>CONTENTS</p><p>Foreword by Maria Shriver</p><p>PART 1</p><p>THE BIG M</p><p>CHAPTER 1. You Are Not Crazy</p><p>CHAPTER 2. Busting the Bias Against Women and Menopause</p><p>CHAPTER 3. The Change Nobody Prepared You For</p><p>CHAPTER 4. Menopause Brain Is Not Just Your Imagination</p><p>PART 2</p><p>THE BRAIN-HORMONE CONNECTION</p><p>CHAPTER 5. Brain and Ovaries: Partners in Time</p><p>CHAPTER 6. Putting Menopause in Context: The Three P’s</p><p>CHAPTER 7. The Upside of Menopause</p><p>CHAPTER 8. The Why of Menopause</p><p>Part 3</p><p>HORMONAL AND NONHORMONAL THERAPIES</p><p>CHAPTER 9. Estrogen Therapy for Menopause</p><p>CHAPTER 10. Other Hormonal and Nonhormonal Therapies</p><p>CHAPTER 11. Cancer Therapies and “Chemo Brain”</p><p>CHAPTER 12. Gender-Affirming Therapy</p><p>PART 4</p><p>LIFESTYLE AND INTEGRATIVE HEALTH</p><p>CHAPTER 13. Exercise</p><p>CHAPTER 14. Diet and Nutrition</p><p>CHAPTER 15. Supplements and Botanicals</p><p>CHAPTER 16. Stress Reduction and Sleep Hygiene</p><p>CHAPTER 17. Toxins and Estrogen Disrupters</p><p>CHAPTER 18. The Power of a Positive Mindset</p><p>Acknowledgments</p><p>Notes</p><p>Index</p><p>FOREWORD</p><p>I AM SO HAPPY that you picked up The Menopause Brain. Good for you. You</p><p>just did yourself and your brain a huge favor! Now that you have this book,</p><p>you will not have to navigate perimenopause, menopause, or even your</p><p>postmenopausal life alone. You now have at your fingertips the most up-to-</p><p>date information about what is happening to your brain and your body—and</p><p>why. What a gift!</p><p>This book is crucial because every woman, if she lives long enough, will</p><p>go through menopause at some point in her life. And every woman will</p><p>wonder why, in addition to losing her period and fertility, she may be</p><p>experiencing sudden heart palpitations, anxiety, depression, lack of</p><p>concentration, hot flashes, night sweats, mood swings, and sleep</p><p>disturbances. The list of symptoms is long and varied. Menopause is a</p><p>function of the brain that plays havoc with a woman’s body and her outlook</p><p>on life. Indeed, all of these erratic emotions and symptoms can make a</p><p>woman feel crazy if she is not reassured that they are normal. This book</p><p>will do exactly that.</p><p>I wish this book had been around when I was going through</p><p>perimenopause and menopause because for millions of women like me,</p><p>when The Big M, as I call it, came knocking, we were given little</p><p>information</p><p>hormones</p><p>may be lower today and higher tomorrow. Their range is quite wide,</p><p>too. Additionally, a high FSH level in a woman who is having hot</p><p>flashes and is missing her period does not eliminate the likelihood</p><p>that she is still in perimenopause. Blood tests are particularly tricky</p><p>for women in perimenopause, since the hormone levels change</p><p>throughout the cycle, and the cycle is now irregular, which only</p><p>increases the variability. In addition, contrary to popular belief,</p><p>estrogen levels fluctuate widely in perimenopause, sometimes</p><p>ending up being higher than expected rather than lower. Also keep</p><p>in mind that hormonal contraception such as the pill and some IUDs</p><p>can stop menstruation and affect the accuracy of the FSH test,</p><p>making it difficult to determine whether one is past menopause or</p><p>not.</p><p>Table 2. Laboratory Tests for Menopause: Reference Ranges</p><p>PREMENOPAUSE POSTMENOPAUSE</p><p>Follicular phase Ovulation Luteal phase</p><p>Estradiol (pg/ml) 12.4–233 41–398 22.3–341</p><p>why they are recommending it. Keep in mind</p><p>that there are situations where oophorectomy is indicated even in</p><p>absence of cancer or cancer risk, and other situations where ovarian</p><p>conservation is more appropriate.</p><p>To be absolutely clear, nobody is telling patients to decline</p><p>necessary treatment. The point is that oftentimes the possible risks</p><p>resulting from these surgeries are not made sufficiently clear to</p><p>patients. “I wish I had known” is something I’ve heard way too</p><p>many times. It’s important to understand what these procedures</p><p>involve, both in the short and long term, and what treatment options</p><p>are available, so that each and every woman can make an informed</p><p>choice for herself and her own health.</p><p>Table 3. Bilateral Salpingo-Oophorectomy (BSO): Current Guidelines</p><p>Indications for BSO</p><p>Suspected or confirmed gynecological malignancy</p><p>Risk reduction surgery (BRCA1 and BRCA2 gene mutations, Lynch syndrome,</p><p>Peutz-Jeghers syndrome, and a strong family history of ovarian cancer) only</p><p>after completion of childbearing and over the age of thirty-five</p><p>Other indications for BSO</p><p>Chronic pelvic pain</p><p>Pelvic inflammatory disease</p><p>Severe endometriosis</p><p>Considerations for ovarian preservation</p><p>Premenopausal women without genetic predisposition to cancer</p><p>Women with no significant family history of ovarian cancer</p><p>Women with no adnexal pelvic pathology (a lump in tissue near the uterus,</p><p>usually in the ovary or fallopian tube)</p><p>Postmenopausal women with no additional risk factors</p><p>Does menopause affect a woman only physically?</p><p>Most certainly not. Menopause is a mind-body experience. When</p><p>hormones change, we change too. Menopause isn’t just a</p><p>reproductive phenomenon; it impacts a woman’s thoughts, feelings,</p><p>self-image, and behavior. In the next chapter, we’ll clarify how</p><p>many of the symptoms of menopause are in fact a reaction to the</p><p>brain’s own menopausal journey.</p><p>4</p><p>Menopause Brain Is Not Just Your</p><p>Imagination</p><p>NO TWO MENOPAUSES ARE ALIKE</p><p>During menopause, the phase “hot and bothered” takes on a whole new</p><p>meaning. While generally regarded as a singular event, menopause is more</p><p>like a syndrome coming with an array of well over thirty different</p><p>symptoms that appear and disappear according to the woman in question.</p><p>To make matters even more confusing, one may experience some or none of</p><p>these symptoms. Generally, a lucky 10 to 15 percent of women report no</p><p>changes at all aside from irregular menstrual periods that stop when</p><p>menopause is reached. The vast majority, though, experience several</p><p>hundred unique symptom combinations.</p><p>Further, some symptoms are somatic, or of the body, impacting you from</p><p>the neck down, while others are neurological, or from the brain. Notably,</p><p>the menopause repertoire features at least as many brain symptoms as</p><p>bodily ones, though it’s easy to confuse one with the other. For example,</p><p>many women think that hot flashes are a sign that there’s something wrong</p><p>with their skin. But the skin has nothing to with that. Hot flashes are</p><p>triggered by the brain and are a legit neurological symptom. Let’s delve</p><p>deeper into the distinction between these symptom types.</p><p>The most common bodily symptoms of menopause are wide ranging and</p><p>impactful. They include changes in menstruation and period frequency, as</p><p>well as genitourinary symptoms like vaginal dryness, painful intercourse,</p><p>stress incontinence, or overactive bladder. Muscular changes manifest as</p><p>joint pain and stiffness, muscle tension, and aches, while bone-related</p><p>symptoms include bone frailty and an increased risk of osteoporosis.</p><p>Breast-related changes can also occur, such as breast soreness, loss of breast</p><p>fullness, and swelling. However, it’s crucial not to overlook the less-</p><p>discussed bodily symptoms of menopause that can significantly impact</p><p>women’s lives and well-being. These include irregular heartbeat and</p><p>palpitations, which can be very scary, as well as changes in body</p><p>composition, weight gain, and slower metabolism, along with digestive</p><p>issues, bloating, acid reflux, and nausea. Additional changes encompass</p><p>thinning hair, brittle nails, dry skin, and itchiness; changes in body odor;</p><p>changes in taste or dry or burning mouth; tinnitus, muffled hearing, or</p><p>sensitivity to noise; and even the development of new allergies. These</p><p>symptoms should not be taken lightly, as they can be overwhelming to deal</p><p>with on their own. Some may even lead to the misconception that your</p><p>body is betraying you or make you feel as if you’re going crazy or losing</p><p>control.</p><p>However, it is the brain-related effects of menopause that typically</p><p>become the major cause of concern for most women. While some may</p><p>sound familiar, like the telltale hot flashes mentioned above, others may be</p><p>surprising (or perhaps you’ll be surprised to learn that they also come from</p><p>the brain). The hormonal chaos of midlife can set off changes not only in</p><p>body temperature but also in mood, sleep patterns, stress levels, libido, and</p><p>cognitive performance. Importantly, these shifts can occur without any hot</p><p>flashes. Furthermore, some women develop neurological occurrences like</p><p>dizzy spells, fatigue, headaches, and migraines. Meanwhile, others report</p><p>more extreme symptoms, including severe depression, intense anxiety,</p><p>panic attacks, and even what’s referred to as electric shock sensations. All</p><p>these symptoms originate not in the ovaries, but in the brain. Yet despite</p><p>significant progress in understanding the bodily aspects of menopause, we</p><p>are only just beginning to grasp the full impact of the emotional, behavioral,</p><p>and cognitive shifts that can arise during this transition. Unfortunately, few</p><p>women, and perhaps fewer doctors, are fully aware of how common these</p><p>symptoms are. What many also don’t realize is how disruptive, intense, and</p><p>severe they can be. That’s why we are here. In this chapter, we’ll go over</p><p>the core “brain symptoms” of menopause.</p><p>It’s Getting Hot in Here</p><p>While the gradual disappearance of your period might not immediately</p><p>catch your attention, hot flashes, for one, are hard to ignore. Hot flashes are</p><p>considered the cardinal feature of menopause, experienced by as many as</p><p>85 percent of all women. The medical term for hot flashes is vasomotor</p><p>symptoms, clarifying that they are caused by the constriction or dilation of</p><p>blood vessels. This results in a sudden rush of heat, usually felt across the</p><p>face, neck, and chest. Your skin might redden as if you’re blushing or</p><p>mounting a fever, and it’s common to break into a sweat just as intensely. If</p><p>you lose too much body heat at once, you might get chills instead.</p><p>Calling this experience a flash, however, is misleading. Here one minute</p><p>and gone the next? No way. These signs of menopause can last at least a</p><p>few minutes but can continue for up to an hour, which strains anyone’s</p><p>definition of a flash. Not only do they take their time dissipating once</p><p>you’re having one, but they can stick around in your life for quite some</p><p>time. The average woman experiences hot flashes for three to five years,</p><p>but many can have them for ten years or longer. Scientists have identified</p><p>four patterns when it comes to hot flashes:</p><p>The lucky few: About 15 percent of women never have a hot flash.</p><p>Late-onset hot-flashers: Women who experience their first hot flash</p><p>only close to or after their final menstrual period. About a third of</p><p>all women fall in this group.</p><p>Early onset hot-flashers: Women who begin to experience these</p><p>symptoms several years before their final menstrual period.</p><p>Fortunately, hot flashes tend to end as the menstrual period does.</p><p>Super-flashers: Women who experience hot flashes early in life,</p><p>with symptoms lasting well past menopause. About one in four</p><p>women fall into this category. Smokers (past and current) and those</p><p>who are more than moderately overweight are more likely to be</p><p>super-flashers.</p><p>Ethnicity, lifestyle, and cultural factors likely play a role, too. African</p><p>American and Afro-diasporic women tend to experience more frequent and</p><p>severe hot flashes than their Caucasian counterparts, whereas Asian women</p><p>report</p><p>fewer, for reasons that are under investigation.</p><p>Running the gamut from uncomfortable to unbearable, hot flashes land a</p><p>one-two punch when they occur at night. In this case, they’re colloquially</p><p>referred to as night sweats. Until they experience them, most people don’t</p><p>appreciate the difference. According to medical textbooks, night sweats are</p><p>repeated episodes of heavy sweating during sleep, heavy enough to soak</p><p>your nightclothes or bedding. However, the real-life experience of night</p><p>sweats is a whole different ball game. According to women experiencing</p><p>them, night sweats are more aptly described as a five-alarm fire—a throw-</p><p>off-the-covers, dive-into-an-Arctic-cold-shower kind of experience. These</p><p>events can be profoundly debilitating, especially as they tend to occur</p><p>frequently, sometimes more than two or three times a night. This also goes a</p><p>long way to explaining why menopausal women have a reputation for</p><p>emotional volatility. When you can’t get a decent night’s rest for months, let</p><p>alone years at a time, and you’re dealing not only with the flashes but also</p><p>with clinical-level sleep deprivation . . . being in a bad mood seems</p><p>unavoidable.</p><p>In spite of women’s concerning experiences, most doctors persist in</p><p>thinking that vasomotor symptoms are nothing but a quality-of-life issue.</p><p>This is not the case. For instance, there is robust evidence that women who</p><p>experience hot flashes earlier in life might be at higher risk for heart</p><p>disease. Additionally, night sweats have been linked to presence of white-</p><p>matter lesions in the brain. These lesions result from a wearing away of the</p><p>brain’s white matter, the connective nerve fibers between neurons. There is</p><p>some evidence that the more night sweats one experiences, the more white-</p><p>matter lesions there are in the brain, potentially causing more severe issues</p><p>down the line. In a nutshell, hot flashes are very real symptoms that need</p><p>attending to before they become an actual problem. At a minimum, reports</p><p>of severe and frequent vasomotor symptoms should cue doctors to look</p><p>more closely at a woman’s cardiac health, as well as her brain health.</p><p>Fortunately, there are ways to alleviate, reverse, and even prevent</p><p>vasomotor symptoms, which we’ll review in later chapters.</p><p>An Emotional Roller Coaster</p><p>Roughly 20 percent of all women experience mood swings and depressive</p><p>symptoms during perimenopause and in the years immediately after the</p><p>final menstrual period. While menopause in and of itself does not cause</p><p>depression, it is pretty efficient at bringing on the blues. Changing</p><p>hormones can trigger mood swings that make you less able to cope with</p><p>things you’d normally let roll off your back. Moreover, for some women,</p><p>these hormonal dips can set off actual depressive episodes, especially for</p><p>those who’ve gone through major depression in the past. In such cases, it is</p><p>possible for symptoms to return during the menopause transition.</p><p>Additionally, even women who have never encountered depression in their</p><p>lives may find themselves grappling with it for the first time during</p><p>perimenopause.</p><p>Some of the most common emotional changes associated with</p><p>menopause include irritability, anxiety, and a diminished ability to deal with</p><p>life’s everyday hassles. Feelings of sadness, fatigue, lack of motivation, and</p><p>difficulty concentrating can also arise, along with emotional flatness,</p><p>trouble getting motivated, or a sense of overwhelm. It’s not uncommon for</p><p>crying or other releases to happen more often, more intensely, or seemingly</p><p>unexpectedly. While less prevalent, some women may even develop panic</p><p>attacks, while others report feeling downright rage—all easy fodder for the</p><p>stereotype of the mad, bad, and dangerous menopausal woman.</p><p>Considering what a life with ongoing hot flashes can be like, this moodiness</p><p>might not be such a mystery. However, menopausal depression often occurs</p><p>independent of hot flashes or other symptoms.</p><p>If you are experiencing mood swings or depressive symptoms, speak</p><p>with a healthcare provider who can help diagnose whether you are feeling</p><p>moody, depressed, or stressed out as a result of menopause—or whether</p><p>you are suffering from clinical depression of other origin. Since menopausal</p><p>depression and major depression share overlapping symptoms, it’s good to</p><p>get to the bottom of things and receive appropriate care. The good news:</p><p>Mood fluctuations are treatable. If emotional ups and downs during</p><p>perimenopause impact your normal daily activities or your relationships,</p><p>talk to your doctor about options. Thankfully, a variety of treatments are</p><p>available, including menopause hormone therapy and/or antidepressants, as</p><p>well as lifestyle adjustments, such as a specifically tailored diet and</p><p>exercise plan, which we’ll discuss in parts 3 and 4 of this book. Also keep</p><p>in mind that once hormones settle down after menopause, mood</p><p>fluctuations tend to stabilize, too.</p><p>Menopause Can Keep You Awake at Night</p><p>Poor sleep quality and sleep disturbances are lesser-known changes during</p><p>this phase of life, yet they’re highly prevalent. While sleep quality naturally</p><p>declines with age, menopause can add fuel to the fire, turning what would</p><p>have been a gradual process into a swift kick toward sleep deprivation. By</p><p>waking you up in the middle of the night, night sweats in particular make</p><p>for poor sleep if you’re lucky and full-blown insomnia if you’re not. Then</p><p>of course, as discussed above, if a person is not sleeping well, mood and</p><p>mental equilibrium are bound to be affected. Chronic sleep disturbances can</p><p>trigger not only low mood, anxiety, and potential depression but brain fog</p><p>and exhaustion, too. Lower estrogen levels further confound your brain,</p><p>decreasing your capacity to deal with stress in the first place. Even more</p><p>concerning is that sleep is essential in forming memories, quenching</p><p>inflammation, and even reducing the risk of cognitive impairment in old</p><p>age—all of which makes resting our busy minds crucial for the long haul.</p><p>It is therefore very important to address sleep disturbances that occur</p><p>during the menopause transition. Perhaps not surprisingly, perimenopausal</p><p>and postmenopausal women report more sleep issues than any other</p><p>segment of the human population. They are also more likely than other</p><p>people to report spin-off problems such as anxiety, stress, brain fog, and</p><p>depressive symptoms. According to the Centers for Disease Control and</p><p>Prevention:</p><p>More than half of all perimenopausal women sleep less than seven</p><p>hours a night. For context, over 70 percent of premenopausal</p><p>women sleep more than that—a significant jump.</p><p>One in three perimenopausal women have trouble not only falling</p><p>asleep but also staying asleep, waking up multiple times per night.</p><p>For some good news, while several women struggle deeply with sleep</p><p>throughout perimenopause, many eventually find a new normal, with their</p><p>sleep improving fairly quickly a few years after they transition to the</p><p>postmenopausal stage. However, just as many continue to wrestle with</p><p>poor-quality sleep and oftentimes insomnia. To make matters worse,</p><p>postmenopausal women are two to three times more likely than</p><p>premenopausal women to develop new sleep problems, such as sleep apnea.</p><p>While this disorder is typically considered a men’s issue, once menopause</p><p>kicks off, women are also at increased risk, possibly because of changes in</p><p>muscle tone. Sleep apnea is a chronic breathing disorder during which one</p><p>repeatedly stops breathing mid-sleep. Typically, this is due to a partial or</p><p>complete obstruction (or collapse) of the upper airway, often affecting the</p><p>base of the tongue and the soft palate, or due to a depressed signal from the</p><p>brain to initiate a breath. These events can last ten seconds or longer,</p><p>sometimes occurring hundreds of times per night, causing severe sleep</p><p>disruptions.</p><p>Sleep apnea is more common than you probably think. The National</p><p>Sleep Foundation reported that it likely affects as much as 20 percent of the</p><p>population, although as many as 85 percent of individuals with sleep apnea</p><p>don’t know they</p><p>have it. That seems to be particularly the case for women,</p><p>for two reasons. First, many women attribute the symptoms and effects of</p><p>sleep disorders (like daytime fatigue) to stress, overwork, or menopause,</p><p>rather than to sleep apnea. Second, the symptoms of sleep apnea are often</p><p>more subtle in women than in men (read, women snore less). As a result,</p><p>women tend to not seek evaluation for sleep apnea, which in turn delays</p><p>diagnosis and treatment.</p><p>Given the importance of sleep for your health, both physical and mental,</p><p>I strongly recommend that you get a proper sleep evaluation if you are</p><p>concerned that your sleep symptoms may be due to menopause, sleep</p><p>apnea, or a combination of the two. Treatments for sleep apnea are</p><p>available, which often include lifestyle changes and the use of a breathing</p><p>assistance device at night, such as a continuous positive airway pressure</p><p>(CPAP) machine. Sleep disturbances due to menopause are also just as</p><p>important to address. As with the other symptoms so far, remedies are</p><p>available, which we’ll review in part 4.</p><p>Brain Fog Can Spark Fears of Dementia</p><p>Along with sweating and poor sleep often comes something many women</p><p>don’t anticipate: brain fog. Few things are more disconcerting than when</p><p>your brain feels like mush rather than the sharp and useful tool you’ve been</p><p>used to, or when your memory takes a turn for the worse. Although brain</p><p>fog is not a medical term, it aptly describes the fogginess in one’s thinking,</p><p>the mental fuzziness, and the difficulty processing information that often</p><p>accompany menopause. This phenomenon is perhaps best described as</p><p>feeling that you are enveloped in cotton wool, finding it hard to absorb and</p><p>recall information or concentrate on everyday tasks, which now require</p><p>greater concentration, time, and effort. The most common complaints</p><p>include things like forgetting what you walked into a room for, struggling to</p><p>remember words and familiar names, or losing focus during a mental task.</p><p>One of our patients described this experience in these words: “I just don’t</p><p>feel like myself anymore. I feel like a shell of my former self.” Another</p><p>patient told me she was feeling lethargic, almost spent: “No matter what I</p><p>do, my brain just won’t turn on.”</p><p>According to recent statistics, over 60 percent of all perimenopausal and</p><p>postmenopausal women struggle with brain fog. The experience is so</p><p>marked that it can disturb one’s sense of efficiency, especially when</p><p>memory lapses crop up. It’s important to realize that forgetfulness can spike</p><p>during perimenopause, which can feed fears not only of going crazy but of</p><p>experiencing early dementia. In other words, we are looking at millions of</p><p>women in the prime of life who suddenly feel like the rug has been pulled</p><p>out from under them—blindsided by their bodies, let down by their brains,</p><p>and failed by their doctors, who also may not realize that those are</p><p>symptoms of menopause.</p><p>Here are some examples of what brain fog may feel like:</p><p>Problems with short-term memory; forgetting details like names,</p><p>dates, and sometimes events; forgetting things that you usually have</p><p>no trouble remembering (memory lapses); confusing dates and</p><p>appointments.</p><p>Difficulty concentrating; having a reduced focus or a shorter</p><p>attention span (easily spacing out).</p><p>Feeling mentally slower than usual (mental fatigue); taking longer</p><p>to finish things or feeling disorganized, with slower thinking and</p><p>processing.</p><p>Trouble multitasking, like answering the phone while typing,</p><p>without losing track of one task; it’s harder to do more than one</p><p>thing at a time.</p><p>Fumbling for the right word or phrase; being unable to find the right</p><p>words to finish a sentence; losing your train of thought.</p><p>Having trouble following the flow of a conversation.</p><p>Feeling sluggish or tired or lacking energy.</p><p>That’s the bad news. The good news is that experiencing menopausal</p><p>brain fog or forgetfulness does not mean that one is necessarily developing</p><p>dementia. As a specialist in the field, I want to reassure everyone that</p><p>there’s a big difference between perceiving a decline in brainpower and</p><p>being clinically impaired. Although the symptoms listed above may</p><p>inconvenience and challenge you beyond your patience, the power surges</p><p>and sputters you’re experiencing do not mean that the lights are going out</p><p>(although the “find my phone” app on cell phones may become your new</p><p>BFF). In all seriousness, in medicine, brain fog is referred to as mental</p><p>fatigue, or more technically, as subjective cognitive decline. The key word</p><p>here is subjective. When applied to midlife women, this definition indicates</p><p>that patients are “aware of a decline from a previous level of cognitive</p><p>functioning, in the absence of objective impairment.” In other words,</p><p>although you may feel that you’re underperforming relative to your usual</p><p>standards (which involve a subjective perception), chances are, your</p><p>performance is objectively within the appropriate reference range—or</p><p>consistent with that of other people your age.</p><p>To give you a better sense of how this plays out, let’s say that I asked you</p><p>to take a test called a Mini-Mental State Exam (MMSE). This test is</p><p>commonly used to measure cognitive performance. The maximum score is</p><p>30. A score of 25 or higher reflects normal cognitive performance. A score</p><p>of 24 or below indicates possible cognitive impairment instead. The lower</p><p>the score, the more likely a person is to have dementia.</p><p>So let’s say that, before “menopausing,” you got a score of 30. As you</p><p>start going through the transition, that 30 may become a 29 or a 28. While</p><p>that’s a small change, one can totally feel it. Appointments may get missed,</p><p>keys may be misplaced, and names may not come to mind as easily as</p><p>before. Still, although your performance has indeed declined relative to</p><p>your own baseline, this change does not put you in the “impaired” range,</p><p>and therefore does not indicate a cognitive deficit. For context, consider the</p><p>brain imaging work we reviewed in chapter 1, showing brain changes</p><p>before and after menopause. As dramatic as those changes appear, they are</p><p>not indicative of a brain deficiency. They are a change from a previous level</p><p>of brain energy. What those scans show is not dementia, but menopause.</p><p>So what is really going on? While menopausal brain fog hasn’t been the</p><p>subject of much research, there is robust evidence that typically it is a</p><p>temporary change, and that mental acuity recuperates after menopause. This</p><p>phenomenon is well described in one of the most extensive studies thus far,</p><p>the Study of Women’s Health Across the Nation (SWAN). The SWAN</p><p>traced cognitive performance in over 2,300 midlife women over several</p><p>years. Many of these women were at the premenopausal stage when the</p><p>study began. This way, the investigators were able to compare cognitive</p><p>performance in the same women, before and after menopause, similar to</p><p>what we do with our brain scans. The results: Over time, as the</p><p>premenopausal women in the study entered perimenopause, their scores on</p><p>some cognitive tests did indeed show a decrease. Specifically, the</p><p>participants had a harder time remembering some information and needed</p><p>more time to complete some of those tests than before they were</p><p>perimenopausal. Crucially, the numbers bounced back a few years later,</p><p>after these same women reached the postmenopausal stage, after which</p><p>cognitive performance returned more or less to previous scores.</p><p>For context, consider the brain imaging work we reviewed in chapter 1,</p><p>showing brain changes before and after menopause. As dramatic as those</p><p>changes appear, they are not indicative of a brain “deficiency.” They are a</p><p>change from a previous level of brain energy. What those scans show is not</p><p>dementia but menopause. As we’ll see in the next chapter, our latest studies</p><p>reveal that in many cases, the perimenopausal declines in brain energy</p><p>eventually stabilize, too—and that women’s brains have the ability to adjust</p><p>to menopause and carry on.</p><p>To sum it all up:</p><p>Women’s concerns about their cognitive functions are legitimate</p><p>and valid.</p><p>If a woman approaching or past menopause feels she is</p><p>having memory problems, no one should brush it off or attribute it</p><p>to a jam-packed schedule—or, worse, to “just being a woman.”</p><p>Some cognitive slippage is indeed common during the</p><p>perimenopausal and early postmenopausal years. In most cases,</p><p>these issues are short-lived and go away over time. While your brain</p><p>may feel off or muddy for a while, when the transition passes,</p><p>typically the clouds clear and the fog lifts.</p><p>Not to put too fine a point on it, but even during this phase, women</p><p>outperform men on those very same cognitive tests measuring memory,</p><p>fluency, and some forms of attention. That’s true both before and after</p><p>menopause. During the menopause transition, cognitive scores may take a</p><p>dip, bringing women’s performance effectively within men’s range. In other</p><p>words, the average menopausal woman performs just as well as the average</p><p>man of the same age, who is not, of course, in menopause. (Take that,</p><p>Darwin!)</p><p>With all that said, here’s an important caveat. These findings represent an</p><p>average effect. That is to say, the average woman transitioning to</p><p>menopause may experience some cognitive decline, which may either</p><p>remain stable or be followed by a rebound. But this word average hides the</p><p>reality that this is not true for all women. In fact, some don’t show any</p><p>changes in cognitive performance, which is great. But others show more</p><p>severe changes, which may be a warning that something serious is afoot. In</p><p>keeping with the example above, if your MMSE score has gone down from</p><p>30 or so to 24 or lower, that is an unusual change that needs further</p><p>evaluation. Women are not impervious to cognitive impairment—as we</p><p>discussed, two-thirds of all Alzheimer’s patients are women. For some,</p><p>cognitive performance may indeed deteriorate after menopause and become</p><p>a diagnosis of dementia later on. Likewise, in our brain imaging studies,</p><p>some women show less of a change as they go through menopause, while</p><p>for others, the changes in brain energy as well as in other important</p><p>functionalities are more severe. This is indeed a red flag for a higher risk of</p><p>developing dementia later in life. So what all this means for each woman</p><p>who may worry about brain fog in midlife is that we need to take this</p><p>information very seriously and take great care of our brains during</p><p>menopause and beyond.</p><p>Alzheimer’s disease spurs cloudy thinking, and it, too, manifests with</p><p>difficulty remembering things, coming up with the right words, and having</p><p>trouble organizing thoughts. So how are we supposed to tell the difference?</p><p>Generally, the memory changes that occur during menopause aren’t</p><p>functionally disabling—that is to say, they don’t severely interfere with</p><p>your daily life. They also either remain stable or resolve over time. Unlike</p><p>the brain fog associated with menopause, Alzheimer’s is a progressive</p><p>disease that worsens over time and interferes with your ability to function</p><p>and take care of yourself. For context, dementia isn’t forgetting where you</p><p>left your keys. Dementia is forgetting what keys are for.</p><p>If your cognitive issues during menopause negatively impact your daily</p><p>life and don’t seem to improve over time or with treatment, whether it be</p><p>medications or lifestyle modifications, you might want to seek out a</p><p>neurologist or a neuropsychologist. For instance, if you are three to four</p><p>years postmenopausal and you are still having serious concerns, this would</p><p>be a good time to be tested, even if just for peace of mind. I would also</p><p>recommend joining an Alzheimer’s prevention program like ours. Our</p><p>patients receive thorough medical exams, cognitive testing, and brain scans</p><p>over time, specifically to evaluate whether there are any risks that need</p><p>attending to. We then intervene by implementing evidence-based</p><p>recommendations aimed at supporting cognitive health and reducing the</p><p>risk of dementia. Many of the therapeutic and lifestyle options we apply in</p><p>our practice also apply to caring for the menopause brain and are described</p><p>in this book. As a further resource, our scientific papers are available</p><p>online, and my book The XX Brain is entirely focused on dementia</p><p>prevention for women.</p><p>Not in the Mood</p><p>Last but not least, let’s talk about sex. In both men and women, desire may</p><p>decrease with age. However, women are two to three times more likely to</p><p>be impacted. What causes a lessening of libido can be complex, but it is a</p><p>common concern with menopause, with as many as 30 percent of women</p><p>experiencing a drop in desire during those years—an effect that generally</p><p>peaks during perimenopause and early postmenopause. However, while</p><p>menopause has long been portrayed as a bummer for sex, recent studies</p><p>reveal that midlife sexuality is not that tidy after all. While it is true that</p><p>some menopausal women may gladly give up sex for sleep or chocolate,</p><p>others report quite the opposite, experiencing renewed interest and desire.</p><p>This tends to happen during the late postmenopausal phase, typically after</p><p>age sixty to sixty-five.</p><p>While we’re still studying the various reasons behind this variability,</p><p>there are some consistent factors at play. For example, vaginal dryness or</p><p>atrophy, which is the thinning, drying, and inflammation of the vaginal</p><p>walls that may occur during menopause, can render sex painful. Other</p><p>symptoms of menopause, such as hot flashes, insomnia, and fatigue, may</p><p>also undermine sexual motivation and interest, and sometimes negatively</p><p>impact self-esteem. In some cases, low libido may be originating in the</p><p>brain itself, an often-overlooked sign of hormonal turmoil. Let’s face it:</p><p>feeling exhausted, stressed, sleep deprived, and sweaty may not help your</p><p>appetite for sex.</p><p>However, scientists have found that your mindset matters, too. Changes</p><p>in libido have been linked, at least in part, to a woman’s attitude toward sex</p><p>before menopause. If we return to the SWAN project, in another study,</p><p>investigators worked with 1,390 midlife women for as long as fifteen years,</p><p>asking them to rate how important sex was to them as they moved through</p><p>menopause. About 45 percent of women in the survey indicated that sex did</p><p>indeed become less important to them as they traversed menopause. But the</p><p>remaining 55 percent either considered sex as consistently highly important</p><p>or didn’t consider sex very important to start with and stuck with that</p><p>viewpoint throughout their menopause. Interestingly, women who reported</p><p>having more satisfying sex, both from an emotional and a physical</p><p>standpoint, were more likely to rate sex as “highly important” at any age.</p><p>Those more likely to rate sex as “not very important” after menopause also</p><p>tended to have depressive symptoms, highlighting the impact of emotional</p><p>health on sexuality, among other things. Additionally, women who</p><p>underwent surgical menopause showed a more significant decrease in</p><p>desire, which may be due to their experiencing more abrupt hormonal</p><p>shifts. There’s a lot to consider surrounding this issue; solutions and</p><p>suggestions will be addressed in upcoming chapters, but as a quick preview,</p><p>some hormonal and nonhormonal therapies seem to make a real difference,</p><p>and so does cognitive therapy. If you look at your sexual health as another</p><p>aspect of your menopause that needs attention, now and for the future, it</p><p>makes sense to address any sources of disruption. Having a healthy sexual</p><p>life, if you wish, can be another invigorating aspect of your life during and</p><p>after menopause.</p><p>The Menopause Brain Is Real</p><p>Based on all the evidence so far, we are here today to introduce and</p><p>formalize the concept of menopause brain. It is important to redefine and</p><p>understand it from the perspective of the women who are living through it,</p><p>rather than through the narrow lens of societal perceptions or outdated</p><p>clinical practices.</p><p>Menopause brain encompasses a range of changes in body temperature</p><p>regulation, cognition, mood, sleep, energy, and libido experienced during</p><p>the menopausal transition. It can vary in severity and duration among</p><p>individuals, and not</p><p>all women will experience these changes. The most</p><p>common symptoms that collectively contribute to menopause brain include:</p><p>Hot flashes: Sudden feelings of intense heat accompanied by</p><p>sweating, rapid heartbeat, and flushing of the face and upper body.</p><p>Sleep difficulties: Disrupted sleep patterns, insomnia, or fragmented</p><p>sleep.</p><p>Mood changes: Mood swings, irritability, anxiety, or feelings of</p><p>sadness or depression.</p><p>Memory lapses: Memory issues, such as forgetfulness or having</p><p>trouble recalling names, dates, or details.</p><p>Difficulty concentrating: Reduced focus and attention span,</p><p>increased distractibility.</p><p>Slower cognitive processing: Mental fogginess or sluggishness,</p><p>trouble thinking clearly, more difficulty processing information or</p><p>making decisions.</p><p>Word retrieval problems: Trouble finding the right words or</p><p>expressing thoughts verbally.</p><p>Decreased multitasking abilities: Difficulty juggling multiple tasks</p><p>or switching between tasks, leading to feelings of being</p><p>overwhelmed.</p><p>Low energy: Fatigue, lack of motivation, and decreased overall</p><p>energy levels.</p><p>Low libido: Decreased sexual desire or interest in sexual activity.</p><p>We’ve established that the menopause brain is anything but a breeze. The</p><p>symptoms that may crop up during this life stage are very real and need</p><p>addressing. However, we don’t just have problems; we have solutions! No</p><p>woman needs to suffer unnecessarily because of menopause. For one, we</p><p>can feel a welcome relief discovering that several symptoms that appear</p><p>during the transition can just as often spontaneously disappear after</p><p>menopause. Having the variety of our experiences and concerns validated</p><p>also holds power and comfort in and of itself. The postmenopausal stage of</p><p>a woman’s life is not the “over and out” that society has mistakenly</p><p>signaled. Instead, it can come with relief and renewed energy, not to</p><p>mention a broader outlook on life.</p><p>Armed with this reassurance, we will now clarify how and why</p><p>menopause impacts the brain and the significance of this impact for</p><p>women’s health. This information is key for understanding menopause and</p><p>for choosing the best way to manage this important transition. In fact, the</p><p>symptoms of menopause can not only be reduced but often entirely</p><p>eliminated by following the program outlined in the chapters to come. It is</p><p>easier to then find further comfort in the prescription treatments available to</p><p>us, along with appropriate natural remedies and lifestyle modifications.</p><p>Postmenopausal women will also greatly benefit from these guidelines,</p><p>which are proven to protect and invigorate the mind at any age.</p><p>PA RT 2</p><p>THE BRAIN-HORMONE</p><p>CONNECTION</p><p>5</p><p>Brain and Ovaries: Partners in Time</p><p>THE BRAIN-OVARIES CONNECTION</p><p>The human brain may well be the most complex biological structure on</p><p>Earth. With its estimated 100 billion neurons and 100 trillion connections,</p><p>it’s the crown jewel of our species and the source of all the qualities that</p><p>make us human. It is the seat of intelligence, the interpreter of the senses,</p><p>the supervisor of behavior, and the initiator of body movement.</p><p>To achieve all this, the brain is in close contact and integrated with every</p><p>other part of the body, and very much shaped by all these interactions in</p><p>return. For women, one of the most extraordinary and consequential</p><p>connections is between our brain and our ovaries, its depth becoming clear</p><p>when we take a peek at evolution. The survival of a species ultimately</p><p>depends on reproduction and the relaying of its genes to future generations.</p><p>Our body is optimized to support this capability, with the brain in the</p><p>driver’s seat. This is important because human reproduction is complex,</p><p>involving the many physiological, emotional, and behavioral interactions</p><p>necessary to select a reproductive partner and then maintain the</p><p>relationships that make it easier to raise offspring. As a result, the female</p><p>brain has evolved to be not only intricately wired for reproduction but also</p><p>deeply integrated with our ovaries to ensure all these mechanisms are in</p><p>place.</p><p>THE NEUROENDOCRINE SYSTEM AND ITS ROUTES</p><p>These crucial connections are powered by the neuroendocrine system, a</p><p>network that connects the brain to the ovaries and to the rest of our</p><p>hormonal system, the complexity of which reveals a level of teamwork</p><p>between these organs that few have sufficiently fathomed. That’s where we</p><p>come in. Thanks to the close monitoring of estrogen by these regions, the</p><p>brain can coordinate the myriad physical and mental functions necessary for</p><p>reproduction and beyond. Straight ahead, a little primer: Neuroendocrine</p><p>System Anatomy 101.</p><p>Route 1. The HPG (Hypothalamic-Pituitary-Gonadal Axis)</p><p>Envision this system as a subway map with several stations, the brain at one</p><p>end and the ovaries at the other, as we spotlight the most important routes</p><p>and stops. The ovaries (aka gonads) are so strongly wired to the brain,</p><p>specifically to two structures called the pituitary and hypothalamus, that</p><p>medical textbooks identify these connections as a single entity: the</p><p>hypothalamic-pituitary-gonadal axis, or HPG. The HPG is the pillar of the</p><p>neuroendocrine system, dedicating itself to regulating reproductive</p><p>behavior at all stages of life. As shown in figure 5, eight major glands are</p><p>part of the HPG. Picture each gland as a stop on Route 1.</p><p>1. Pituitary gland. The first station on the HPG is the pituitary gland.</p><p>The size of a pea, this small but mighty gland has a big job: it</p><p>makes hormones that regulate the activity of all the other glands,</p><p>the ovaries included. As a matter of fact, the most important</p><p>hormones produced by the pituitary are FSH and LH—those</p><p>same hormones that prompt ovulation during our reproductive</p><p>years. The pituitary is also involved in making oxytocin</p><p>(responsible for contractions during labor and lactation</p><p>afterward), vasopressin (in charge of blood and water volume),</p><p>and growth hormones (promoting the development of the entire</p><p>human body, brain included).</p><p>Figure 5. The Neuroendocrine System</p><p>2. Hypothalamus. This gland monitors the entire nervous system on</p><p>behalf of the pituitary gland and flags anything requiring its</p><p>special attention. This gland is a big deal, as it’s in charge of</p><p>stimulating the production of LH and FSH by the pituitary,</p><p>which results in the production of estrogen and progesterone in</p><p>the ovaries. You could say it’s also head of homeostasis,</p><p>controlling body temperature, sleep patterns, appetite, and blood</p><p>pressure, therefore maintaining the body’s overall balance.</p><p>3. Pineal gland. Located in the brain’s very center, this gland receives</p><p>and conveys information about our environment’s current light-</p><p>dark cycle and secretes the hormone melatonin accordingly. Like</p><p>Mr.Sandman, we count on it to signal sleep.</p><p>4. Thyroid gland. Down in the neck, this butterfly-shaped beauty</p><p>regulates metabolism and temperature. The thyroid produces two</p><p>hormones you’re likely familiar with from your blood-test</p><p>results: T3 (triiodothyronine) and T4 (thyroxine). Attached to the</p><p>thyroid are four glands no larger than a grain of rice, called the</p><p>parathyroids. These tiny glands attend to calcium regulation,</p><p>which is important for bone health.</p><p>5. Thymus. Located in the upper chest, the thymus is like a</p><p>bodyguard, producing white blood cells to fight infections and</p><p>give abnormal cells the boot.</p><p>6. Pancreas. This organ-gland complex acts as a liaison between the</p><p>hormonal and the digestive systems. The pancreas produces</p><p>enzymes to assist digestion while also making two essential</p><p>hormones to control the amount of sugar in the bloodstream, like</p><p>the famous insulin.</p><p>7. Adrenal glands. This dynamic duo sits on top of your kidneys,</p><p>producing hormones involved in regulating your metabolism,</p><p>immune system, blood pressure, and stress response. Their claim</p><p>to fame is adrenaline, a hormone that stops the body from caving</p><p>during moments of flight or fight, but can also give you a</p><p>burnout.</p><p>8. 8. Ovaries. We reach our final station—the ovaries. In addition to</p><p>holding the egg cells necessary for reproduction, the</p><p>ovaries</p><p>produce estrogen and progesterone under the hypothalamus’s</p><p>supervision, as well as testosterone.</p><p>By examining the HPG pathways and its crucial components, we can see</p><p>how this intricate system not only prepares the entire body to potentially</p><p>host a pregnancy but also supports a range of behaviors leading up to that</p><p>significant moment, from the sensation of butterflies in your stomach to</p><p>feeling energized during a romantic courtship. In addition, by acting upon</p><p>this system, estrogen in particular has been shown to boost metabolism,</p><p>protecting us against weight gain, insulin resistance, and type 2 diabetes.</p><p>Estrogen is also instrumental in maintaining bone health and in supporting</p><p>the heart by keeping blood vessels healthy, possibly by keeping tabs on</p><p>inflammation and cholesterol levels. On the downside, this connection is</p><p>also responsible for the many physical, or bodily, symptoms experienced</p><p>with the arrival of menopause. For instance, the risk of diabetes,</p><p>osteoporosis, and heart disease all increase after menopause. Yet for all the</p><p>good that estrogen does for a woman’s body, that’s nothing compared to</p><p>what it does for her brain. So on to the next, and much less appreciated,</p><p>brain-hormone route: inside the brain itself.</p><p>Route 2. The Brain-Estrogen Network</p><p>The neuroendocrine system doesn’t stop with the HPG. As shown in figure</p><p>6, it communicates with many other key regions of the brain, which are</p><p>referred to as the brain-estrogen network, as they are also susceptible to</p><p>estrogen levels. The most notable stops on Route 2 are:</p><p>Figure 6. The Brain-Estrogen Network</p><p>1. Limbic system and brainstem. The limbic system is buried deep</p><p>within the brain, snuggled just above the brainstem, which</p><p>connects our brains to the spinal cord running down the rest of</p><p>the body. Traced back to our evolutionary roots, these ancient</p><p>parts of the brain are trained on instinctive behaviors and</p><p>emotional responses. These impulses include stress, appetite,</p><p>sleep/wake, feelings, and nurturing instincts.</p><p>2. Hippocampus. This seahorse-shaped structure is considered the</p><p>memory center of the brain. Located in the limbic system, it is</p><p>responsible for forming episodic memories, or memories of</p><p>things you did in the past, like experiences from your childhood</p><p>or your first day at work. The hippocampus also creates</p><p>associations between our memories and our senses, connecting</p><p>summer with the smell of roses—while helping us learn new</p><p>things and aiding our sense of direction.</p><p>3. Amygdala. The hippocampus’s BFF, the amygdala, plays a central</p><p>role in emotional responses, including feelings like pleasure,</p><p>fear, anxiety, and anger. The amygdala also strengthens our</p><p>memories with emotional content.</p><p>4. Cingulate cortex and precuneus. These neighboring regions of the</p><p>brain’s cortical mantle are important for emotional processing,</p><p>learning, social cognition, and autobiographical memory. The</p><p>latter refers to our capacity to recall our personal history and</p><p>events, like what we did on a specific date at a specific time.</p><p>5. Prefrontal cortex. This is a super-evolved section of the brain that</p><p>helps us set and achieve goals. The prefrontal cortex assesses</p><p>information from multiple brain regions and adjusts behavior</p><p>accordingly. Doing so contributes to a wide variety of executive</p><p>functions, including focusing one’s attention, controlling</p><p>impulses, coordinating emotional reactions, and planning for the</p><p>future. A heavy hitter, the prefrontal cortex is also involved in</p><p>memory and language.</p><p>To summarize, the highly specialized HPG and brain-estrogen networks</p><p>ensure that our brains and ovaries are closely connected, on an hour-to-hour</p><p>basis, and that this connection has wide-ranging effects not only on the</p><p>body but also on our emotions, sensations, and ability to think and</p><p>remember. As a result, the health of the ovaries is linked to the health of</p><p>the brain, and the health of the brain is linked to the health of the ovaries.</p><p>Western medicine separated a woman’s brain and ovaries into different</p><p>disciplines and practices, but no woman in the world has the luxury of</p><p>separating them in her own body. The hormones flowing back and forth</p><p>between them spur these organs to develop as partners: they mature</p><p>together, cross milestones together, and in many ways, age together, too.</p><p>Thanks to just how far-reaching this interconnectedness is, any changes in</p><p>hormonal quantity and quality can profoundly affect not only a woman’s</p><p>reproductive health but also her physical and mental health.</p><p>THE FEMALE BRAIN RUNS ON ESTROGEN</p><p>Throughout the book, I am trying to reinforce the idea that there’s much</p><p>more to estrogen than fertility. Beyond its role in reproduction, this versatile</p><p>hormone is involved in a number of brain processes. That’s because the</p><p>brains of people born with ovaries, scientists have learned in recent</p><p>decades, are genetically engineered to respond preferentially to the estrogen</p><p>made by said ovaries.</p><p>As it turns out, day in and day out, estrogen molecules slide right into the</p><p>brain, searching for special receptors that are shaped precisely for this</p><p>hormone. The receptors are like tiny locks, waiting for the right molecular</p><p>key (estrogen) to turn them on. This is a vivid image for a crucial idea:</p><p>women’s brains are hardwired to receive estrogen. Once it arrives, estrogen</p><p>latches on to these receptors, activating a windfall of cellular activities in</p><p>the process. Loaded with these receptors, our brains are ready-made to be</p><p>estrogen-fueled.</p><p>A knowledge of this and of the workings of the neuroendocrine system</p><p>makes it easier to understand how menopause can set off such a wild</p><p>cascade of brain effects. If you’re a typical woman moving through your</p><p>forties or fifties, your lifetime egg supply is running out; as that happens,</p><p>the intricate, multi-hormone reproductive-signaling loop grows confounded,</p><p>its triggers altered by the biology of change. Meanwhile, as the brain and</p><p>ovaries start misreading each other’s demands for action, the brain</p><p>frantically cranks up estrogen production or accidentally drops the ball</p><p>instead, effectively throwing the brain-ovaries loop . . . for a loop.</p><p>Eventually the ovaries stop making estrogen, and what used to be a long-</p><p>term relationship comes to an end. The symptoms of menopause are then</p><p>the challenging consequences of a brain full of receptors, receiving less and</p><p>less of the fuel they need to take action.</p><p>It’s worth mentioning here that while women’s brains are wired to</p><p>respond to estrogen’s activation, men’s brains are similarly calibrated for</p><p>testosterone. This is important, as the quantity and longevity of each sex’s</p><p>activator hormone differ, and testosterone doesn’t generally run out until</p><p>late in life. This more gradual tapering-off process leads to andropause, the</p><p>male equivalent of menopause. However, as the tabloids remind us, most</p><p>men remain fertile until their seventies—which in a nutshell means that the</p><p>testosterone receptors in men’s brains have more time to adjust. Women’s</p><p>brains, on the other hand, don’t have that luxury.</p><p>As science has come to learn, the interaction between estrogen and</p><p>women’s brains is quite complex and easily disrupted. For starters, estrogen</p><p>itself isn’t as simple as it seems. The term “estrogen” actually refers to</p><p>estrogens—not a single hormone but a class of hormones with similar</p><p>functions. In chapter 3, I mentioned that the type of estrogen we measure in</p><p>blood is called estradiol. Estradiol is one of the main three types of</p><p>estrogen. The other two are called estrone and estriol.</p><p>Estradiol is the most potent and abundant type of estrogen during a</p><p>woman’s reproductive years and the principal growth hormone</p><p>required for reproductive development. It is produced mainly by the</p><p>ovaries, and its levels are markedly reduced after menopause.</p><p>Estrone is made by fat-rich adipose tissue and has a weaker effect</p><p>than estradiol. After menopause, estrone is the main type of</p><p>estrogen women’s bodies continue to produce.</p><p>Estriol is the estrogen of pregnancy. It is present in nearly</p><p>undetectable</p><p>amounts whenever one is not pregnant.</p><p>When doctors talk about estrogen, they are usually referring to the</p><p>combined effects of all three types. But when we’re talking about the</p><p>interaction of estrogen with our brains, we are talking mainly about</p><p>estradiol.</p><p>Estradiol: The Master Regulator of the Female Brain</p><p>Estradiol is so instrumental in a seemingly endless list of brain processes</p><p>that it has gained the title of master regulator of the female brain. I can’t</p><p>help but view estradiol as CEO of the Female Brain, Inc. It’s a genius</p><p>commander in chief who knows all aspects of the business, inside and out.</p><p>Estradiol’s most important functions include:</p><p>Neuroprotection. Estradiol plays a defensive role on our behalf by</p><p>boosting the immune system and imbuing brain cells with the ability</p><p>to overcome damage and aging.</p><p>Cell growth. Not only does estradiol protect the brain cells we</p><p>already have, but it helps grow new ones, while simultaneously</p><p>prompting cell repair and new connections throughout the brain.</p><p>Brain plasticity. Estradiol boosts the brain’s ability to respond and</p><p>adapt to all sorts of changes, from updating our neuronal networks</p><p>for learning and memory to preserving the brain’s ability to function</p><p>in the face of damage.</p><p>Communication. This hormone has its hands in many pies,</p><p>impacting multiple neurotransmitters, the brain’s chemical</p><p>messengers for signaling, communicating, and processing</p><p>information.</p><p>Mood. Estradiol has a positive effect on serotonin, a mood-</p><p>balancing chemical that promotes happiness and pleasure, not to</p><p>mention sleep. It also happens to be “nature’s Prozac,” delivering an</p><p>antidepressant effect system-wide.</p><p>Protection. Estradiol supports the immune system and protects the</p><p>brain from oxidative stress caused by harmful free radicals that can</p><p>foster illnesses like inflammatory disease, cancer, and dementia.</p><p>Cardiovascular health. Estradiol has positive effects on blood</p><p>pressure and circulation, protecting both brain and heart against</p><p>vascular damage.</p><p>Energy. This hormone also ensures that glucose, the brain’s main</p><p>meal, is efficiently burnt as energy. Consequently, when estradiol is</p><p>high, brain energy follows. By charging up brain function, estradiol</p><p>influences everything from mobility to our cognitive abilities.</p><p>So far, so good. However, after menopause, estradiol leaves. She</p><p>announces her retirement, firmly sets a course to wind down, and kicks up</p><p>her heels. Estrone is then promoted to the task. Unfortunately, estrone can’t</p><p>do what estradiol did. Without estradiol in town, the brain is driven to</p><p>distraction. The connections between neurons aren’t powered as efficiently</p><p>as before and tend to slow down. Over time, more connections are lost than</p><p>renewed. Brain cells experience more wear and tear with less access to</p><p>repair, which makes them age faster, too. Those happy and calming</p><p>chemicals that kept our systems balanced don’t show up as often as before.</p><p>It’s also more difficult to keep free radicals at bay, rendering the brain more</p><p>vulnerable to inflammation, aging, and a variety of medical conditions.</p><p>Bottom line, the loss of estradiol can be so impactful as to, at least</p><p>temporarily, scramble the mind’s once-successful choreography of thought,</p><p>emotion, and memory.</p><p>THE UPS AND DOWNS OF MENOPAUSE</p><p>The effects of estradiol’s mercurial behavior are particularly felt in the brain</p><p>regions powered by this hormone, which experience these effects firsthand.</p><p>The hypothalamus is the central node of this connection and takes the brunt</p><p>of the impact. Since this gland controls body temperature, an instability in</p><p>the supply of estradiol means that the brain can’t regulate body temperature</p><p>correctly. Remember the hot flashes? Scientists believe that’s the</p><p>hypothalamus going bonkers.</p><p>On top of losing hold over our internal temperature, the brain falters in</p><p>the regulation of sleep and wakefulness. The result: we have trouble</p><p>sleeping, with changes in our sleep rhythm and patterns. And since all these</p><p>brain regions are in communication, the issues between the two can</p><p>combine and whip up night sweats. The emotional amygdala or its</p><p>neighbor, the memory-minding hippocampus, take their turns, too—</p><p>prompting mood swings, forgetfulness, or both. The same goes with the</p><p>prefrontal cortex, in charge of thinking and reasoning. Maybe the fog rolls</p><p>in, and you have difficulty focusing or paying attention, or perhaps words</p><p>don’t come to mind as easily as they used to. And let’s not forget the</p><p>perpetual search for that elusive phone!</p><p>When we pull back the curtain on what’s going on inside the</p><p>menopaused-out brain, some of its more peculiar symptoms suddenly don’t</p><p>seem so strange anymore. The brain changes we reviewed at the beginning</p><p>of this book likely make more sense, too. They are a reflection of the</p><p>brain’s attempts to deal with the massive hormonal upheaval and</p><p>accompanying remodeling underfoot. They suggest that as the brain is busy</p><p>trying to cope with the consequences of the loss of estradiol, its defense</p><p>mechanisms are temporarily lowered. The powerful shifts in brain</p><p>chemistry and metabolism may then prompt the symptoms of menopause,</p><p>while also rendering some women’s brains more vulnerable to a variety of</p><p>medical stresses such as depression and cognitive decline.</p><p>With all that said, there’s more to menopause than its downsides. In fact,</p><p>we’ve finished reviewing what could go wrong with menopause. It’s time to</p><p>explore what could go right.</p><p>First off, menopause is a window not only of vulnerability but also of</p><p>opportunity, as it provides a critical time to detect any signs of medical risk</p><p>and to intercede with strategies to reduce or altogether prevent that risk. By</p><p>knowing when to look (during menopause) and what to look for (the brain</p><p>changes and symptoms that can ensue), we can not only validate women’s</p><p>experience of menopause but also address what to do about it. Taking better</p><p>care of our brains during these years will serve both to bring the symptoms</p><p>of menopause under control and to dramatically reduce any potential risk of</p><p>future issues.</p><p>Just as important, while many women are vulnerable to neurological</p><p>shifts during menopause, the majority of the female population gets through</p><p>this transition without developing severe long-term problems. As we</p><p>discussed in the previous chapter, symptoms like brain fog and hot flashes</p><p>tend to ease and eventually fade away a few years into menopause.</p><p>Personally, these considerations changed my approach to menopause and</p><p>the focus of my research. Like most other scientists, when I started</p><p>researching menopause, my initial goals were to understand the symptoms</p><p>and health risks that menopause can bring about. I was looking for all sorts</p><p>of things that could go wrong—energy declines, the loss of gray matter,</p><p>Alzheimer’s plaques . . . all the baddies for which we wanted to find</p><p>solutions. After all, entire bodies of literature portray menopause as a</p><p>medical mess. But if menopause was such a catastrophe, no woman would</p><p>be able to remain functional for another thirty years and beyond. So, my</p><p>team and I set out to investigate.</p><p>We enrolled more participants and did even more brain scans. We</p><p>gathered our data and sifted through it, determined to take in the bigger</p><p>picture. Over time, as we dug deeper and broadened our sights, we learned</p><p>about the good of menopause—not just the bad and the ugly that’s been the</p><p>takeaway thus far. What we discovered is a broader and bolder story, one</p><p>that in many ways turns out to be encouraging. I will share more about this</p><p>in the next chapters, but for now, I want to show you some of our recent</p><p>work providing evidence that menopause isn’t all about vulnerability.</p><p>If you recall from chapter 1, our first discovery was that brain energy</p><p>declines during the menopause transition. I am happy to report that we’ve</p><p>made significant progress since those first before-and-after scans were</p><p>taken. By expanding our studies both in size and duration, we found that, in</p><p>some brain regions at least, the energy changes appeared to be temporary.</p><p>For instance, while brain energy showed a dip during perimenopause and</p><p>early postmenopause, its levels stabilized or improved years later. As shown</p><p>in the figure below, some parts of the brain even showed a refreshing</p><p>rebound in energy during the late postmenopausal stage, which starts</p><p>approximately four years after the final menstrual period. Check out the</p><p>arrows pointing to the frontal cortex below. Remember, this is the brain’s</p><p>thinking and multitasking area.</p><p>Figure 7. Brain Energy Changes from Premenopause to Late Postmenopause</p><p>The menopause story brightened further with a late but lovely</p><p>postmenopausal recoup in the brain’s gray matter. While gray matter tends</p><p>to decline from the premenopausal to the postmenopausal stage, in some</p><p>brain regions, this change appeared to plateau for quite a few women once</p><p>menopause was completed. This also correlated with better memory after</p><p>menopause. Do you remember how memory can decline during</p><p>perimenopause, returning to close-to-baseline levels later on? Our data are</p><p>right in synch with this timeline.</p><p>It’s important to underline that these are recent findings, all in the process</p><p>of being confirmed on a global scale to reach firm and exact conclusions.</p><p>While we work to make this happen, my takeaway is that menopause is a</p><p>dynamic neurological transition that reshapes the landscape of the female</p><p>brain in unique ways. There are hints and glimmers that this reshaping may</p><p>include adaptations that help compensate for and maintain brain function,</p><p>despite the drop in estrogen. In other words, the ovaries may close up shop,</p><p>but the brain has its ways of carrying on. Many lines of evidence indicate</p><p>that women’s brains have the remarkable, much underestimated, yet-to-be-</p><p>celebrated ability to adapt to menopause. This information is just the</p><p>beginning of unlocking menopause’s secrets and upgrading our experience</p><p>of this important milestone in every woman’s life.</p><p>6</p><p>Putting Menopause in Context: The</p><p>Three P’s</p><p>PUBERTY, PREGNANCY, AND PERIMENOPAUSE</p><p>As women, we are used to dealing with hormonal changes. Whether it is</p><p>puberty, your monthly cycle, the postpartum period, perimenopause, or</p><p>postmenopause, we experience the ups and downs of hormones for most of</p><p>our lives. So now that we’ve reviewed the neuroendocrine system and its</p><p>star hormones, let’s talk about the peak life transitions that distinguish that</p><p>system and their interconnectedness. Many women go through a trio of</p><p>these stages in their lives. I like to refer to them as the Three P’s: puberty,</p><p>pregnancy, and perimenopause. These turning points represent moments</p><p>when our brains and hormones meet and morph in a uniquely female way.</p><p>While we’re all familiar with the idea that our bodies change with these</p><p>transitions, it’s not as obvious how much our brains have to do with them,</p><p>too. Here’s a preview.</p><p>Estrogen levels balloon during puberty, plateau as we enter adulthood,</p><p>and fluctuate with every menstrual cycle, only to peak once again if one</p><p>gets pregnant. More precisely, hormonal fireworks occur every time a</p><p>woman is pregnant, dipping dramatically once the baby is born. Hormone</p><p>levels rise again afterward, steering a more or less steady course until</p><p>reaching the most turbulent of the big P’s: perimenopause. Eventually</p><p>perimenopause passes, too, and estrogen recedes, while other hormones</p><p>increase instead. We often visualize this hormonal activity as ovary-driven,</p><p>but our brains would beg to differ. Throughout all these years, our brains</p><p>are buckled in beside our ovaries on a serious hormonal roller coaster,</p><p>making for a just as serious mind-body ride.</p><p>In fact, the Three P’s are like three peas in a pod; they are part of a</p><p>continuum and have a lot in common. Looking at their commonalities is</p><p>particularly helpful to put menopause in context. When we do, we see</p><p>menopause isn’t as alien an event as we’ve been conditioned to believe but</p><p>rather another stage of a woman’s reproductive and neurological journey.</p><p>Moreover, when we view each of these stages the way brain scientists do,</p><p>we notice that they each represent a time of vulnerability (manifesting as</p><p>symptoms and medical risks) and resilience (including symptom recovery</p><p>and personal growth). As we explore the latest science on the Three P’s, let</p><p>us remember this age-old adage: Every rose has its thorn.</p><p>THE BRAIN FROM BIRTH THROUGH PUBERTY</p><p>Most people think a newborn’s brain is like a blank slate, ready for the</p><p>world to write upon it. According to a large body of scientific evidence,</p><p>however, that’s not entirely the case. Brain development, prompted by our</p><p>DNA, starts in utero, kicking off before we’re born. Fun fact: At first, all</p><p>children’s brains appear exactly the same—female. Yes, you heard right.</p><p>Female is nature’s default brain setting. (Take that, too, Darwin.) It’s only</p><p>after a surge in testosterone that boys’ brains begin to take on male</p><p>attributes, which, if you recall from the previous chapter, means they</p><p>become wired to respond more to testosterone.</p><p>Over time, estrogen and testosterone play an essential role in the sexual</p><p>differentiation of the brain, as the structures belonging to the</p><p>neuroendocrine system begin to differ somewhat between the sexes in their</p><p>anatomical structure, their chemical makeup, and even in their reactions to</p><p>stressful situations. While these differences do not dictate sexual</p><p>preferences or behavior, they are important, as they influence the way our</p><p>brains mature and eventually age.</p><p>At birth, a child’s brain contains 80 to 100 billion nerve cells, while new</p><p>connections between neurons develop at the explosive rate of up to 2</p><p>million per second, prompting the brain to quickly almost double in</p><p>volume. After this impressive upsurge, brain density has reached its max</p><p>and begins to decrease. A process of refinement and reduction sets in as the</p><p>brain starts to respond to life experiences and the world around us. Pruning</p><p>is the process by which a deep restructuring occurs as the most used</p><p>connections between cells strengthen and take hold and those that are less</p><p>essential die off. In a perfect example of “use it or lose it,” many of the</p><p>brain’s original neurons are discarded, while many more multiply and grow</p><p>as the child starts engaging with the environment. Keep this process in mind</p><p>—it is very important to understand menopause as well.</p><p>By age six or seven, this elaborate dance of growth and elimination</p><p>becomes evident outwardly as the child masters new cognitive capacities</p><p>like reading, tying their shoes by themselves, socializing, and much more.</p><p>At this point, the brain has reached approximately 90 percent of its full size,</p><p>and with it, a certain stability in behavior. However, even though it may not</p><p>grow much size-wise afterward, it is far from done maturing. In fact, most</p><p>brain regions are still in a state of growth and change, a process that peaks</p><p>just in time for the first P on our list—the pimple-faced period of emotions</p><p>run wild: Puberty with a capital P!</p><p>HOW PUBERTY CHANGES THE BRAIN</p><p>When we hit puberty, the doors fly open at hormone central. During this</p><p>time, boys’ bodies produce significantly more testosterone than girls’, while</p><p>girls’ bodies shift into a higher estrogen-to-testosterone ratio. These</p><p>hormonal surges provoke the body to develop into its adult form, complete</p><p>with a mature reproductive system. But more is going on than this. This</p><p>very same hormonal turmoil is also priming the brain for both growth and</p><p>new forms of learning.</p><p>What may come as a surprise is that instead of the brain continuing to</p><p>grow in size as it matures, it literally shrinks during puberty. The neuron-</p><p>pruning process goes into overdrive once sexual maturation is reached:</p><p>about half of the brain’s original neurons are shed, and their connections are</p><p>dramatically scaled back. While this downsizing can appear counterintuitive</p><p>at first glance, it is not only normal but necessary. It’s all about the brain</p><p>becoming leaner and meaner, and more efficient overall. Keeping neurons</p><p>alive and functioning requires a tremendous amount</p><p>of energy, so ideally,</p><p>the brain strives to achieve its goals with as few neurons as possible,</p><p>working smarter, not harder. This is also how the brain begins to automate</p><p>specific actions. For example, a teenager can tie her shoes and ride a bike</p><p>automatically. The neurons initially responsible for breaking down and</p><p>directing these skills in steps appropriate for a toddler are no longer</p><p>necessary and can be discarded. The phrase “It’s just like riding a bike” is</p><p>apropos here. Hence, this system consolidation clears out the old and makes</p><p>room for the new in one fell swoop.</p><p>This process is, however, not particularly straightforward, with changes</p><p>developing at varying rates across different parts of the brain. There’s an</p><p>important back-to-front mismatch in brain development: the amygdala and</p><p>hippocampus, which are in charge of emotion and memory, kick into high</p><p>gear early on. The prefrontal cortex—the area in charge of controlling</p><p>impulses and executive skills, like being self-possessed enough to say, “I’d</p><p>better not do that”—is late to the party. Since adolescents are working with</p><p>a frontal cortex still under construction, their self-control is not as</p><p>accessible as their parents might wish, giving us a peek under the hood</p><p>regarding the tumultuous moments of recklessness and moodiness of the</p><p>teenage years. Never fear; this, too, shall pass. As the prefrontal cortex</p><p>further develops, teens become better equipped to resist impulses and assess</p><p>potential risks. At the same time, they develop the ability to put themselves</p><p>in another person’s shoes, a capacity that is often called theory of mind, or</p><p>mentalizing. This uniquely human superpower allows us to understand</p><p>other people’s intentions and beliefs. In doing so, we can extrapolate from</p><p>this data to understand and predict behavior while also better integrating</p><p>ourselves into society. Today, scientists attribute this remarkable capacity to</p><p>the puberty-fueled brain revamp. (Hint: This perspective also provides us</p><p>with a preview of what lies ahead with the next two P’s.)</p><p>Interestingly, the brain maturation timeline is somewhat different for</p><p>boys and girls, hitting peak production when children approach sexual</p><p>maturity, which is around age eleven for girls and fourteen for boys.</p><p>Perhaps as a result, adolescent girls tend to exhibit earlier and stronger</p><p>connections between the impulsive amygdala and the cautious-minded</p><p>frontal cortex than their male counterparts. Whether due to nature, nurture,</p><p>or both, these differences have been interpreted as evidence that girls</p><p>mature faster than boys, showing a slight advantage in theory of mind tasks,</p><p>empathy, social competence skills, and social understanding. They also</p><p>show better communication abilities, learning to speak at an earlier age and</p><p>generally reaching a greater fluency—a difference that can persist</p><p>throughout the lifespan. Lest we fall into stereotyping, let’s be clear: We</p><p>don’t review this data to fuel a competition but to better understand</p><p>women’s natural strengths and comprehend how these abilities might</p><p>develop early in life and then be impacted by aging and reproductive</p><p>changes. Because sure enough, although exciting new skill sets are being</p><p>forged, there is a price to pay.</p><p>The “Period Brain”</p><p>Puberty marks the onset of the menstrual cycle, which can profoundly alter</p><p>the circuitry of a teen girl’s brain, impacting the way she thinks, feels, and</p><p>acts on a monthly basis. The notion that a woman’s cycle can befuddle her</p><p>brain is a main staple of popular culture. Dismissive and often derogatory</p><p>statements like “She must be PMS-ing” are by now part of the everyday</p><p>vernacular. As unsympathetic as these expressions can be, many women do</p><p>experience a vulnerable side during their period. But while that’s made it</p><p>into society’s wry water-cooler rhetoric, the flip side has not. The “period</p><p>brain” is not all bad news.</p><p>Thanks to an incredibly complex neurological phenomenon, the brain’s</p><p>size, activity, and connectivity shift monthly, if not weekly, in synch with</p><p>our cycle. While these brain micro-cycles are generally subtle, they are</p><p>quite real. For example, when estradiol runs higher during the first half of</p><p>the month, brain cells visibly sprout new spines that reach out and connect</p><p>with other cells, striking up sharpened neuronal conversations near and far.</p><p>The amygdala and hippocampus swell appreciably in size, and their</p><p>connections with the prefrontal cortex appear to get stronger—which has</p><p>been linked to better executive skills and helps us feel more focused and</p><p>overall more on. Certain cognitive skills are also heightened at this time,</p><p>such as verbal fluency, communication, and social responsiveness.</p><p>On the flip side, as estradiol recedes during the second part of the cycle,</p><p>some connections between neurons also recede. This has been linked to low</p><p>mood, irritability, headaches, and even fatigue or sleepiness for some</p><p>women, while others can feel sad or tearful. These monthly back-and-forths</p><p>are important to consider because they clarify the very nature of the brain-</p><p>hormone connection during our reproductive life, while also giving us a</p><p>preview of what our nonreproductive life might be like, once the menstrual</p><p>cycle has ended for good. Additionally, the surging hormones of puberty</p><p>and their fluctuations during a girl’s monthly period can render her brain</p><p>more vulnerable to stress, anxiety, and moodiness. It’s telling that the</p><p>prevalence of depression, anxiety, and eating disorders shifts from being</p><p>equal between girls and boys before puberty to a 2:1 female-to-male ratio</p><p>afterward. Moreover, one out of four women suffers from clinical PMS, a</p><p>condition characterized by irritability, tension, depressed mood, tearfulness,</p><p>and mood swings at specific times of the month. Symptoms are often mild,</p><p>but sometimes they can be severe enough to affect daily activities</p><p>substantially.</p><p>THE ADULT FEMALE BRAIN</p><p>As the adolescent years make way for adulthood, the brain continues to</p><p>mature, and its streamlining process continues well into our twenties. The</p><p>prefrontal cortex also further develops at this stage, a nod to twenty-one</p><p>being the minimum legal age in the United States to purchase alcohol.</p><p>Whether it’s maintaining one’s first credit line or keeping a plant alive for</p><p>more than a few weeks, many of us find that we are now more capable than</p><p>we thought and possess better judgment than ever before, as our brains</p><p>master the ability to look ahead.</p><p>Women’s brains in particular come into adulthood gifted with an</p><p>excellent ability to recall specific aspects of verbal information, such as the</p><p>precise details of a conversation, as well as episodic memory—the ability to</p><p>recall details of past personal experiences, chiefly what, where, and when</p><p>they happened. This fact may explain how so many women seem to possess</p><p>crystal clear recall of conversations their husbands swear never occurred!</p><p>All kidding aside, young adult women come equipped with a mature brain,</p><p>a sharp memory, and fluent communication skills. At the same time,</p><p>though, the internal processes that make and remake the brain (namely, the</p><p>death and birth of neurons and their fluctuating activity) will rise and fall</p><p>with each of our menstrual cycles, and throughout our lives. In fact, even</p><p>once the brain has reached its mature state, it remains plastic, retaining the</p><p>capacity to shift and change in response to our life experiences. These</p><p>brain-body shifts are never more evident than... when a woman becomes</p><p>pregnant.</p><p>Now, a word about pregnancy. Not all of us choose this path, I’m aware,</p><p>instead directing our courage and magic elsewhere. I hope that each of us</p><p>will be lauded for our signature shine in due course. For the purposes of this</p><p>chapter, I speak to the potential of motherhood, a deeply unsung role that</p><p>needs to garner the proper respect. To my mind, the most significant</p><p>contribution that science can provide is to highlight how pregnancy and</p><p>motherhood change the female brain in ways that, while rendering us</p><p>vulnerable to some extent, release in</p><p>to guide us forward. So women of my generation felt unseen</p><p>and unheard by healthcare professionals who weren’t educated in this space</p><p>and didn’t have the research to help guide us through the confusing, often</p><p>chaotic symptoms we were experiencing. Instead, we weathered the</p><p>turbulence, while living in a culture that intimated women at midlife were</p><p>prone to going crazy. This book is testimony to progress.</p><p>A few years ago, I was honored to write the foreword to Lisa’s book The</p><p>XX Brain, and now I am thrilled to write the foreword to this book as well.</p><p>In The Menopause Brain, you have the most current science and the best</p><p>practical guidance available, and it comes from a researcher who is not only</p><p>an innovative and visionary thinker but someone I now consider a friend for</p><p>life.</p><p>I first met Lisa in 2017, when I was looking for research to help answer</p><p>the questions of why women are twice as likely to develop Alzheimer’s as</p><p>men, and why women of color are at even higher risk for the disease.</p><p>Finding almost no research available motivated me to start my nonprofit</p><p>organization, the Women’s Alzheimer’s Movement (WAM), and it has</p><p>driven my quest ever since to learn about women’s brains throughout the</p><p>lifespan. Meeting Lisa along this journey was a game changer. She was one</p><p>of the first scientists to show the impact of menopause on a woman’s brain</p><p>at midlife, and to discuss the brain’s response to menopause in general. Lisa</p><p>had just published the first study showing that women’s brains become</p><p>more vulnerable to Alzheimer’s in the years before and after menopause.</p><p>She was among the first researchers who not only described how a woman’s</p><p>brain changes physically and shrinks during menopause, but developed the</p><p>technology and research to show the process in action. Thanks to Lisa and</p><p>other like-minded scientists dissatisfied with the lack of research on</p><p>women’s brain health, a movement began that aimed to study the unique</p><p>impact of sex hormones such as estrogen on women’s health. I was</p><p>delighted to help fund some of that research through the WAM Research</p><p>Grants, which are awarded to scientists looking at the role of gender as a</p><p>risk factor for Alzheimer’s.</p><p>It’s a sad fact that despite the prevalence of menopause symptoms and its</p><p>potentially serious consequences on long-term health, research into</p><p>menopause has historically been underfunded and overlooked, right</p><p>alongside women’s health in general. For Black women in particular, the</p><p>health consequences of this oversight are even more dire, and the road</p><p>through menopause often longer and harder. There is no excuse for</p><p>ignorance.</p><p>My mission now is to make up for lost time, for the neglect in funding</p><p>that has led to a historic gap in our understanding of women’s health. It’s</p><p>why in 2022 we joined forces with one of the world’s top-rated healthcare</p><p>systems to become WAM at Cleveland Clinic. I’m proud to say WAM</p><p>remains the preeminent organization for women and Alzheimer’s, made all</p><p>the stronger by now having partners leading the field in medical research</p><p>and excelling at delivering the best clinical care available. In 2020 we made</p><p>history together when we opened the first Alzheimer’s Prevention Center</p><p>designed just for women at the Lou Ruvo Center for Brain Health in Las</p><p>Vegas. Now we are working on a shared mission to make Cleveland Clinic</p><p>a premier holistic center for women’s healthcare where every patient feels</p><p>seen and heard.</p><p>My focus is on continuing to support all those around the world who, like</p><p>Lisa, are researching what is happening to women’s brains during midlife,</p><p>while also ensuring that women everywhere get the valuable information</p><p>they need to take control of their health during these critical decades. And</p><p>it’s not just women who need to have this information but their doctors,</p><p>friends, and families as well. This book is a guide for us all, and I hope it is</p><p>studied by those teaching medicine and those practicing it. I encourage</p><p>women to remember that they can make a difference to their own health. I</p><p>hope they will visit their healthcare providers with this book and its</p><p>research in hand, and together formulate a plan that will deliver them the</p><p>best medical care they need and deserve to set them up for lifelong health.</p><p>So empower yourself with this knowledge, share it with women you meet</p><p>along the journey. Become what I call an “architect of change”—someone</p><p>who brings about the change they want to see in the world. Your brain is</p><p>your biggest asset. Care for it well so it may last a lifetime. I promise it will</p><p>be the best investment you can make in your future health.</p><p>—Maria Shriver</p><p>PA RT 1</p><p>THE BIG M</p><p>1</p><p>You Are Not Crazy</p><p>“AM I LOSING MY MIND?”</p><p>Between the ages of thirty and sixty, many women will wake up one</p><p>morning and wonder what hit them. Whether it’s uncontrollable sweating or</p><p>a barrage of brain fog and anxiety, any one of us can be confronted with an</p><p>onslaught of peculiar changes sudden enough to, quite literally, make her</p><p>head spin.</p><p>It might be a sense of disorientation, where you find yourself doing</p><p>increasingly absent-minded things, like entering a room only to wonder</p><p>what made you go there in the first place. Belongings may be misplaced,</p><p>with milk cartons finding their way into cabinets and cereal boxes ending</p><p>up in the fridge. Communication can also become a challenge. Moments of</p><p>sheer panic may arise as you struggle to come up with that word on the tip</p><p>of your tongue or draw a blank on something you just said, losing your train</p><p>of thought. Emotions, too, can be all over the place, as if a heavy darkness</p><p>is causing you to weep for no clear reason—only to be replaced a moment</p><p>later by waves of irritability or even anger. And just when you hoped a good</p><p>night’s sleep might resolve these issues, sleep becomes elusive. Like a</p><p>fickle ghost, it visits sporadically throughout the night, or may not appear at</p><p>all. With the rapid-fire onset and the intensity of these unexpected changes,</p><p>it’s no wonder many feel as if their own bodies are betraying them,</p><p>throwing any woman into a tailspin of questioning herself, her health, and</p><p>even her sanity.</p><p>Perhaps you don’t recognize any of these symptoms—yet. Most likely,</p><p>though, you’ve heard about them before. From girlfriends, from your</p><p>mother, from googling late at night when you can’t sleep... again.</p><p>We now have a name for it: menopause brain.</p><p>More often than not, the answer to the phenomena so many women</p><p>experience in midlife is nothing more, but also nothing less, than</p><p>menopause.</p><p>Menopause is one of the best-kept secrets in our society. Not only has</p><p>there been no proper education or culture of support around this rite of</p><p>passage common to all women, but often, menopause isn’t even discussed</p><p>within families. What’s noteworthy is that even when there is some</p><p>information or wisdom that’s shared, it’s generally not centered around the</p><p>most prominent aspects of the transition—namely, how menopause impacts</p><p>the brain.</p><p>As a society, insofar as we have understood menopause at all, it’s</p><p>generally only half of what it’s all about—the half that pertains to our</p><p>reproductive organs. Most people are aware that menopause marks the end</p><p>of a woman’s menstrual cycle and, therefore, her ability to bear children.</p><p>But when the ovaries close up shop, the process has far broader and deeper</p><p>effects than those associated with fertility. Far from the spotlight,</p><p>menopause impacts the brain just as much as it impacts the ovaries—</p><p>directly and powerfully, and in ways we are only beginning to gather real</p><p>data about.</p><p>What we do know is that all these baffling symptoms—the heat surges,</p><p>the feelings of anxiety and depression, the sleepless nights, the clouded</p><p>thoughts, the memory lapses—are, in fact, symptoms of menopause. The</p><p>real kicker, however, is that they don’t originate in the ovaries at all. They</p><p>are initiated by another organ entirely: the brain. These are, in fact,</p><p>neurological symptoms that come from the ways that menopause changes</p><p>the brain. As much as your ovaries have their role in this process, it’s</p><p>us an as-yet-unrecognized resilience.</p><p>Understanding that each of the Three P’s carries both vulnerabilities and</p><p>resilience is key to understanding and accepting not just menopause but</p><p>womanhood as a whole.</p><p>HOW PREGNANCY CHANGES THE BRAIN</p><p>The journey of becoming a mother is undoubtedly one of the most</p><p>monumental experiences a person—and a body—can have. A slew of</p><p>changes occur, many immediately apparent: bellies are growing, breasts are</p><p>as well, and morning sickness might disturb you far past noon. But all these</p><p>changes belie an essential fact: bringing a new life into the world impacts</p><p>your brain just as much as it does the rest of you. Once again, your</p><p>hormones exert as powerful an influence on the inside as on the outside.</p><p>Estrogen and progesterone rise enormously, ballooning fifteen to forty</p><p>times beyond their usual levels. Oxytocin, affectionately coined the love</p><p>hormone, enters the mix, too. And if you recall, the brain is involved in the</p><p>making of all of these hormones and is impacted by them in return. As a</p><p>result, a woman’s brain may change more quickly and drastically during</p><p>pregnancy and postpartum than at any other point in her life, including</p><p>puberty. However, much like what happens in puberty, while your body is</p><p>growing, your brain is downsizing.</p><p>Research demonstrates that pregnancy is marked by extensive reductions</p><p>in the brain’s gray matter. In the most comprehensive study so far,</p><p>researchers did brain scans on twenty-five first-time mothers before they</p><p>became pregnant and then again during the first few weeks after giving</p><p>birth. Their gray matter had shrunk so consistently that a computer</p><p>algorithm could predict with complete accuracy whether a woman had been</p><p>pregnant just by looking at her brain!</p><p>The scientists were so puzzled by these findings that they decided to peek</p><p>inside the workings of the moms’ brains in a different way—by showing</p><p>them pictures of their infants. The data showed a compelling revelation.</p><p>Several of the same brain areas that had lost gray matter during pregnancy</p><p>were the very ones that responded with the most boisterous brain activity to</p><p>photos of the mom’s own baby as opposed to photos of other infants. After</p><p>all aspects of the data had been reviewed, it became clear that the more</p><p>profound the decrease in gray matter during pregnancy, the stronger the</p><p>bond between mom and baby after giving birth. As odd as these results may</p><p>seem, there’s a reasonable explanation. If we look at this from the brain’s</p><p>perspective, pregnancy isn’t too dissimilar from puberty. Remember that</p><p>during puberty, surges in sex hormones cause a loss of gray matter, as</p><p>unnecessary brain connections are pruned, a process that sculpts the teen’s</p><p>brain into its adult form. This loss precipitates a gain: maturation. A teen’s</p><p>smaller brain simply reflects more streamlined brain circuitry. Scientists</p><p>believe that pregnancy triggers a comparable development. As certain links</p><p>between neurons drop away to encourage the formation of new, more</p><p>valuable connections, the brain becomes leaner to get meaner all over again.</p><p>This is how I like to think about it: For those skills that have become</p><p>second nature (doing basic math, cooking, driving), the brain no longer</p><p>needs to hold the neuronal space to support them. This “automatic pilot”</p><p>function allows the brain to dump what’s superfluous and refurbish new</p><p>mental pathways—those that will allow new moms to better respond to</p><p>motherhood’s myriad demands and urgencies. Sure enough, in the above</p><p>study, another round of brain scans done two years after childbirth showed</p><p>that the gray matter loss stuck around in some parts of the brain, but the</p><p>hippocampus and amygdala had actually grown back, their size returning to</p><p>pre-pregnancy levels. The frontal cortex also displayed a similar restoration.</p><p>These regions’ functionality was also off the charts. Take the amygdala in</p><p>particular, which is involved in experiencing love and affection but also acts</p><p>as a generator of the motivations and emotions that govern parental</p><p>instincts, everything from nursing and protecting one’s child to the impulse</p><p>to engage and play with them. While the passage of puberty was about</p><p>balancing instincts with rationality, pregnancy pivots us back toward our</p><p>instincts instead, designating renewed space in which to activate them—and</p><p>give them the credit they deserve.</p><p>The Supermom Brain</p><p>Though moms are rarely caught wearing star-spangled capes or wielding</p><p>magic shields, one worth her salt rates superhero status in my book. As the</p><p>days, weeks, and years roll on, many new mothers realize how quickly they</p><p>acquire an impressive arsenal of skills many never knew existed pre-</p><p>motherhood. These superpowers are not only near universal but</p><p>scientifically proven. For starters, one of the first skills you develop as a</p><p>new mom is a heightened sense of smell. No, we’re not joking about dirty</p><p>diapers here. According to the studies, almost 90 percent of new mothers</p><p>can recognize their little ones by scent thanks to a primal connection our</p><p>brains establish with our babies. Although you probably have not had to</p><p>pick your baby out of a lineup while blindfolded, rest assured, you would</p><p>actually be able to. Your brain knows what to do.</p><p>Let’s move on to the “love spell.” This magic is mom’s new aptitude to</p><p>release copious amounts of oxytocin, especially during nursing and skin-to-</p><p>skin time. This huggy hormone prompts the uterus to contract during</p><p>childbirth before teaming up with prolactin to cue breast milk production.</p><p>At the same time, this boost in oxytocin has a strong effect on the brain’s</p><p>emotional centers, compelling a new mom to be smitten with her baby, and</p><p>vice versa, in ways that words fail to describe. The surge in oxytocin</p><p>combines with that in another hormone, called vasopressin, prompting a</p><p>very primitive instinct called maternal aggression to kick in. This term</p><p>refers to the “mama bear” behavior a mother manifests in defending her</p><p>offspring against threats, which is powered by a brand-new “mama bear</p><p>brain” that contains a virtual GPS for tracking and protecting the child at all</p><p>times. We’ve all done it. There might be five other kids in the sandbox with</p><p>a purple onesie on, but every mom has the uncanny ability to scan and spot</p><p>her own purple-onesie-wearing tot in a matter of seconds and run to the</p><p>rescue. We are also instilled with the adrenaline and wherewithal necessary</p><p>to draw a line in the sand(box), if need be, completing our task with</p><p>aplomb. The adrenaline rush, once again, starts in the brain.</p><p>The genius doesn’t stop there. Perhaps the most important upgrade is that</p><p>the brain regions impacted by pregnancy are involved in the theory of mind,</p><p>just as with puberty. This is a mom-specific longer-term spinoff of what we</p><p>were discussing above—a heightened ability to see and recognize other</p><p>people’s mental states, feelings, and nonverbal cues, anticipating needs and</p><p>probable reactions. Whether it’s interpreting a baby’s body language or her</p><p>various cries and coos, being able to understand what is going on in</p><p>someone else’s head, especially when there are no words, comes in handy.</p><p>When these cognitive skill sets light up, we can better form attachments to</p><p>others—a key to developing closeness with our child and within our family</p><p>structure. As a most helpful add-on, many moms discover that they can</p><p>quite literally read minds via a sixth sense. Moms just know when</p><p>something bad might be going down with their child because they just feel</p><p>something isn’t right—a combination of maternal instincts, a motherly</p><p>spidey sense, and being around each other so much. Moms notice things</p><p>they’d never pick up on in any other human—to the point that they can</p><p>often predict their children’s needs before tears flow or a fever breaks.</p><p>Motherhood is certainly among the most complex and demanding set of</p><p>circumstances one can experience in life. Not only do our bodies need to go</p><p>through a metamorphosis to grow and nurture a new human, but so do our</p><p>priorities and day-to-day lives. Our brains intuitively,</p><p>or more likely by</p><p>design, understand this and alter themselves in the process. The good news</p><p>is that pregnancy prompts brain changes that boost critical maternal</p><p>instincts and conceivably strengthen social cognition skills simultaneously.</p><p>The bad news is that the upgrade your brain just downloaded can come at a</p><p>cost. The same brain morph that delivered shiny new features can also</p><p>rearrange your memory and attention files, trigger changes in mood, and</p><p>roll out a steep learning curve to our new operating system.</p><p>“Momnesia,” the Baby Blues, and Postpartum Depression</p><p>The frowned-upon “mommy brain,” aka “baby brain” or “momnesia,”</p><p>refers to a spacey, somewhat altered state where one may become more</p><p>forgetful or scatterbrained. Whatever you call it, if you’re a mother, you can</p><p>probably relate. Combine equal parts hormonal changes and the extensive</p><p>rewiring that is taking place inside your brain, plus a good dose of stress</p><p>and sleep deprivation, and boom—over 80 percent of pregnant women</p><p>perceive a decline in cognitive function. These changes persist postpartum,</p><p>with almost half of all new mothers experiencing forgetfulness, a narrowed</p><p>focus, and brain fog for months after giving birth. This makes sense</p><p>considering that the mommy brain maintains its new, kid-centric</p><p>architecture for at least two years post-birth. These sensations may cause</p><p>new moms to feel that their brains aren’t functioning as they were pre-baby.</p><p>Multiple studies indicate that some cognitive skills, memory first and</p><p>foremost, can indeed be impacted by pregnancy and postpartum. Such</p><p>functions include chiefly multitasking and “spatial memory” (the ability to</p><p>recall where things are). For example, when you navigate your local</p><p>grocery store each week, your spatial memory enables you to make a</p><p>beeline to your favorite coffee without searching the entire store. However,</p><p>if you find yourself having to do a double take as to where the coffee aisle</p><p>even is, you can blame it on mommy brain.</p><p>What do we make of this?</p><p>First off, pregnant women and new moms aren’t making stuff up. At</p><p>some point, it’s common to feel like your little bundle of joy has not only</p><p>hijacked your body but taken off with your mind, too. So kudos for keeping</p><p>your cool in the process. Second, and most important, these changes are</p><p>temporary, effectively resolving over time. Third, studies have shown that</p><p>even though many expectant women and new moms don’t feel as mentally</p><p>sharp as they used to, their IQ is unquestionably unaltered. As troubling as</p><p>they might feel, these slipups manifest themselves mainly as minor memory</p><p>lapses or brain fog, which can mess with our usual perception of ourselves</p><p>but are in no way an illness. (Note how similar this experience is to</p><p>perimenopausal brain fog.) For those who can’t shake off the worry, there is</p><p>no evidence these mental blips might be linked to a higher risk of dementia.</p><p>The foggy mental state associated with pregnancy and postpartum is</p><p>likely a transitory trade-off for the new, highly specialized brain in bloom.</p><p>Consider it sort of like growing pains. In effect, cognitive slips are likely a</p><p>result of a change in priorities at a neurological level. Life is operating</p><p>according to a new set of rules and requirements, and so are you and your</p><p>brain. The fact that it can also be wonderful and rewarding doesn’t render it</p><p>any less challenging. Experts believe that the maternal brain becomes so</p><p>intensely focused on the safety and needs of the child as to necessitate that</p><p>other daily activities take a back seat. Forgetting to pick up milk or to put</p><p>the laundry in the dryer is frustrating, but remembering 3:00 A.M. feedings</p><p>and managing to mentally note and respond to the intricate web of a</p><p>newborn’s varying needs is the priority. More disconcerting is that fulfilling</p><p>this new job description can go largely unnoticed, seen as expected or taken</p><p>for granted—while not ticking off the boxes on the old list seems to garner</p><p>more attention.</p><p>As a scientist and a mother, I find the idea almost laughable that new</p><p>moms suffer from “reduced focus” or have “concentration deficits.”</p><p>Whether we are simultaneously cooking dinner and sending emails while</p><p>holding a baby or driving and eating breakfast while mentally organizing</p><p>the day’s schedule, the circus act of being a mom forces us to do more than</p><p>one thing at a time. As if that weren’t enough, we do so with a frequency</p><p>and a mastery that none of the standardized cognitive tests would ever</p><p>manage to measure. So please take heart, these shifts are in service to a</p><p>bigger picture, not ones that leave you wanting down the road.</p><p>Nonetheless, as another example of “no pain, no gain,” pregnancy and</p><p>postpartum are often accompanied by another challenge: mood changes. As</p><p>many as 70 to 80 percent of all new moms experience some depressive</p><p>symptoms within the first weeks to months after delivery. Symptoms</p><p>commonly include mood swings, crying spells, anxiety, and difficulty</p><p>sleeping. Interestingly, these mood swings can be similar to those of PMS—</p><p>and even related to it, as women suffering from PMS before pregnancy are</p><p>more likely to experience altered mood and depression during pregnancy.</p><p>And women who experience mood swings during pregnancy are more</p><p>likely to experience them again during menopause. This connection further</p><p>reveals the underlying thread of hormonal continuity that spans a woman’s</p><p>life.</p><p>About one in every eight new moms will experience something more</p><p>severe than the baby blues, struggling with postpartum depression.</p><p>Postpartum depression is a medical condition characterized by major</p><p>depressive episodes, deep sadness, sometimes crippling anxiety, and a loss</p><p>of self-worth that can last several weeks or more. In the United States alone,</p><p>half a million women suffer from this disorder every year. Sadly,</p><p>postpartum depression has long carried a social stigma. Society has deemed</p><p>but a single reaction acceptable in the face of motherhood, and that is joy.</p><p>Any lack of joy has been met with radical disapproval. It is also expected</p><p>that moms should show up equipped and proficient at their roles on day</p><p>one. This messaging is not only unrealistic but misleading, putting undue</p><p>pressure on the very person already carrying incomparable responsibilities.</p><p>Historically, mothers suffering from postpartum depression were called</p><p>madwomen and even thought to be cursed by witches—or to be witches</p><p>themselves. Quite remarkably, it wasn’t until 1994 that the psychiatric</p><p>community finally recognized postpartum depression as an actual medical</p><p>condition. Three decades later, it has become a household term, and</p><p>treatments are in place. However, many still don’t believe this condition is</p><p>real, filing it under “women’s imaginary problems.” To be clear,</p><p>experiencing depression, moodiness, or anxiety after giving birth isn’t in</p><p>any way, shape, or form reflective of a character flaw or weakness. Mood</p><p>changes are one of the many natural signs that your hormones and your</p><p>brain are undergoing a transition.</p><p>Changes in biology notwithstanding, having a baby is as lofty a pursuit</p><p>as they come—a quest that takes enormous strength of character to</p><p>entertain, let alone bear up under and see through. Motherhood is easy and</p><p>hard, beautiful and terrifying, and every woman’s experience is sacred and</p><p>important. In developing our children’s brains and behaviors, we teach them</p><p>the first lessons of love and seed their consciences. As society urges us to</p><p>seek worth apart from and in addition to this calling, I hope mothers</p><p>everywhere are aware of the worth of what they do and how far-reaching</p><p>their touch is.</p><p>A TALE OF VULNERABILITY AND RESILIENCE</p><p>How does all this relate to perimenopause? Because when it comes to</p><p>women’s brains and the Three P’s, every stage is marked by both</p><p>vulnerability and resilience. Puberty, for one, is often remarked upon with</p><p>an eye roll and a cringe. But while there is no question that this stage of life</p><p>comes with its own challenges, we now know that the teen brain serves a</p><p>higher purpose. The same brain</p><p>changes that trigger mood swings and fiery</p><p>emotions at the same time unlock intellectual and social maturation, helping</p><p>teens learn how to manage the intensity of life, a precursor to navigating the</p><p>rather weighty task of growing up and handling all that is ahead of them.</p><p>Pregnancy and postpartum are also stamped with the marks of</p><p>vulnerability and resilience. Yet again, the mommy brain isn’t just a state of</p><p>distraction and weepiness, but rather an indication that our brain is</p><p>developing vital new strengths and exceptional abilities. The changes our</p><p>brains undergo serve a fundamental evolutionary purpose, preparing a</p><p>woman for motherhood and, in doing so, supporting the survival of the</p><p>entire species.</p><p>There are pros and cons—both are part of being born with ovaries and</p><p>with a brain deeply connected to them. Keep this info handy because it will</p><p>be a recurring theme as we explore the last of the Three P’s.</p><p>7</p><p>The Upside of Menopause</p><p>A SHIFT IN PERSPECTIVE</p><p>As we’ve come to understand, our brains pass through a sequence of</p><p>hormonal transitions throughout our lives, first with puberty and then with</p><p>pregnancy, only to end in perimenopause. However, while a tsunami of</p><p>hormonal power accompanies both puberty and pregnancy, when fertility</p><p>recedes, many associate it with an ebbing tide instead—the beginning of the</p><p>end. In both culture and medicine, menopause is stigmatized as a flat-out</p><p>unfortunate event with little, if anything, positive to say about it. But this</p><p>reveals only one side of the coin. Upon further examination, menopause is</p><p>quite nuanced and much more individualized than sitcom stereotypes or</p><p>medicalized portrayals would have us believe. Whether we’re talking about</p><p>information passed down from mother to daughter or directly from doctor</p><p>to medical student to patient, the message has been flawed and sorely</p><p>lacking.</p><p>One of the most obvious pitfalls is that until recently, neither culture nor</p><p>science has bothered to perform a reality check on menopause. While they</p><p>have harped on the downsides, the upsides have remained ignored. What’s</p><p>missing from the conversation, therefore, is an accurate understanding of</p><p>how menopause fits into the larger picture of a woman’s life. This</p><p>understanding can be gained only by seeing menopause through the eyes of</p><p>the women living it, in league with the latest scientific data. In exploring</p><p>this life event without prejudice and free of preconceived notions, we</p><p>discover that perimenopause is just one more stop along the ride, not</p><p>dissimilar from puberty and pregnancy.</p><p>CONNECTING THE DOTS</p><p>Peering inside the brain, we see that the hormonal changes accompanying</p><p>perimenopause trigger brain symptoms not too different from those of</p><p>puberty and pregnancy. Changes in temperature, mood, sleep, libido, and</p><p>cognitive performance are very common during all Three P’s. As you can</p><p>see from table 4, the similarities are striking. After all, they involve the</p><p>same system, the neuroendocrine system, that gets activated and deactivated</p><p>at different stages of our reproductive lives.</p><p>TABLE 4. Similarities Between the Three P’s</p><p>PUBERTY PREGNANCY PERIMENOPAUSE</p><p>Changes in body temperature x x x</p><p>Changes in mood x x x</p><p>Changes in sleep patterns x x x</p><p>Changes in libido x x x</p><p>Changes in memory and attention x x x</p><p>Changes in brain gray matter x x x</p><p>Changes in brain energy x x x</p><p>Changes in brain connectivity x x x</p><p>Let’s talk about changes in body temperature, for example. Puberty may</p><p>not be associated with hot flashes as we know them, but it sure comes with</p><p>sweating—many times, lots of sweating—as the body’s sweat glands</p><p>become much more active at this stage. Additionally, for girls, body</p><p>temperature changes slightly with every menstrual cycle, peaking with</p><p>ovulation and falling with menstruation. During pregnancy, those same</p><p>mechanisms can once again prompt an increase in body temperature</p><p>(there’s a bun in the oven, after all), which can sometimes morph into</p><p>something else entirely: hot flashes. Although seldom cited, hot flashes are</p><p>another symptom pregnancy and perimenopause have in common, with</p><p>more than a third of all pregnant women sweating them out, too!</p><p>How about brain fog? It’s a well-known fact that most teenagers have</p><p>their heads in the clouds, with difficulty concentrating or remembering</p><p>information. For girls, this can intensify during the late phase of the</p><p>menstrual cycle. As we discussed, brain fog is quite common during</p><p>pregnancy and postpartum, too.</p><p>What instead distinctly differs is how we perceive the first two P’s versus</p><p>the last. Puberty and pregnancy are no picnic either, but here we tend to</p><p>focus on the positives. During our children’s teen years, we fill photo</p><p>albums with snapshots of them at the prom, on the athletic field, and in the</p><p>classroom, celebrating a parade of coming-of-age milestones. We do the</p><p>same with pregnancy, showering mothers-to-be with gifts and parties as we</p><p>shop and prepare in anticipation of the baby’s arrival. When hit with the</p><p>tough stuff of these transitions, we stay upbeat. Whether it’s pimples and</p><p>periods or swollen ankles and morning sickness, we say to ourselves, This,</p><p>too, shall pass, and tend to react with sympathy and support. If a teenage</p><p>girl is irritable and has trouble focusing, we chalk it up to adolescence and</p><p>give her time and space to muddle through. Similarly, if a pregnant woman</p><p>is crying for no clear reason, we think, It’s her hormones, and give her a</p><p>hug. In both cases, we err on the side of optimism and encouragement.</p><p>While this approach can inadvertently result in some serious symptoms not</p><p>being addressed, the overall intention is one of allowance and reassurance.</p><p>But when those same behaviors crop up in a perimenopausal or</p><p>postmenopausal woman, they are most often met with the opposite reaction:</p><p>an absence of support, visible annoyance, or even disdain. Or at times,</p><p>denial. Conversations about menopause lack, among so many other things,</p><p>a nuanced language to help doctors gauge the problem in the first place. For</p><p>instance, it is understood (and accepted) that some women menstruate every</p><p>month without much discomfort, while others have a hard time, or PMS, or</p><p>in more severe cases, premenstrual dysphoric disorder. Likewise, some</p><p>women sail blissfully into motherhood, while others experience severe</p><p>symptoms of postpartum depression, anxiety, and cognitive fatigue. The</p><p>fact that we have words to describe this range of symptom severity not only</p><p>enables accurate diagnosis and treatment but legitimizes their validity.</p><p>There is no such distinction for women who experience severe symptoms of</p><p>menopause. The compassion factor isn’t there, either. During</p><p>perimenopause in particular, many women are met with a sour “You still</p><p>have your period, so grin and bear it.”</p><p>It is no wonder menopause is felt as a moment of doom and gloom when</p><p>those experiencing it are disregarded rather than embraced, the event itself</p><p>interpreted as anything from sheer exaggeration on the one hand to a</p><p>disease on the other. But the idea that menopause might put women at a</p><p>disadvantage is one that history and culture—not biology—have inflicted</p><p>upon us. In fact, from a biological perspective, some of the same positives</p><p>that apply to puberty and pregnancy may well apply to perimenopause, too.</p><p>If you’ve been following how the prior two P’s work, the fact that the</p><p>brain changes during menopause (just like it does during those other</p><p>milestone periods) won’t be as surprising or alarming. So here’s the million-</p><p>dollar question: To what degree does menopause also deliver a customized</p><p>update to your brain’s operating system?</p><p>It is plausible that as the brain approaches menopause, it gets another</p><p>chance to go leaner and meaner, discarding information and skills it no</p><p>longer needs while growing new ones. For starters, some of the brain-ovary</p><p>connections necessary to make babies are no longer needed, so arrivederci</p><p>to that. But also all the neurologically expensive skills we reviewed in the</p><p>last chapter—decoding baby talk, subduing temper tantrums,</p><p>and high-level</p><p>multitasking—are not as relevant once your birdie has flown the coop. They</p><p>are still helpful, but not urgent. It only makes sense, then, that the brain</p><p>would eventually start pruning away those expired connections—and what</p><p>better biological clue to do so than menopause. Again, many believe that, as</p><p>this latest and greatest brain update unfolds, that’s when hot flashes, brain</p><p>fog, and other bothersome symptoms kick in. Once the update is complete,</p><p>the symptoms start dissipating (which may take longer than the other two</p><p>P’s because now we are... well, older).</p><p>All this information is helpful to place menopause under a much broader</p><p>lens. But where are the bonuses? Could it be that the menopausal brain</p><p>morph might better equip us for our later years? Could menopause come</p><p>with its own ingenuity, proving instrumental in preparing women for a new</p><p>role in life as in society? Despite society having turned a blind eye toward</p><p>any menopausal perks, there is increasing evidence that this profound</p><p>hormonal event also bestows new meaning and purpose on women.</p><p>HAPPINESS IS NOT A MYTH AFTER ALL</p><p>Any major life transition can be a chance at reawakening, even if the road is</p><p>rough. While the general mindset in the Western world is that menopause</p><p>takes things away from us, the untold story is that it’s also busy endowing</p><p>us with new gifts. Consider, for example, something everyone wants but</p><p>few master: happiness.</p><p>You’ve heard that right. One of the more surprising things I’ve learned is</p><p>that postmenopausal women are generally happier than younger ones—and</p><p>generally happier than they themselves were before menopause. According</p><p>to several studies, some of the most notable and overlooked upsides of</p><p>menopause revolve around better mental health and greater contentment</p><p>with life. In the Australian Women’s Healthy Ageing Project, for example,</p><p>postmenopausal women reported improved mood, more patience, less</p><p>tension, and feeling less withdrawn as they entered their sixties and</p><p>seventies. Similar results hail from studies conducted in Denmark, where</p><p>postmenopausal women shared experiencing a stronger sense of well-being</p><p>after menopause, with 62 percent stating that they felt, indeed, happy and</p><p>satisfied. About half of these women also stated that they were as happy as</p><p>they’d ever been, even at a younger age. Likewise, the Jubilee Women</p><p>Study found that 65 percent of British postmenopausal women were happier</p><p>than they were before menopause, feeling more independent and enjoying</p><p>better relationships with partners and friends. If nothing else, these insights</p><p>debunk the stereotype of the unhappy and dissatisfied postmenopausal</p><p>woman.</p><p>Contrary to popular assumptions, preconceived notions, and even</p><p>marketing, the evidence points to a fairly nuanced relationship between</p><p>menopause and life satisfaction. Take a look at figure 8. The thicker line</p><p>marks the effect of menopause on women’s life satisfaction over time (with</p><p>vertical lines marking differences among different women), starting five</p><p>years before menopause through ten years after menopause. Time 0 marks</p><p>the point when menopause took place.</p><p>Figure 8. Menopause vs. Life Satisfaction</p><p>The most important data everyone needs to see:</p><p>Perimenopause: Most women indeed grow unhappy in the three</p><p>years or so building up to menopause.</p><p>After menopause: Life satisfaction tends to remain low for two to</p><p>three years after the final menstrual period, but then increases well</p><p>past baseline and remains steadily higher over time.</p><p>The bottom line: Menopause tends to affect life satisfaction mainly in the</p><p>short run. Most women adapt to the change, usually within a couple of</p><p>years into their postmenopausal life. After this point, menopause no longer</p><p>seems to have a negative impact on happiness and perhaps may even lead to</p><p>more contentment. While this awaits confirmation, it is consistent with</p><p>more general observations that happiness and life satisfaction tend to follow</p><p>a U-shaped curve. Multiple studies indicate that contentment is relatively</p><p>high in young adulthood but slowly drops and hits a low point at about age</p><p>fifty (the average age of menopause). Then it steadily climbs to new heights</p><p>later in life. Believe it or not, by the time we’re in our sixties, it’s</p><p>statistically probable that we’ll never have been happier. Of course,</p><p>everyone’s different, and an individual’s personal experience may stray</p><p>from the norm for many reasons. Still, the U-shaped curve reinforces the</p><p>notion that the midlife menopausal slump is temporary.</p><p>“Menostart”: A Second Adulthood</p><p>Now, does menopause itself bring contentment, or are women happier after</p><p>menopause because the symptoms are gone?</p><p>It just so happens that menopause can leverage a positive impact on your</p><p>life in addition to its apparent hurdles. For one thing, not all its physical</p><p>changes are negative. According to national surveys, the increase in mood</p><p>and optimism reported by many postmenopausal women is often related to</p><p>being finished with periods, PMS, and concerns about pregnancy. For many</p><p>women, the end of their period is a cause for celebration in and of itself. It</p><p>signifies the grand finale to certain elements of inconvenience: no more</p><p>tampons, no more pads, no more cramps—after decades of them.</p><p>Menopause also shrinks uterine fibroids, a major cause of heavy bleeding,</p><p>and it kicks out PMS, which for 85 percent of women means the end of a</p><p>range of complex symptoms from breast tenderness and irritability to</p><p>debilitating migraines. This latitude is a big plus for more women than you</p><p>may imagine. And as yet another positive note, enjoying sex without</p><p>thinking about possible unanticipated outcomes is frequently cited as one of</p><p>the utmost benefits of menopause.</p><p>But also, plenty of women have positive attitudes toward menopause—</p><p>not only once the symptoms subside but even when they are in the thick of</p><p>it. At some point in my research, I came across the term menostart as an</p><p>alternative to menopause. This word seems apt for the many women who</p><p>experience this life transition as a turning point, after which their interests,</p><p>priorities, and attitudes shift in a positive way. A second adulthood, if you</p><p>will, or a renaissance of sorts is entirely possible. American anthropologist</p><p>Margaret Mead called it “menopausal zest”—the rush of physical and</p><p>psychological energy some women experience after menopause. You may</p><p>not have the frenetic energy of a teenager, but you may find yourself</p><p>pondering new beginnings: a new career, new relationships and interests,</p><p>new places to live or travel, renewed health and self-care practices, and an</p><p>all-around refresh as to how you channel your time and energy. Many</p><p>women are also only too happy to have more me-time as they wind down</p><p>from full-time work and family responsibilities. While this is not</p><p>necessarily thanks to menopause itself, the prospect of personal growth and</p><p>the freedom to concentrate on their own interests is a luxury they are finally</p><p>free to accept. As Oprah Winfrey once said: “So many women I’ve talked</p><p>to see menopause as a blessing. I’ve discovered that this is your moment to</p><p>reinvent yourself after years of focusing on the needs of everyone else.” In</p><p>the grand scheme of things, if that isn’t a plus, I don’t know what is.</p><p>Emotional Mastery</p><p>Hand in hand with contentment comes another much-coveted attribute: self-</p><p>transcendence. Or, as some may put it, “giving fewer f***s.” This theme</p><p>repeatedly surfaces in postmenopausal women’s accounts of their</p><p>experience of this milestone. They describe the ability to draw a line</p><p>regarding others’ needs, finally able to pay attention to their own. Once</p><p>they have managed menopause, whether it’s been a stroll in the park or a</p><p>walk through fire, many women tend to emerge more confident and less</p><p>constrained, with renewed vigor and a take-no-baloney attitude.</p><p>During this period, some things take a hike, like the weight of pressures</p><p>felt by youth, a preoccupation with various social games, or any inclination</p><p>to wear Daisy Dukes. At the same time,</p><p>new perspectives arise—a</p><p>refreshed sense of self and an awareness of new opportunities and choices.</p><p>This empowerment is due partly to biological triggers and partly to the</p><p>timing of menopause. With fifty-plus years of life experience under their</p><p>belt, many postmenopausal women have developed a nice set of life skills,</p><p>giving them a greater confidence they can handle whatever comes their</p><p>way. By then, a woman has experienced her own array of challenges, losses,</p><p>illnesses, and disappointments, and has better discerned who she is, what</p><p>she wants, and what she prizes. She realizes she is stronger and more</p><p>capable than she imagined, and is much less likely to spend time brooding</p><p>over bad experiences, mistakes, and blunders.</p><p>Notably, many postmenopausal women also report that emotions like</p><p>sadness and anger don’t hold quite the same charge as they once did, while</p><p>the capacity to sustain joy, wonder, and gratitude often increases. There is a</p><p>neurological reason for these shifts. Among other things, all the</p><p>rearrangements in the menopausal brain may result in yet another upgrade</p><p>to some networks involved in the theory of mind. Only this time, the</p><p>transition brings forth better emotional control. If you recall from the</p><p>previous chapters, how we respond to emotionally charged situations</p><p>depends partly on how we’re wired in our brains. Connections related to the</p><p>emotion-processing amygdala versus the impulse-controlling prefrontal</p><p>cortex can influence our approach. Puberty asks us to lean into the</p><p>prefrontal cortex’s rationale, whereas pregnancy attunes us to our instincts</p><p>(while striking a balance between our emotions and our head). Now it’s</p><p>menopause’s turn. This time around, we are about to fine-tune the</p><p>emotional amygdala in a highly selective and precise way: it becomes less</p><p>reactive to negative emotional stimulation! If you present postmenopausal</p><p>and premenopausal women with negative and positive imagery and</p><p>compare their brain activity, you’ll notice that the postmenopausal</p><p>amygdala is less responsive to emotionally unpleasant information. At the</p><p>same time, postmenopausal women tend to activate their rational prefrontal</p><p>cortex more than premenopausal women do. This result reinforces the idea</p><p>that, after menopause, we have overall better control of our emotions,</p><p>particularly our reactions to sad or upsetting ones. Isn’t that a superpower in</p><p>its own right?</p><p>Greater Empathy</p><p>This fresh research brings to light new notions of resilience, well-being, and</p><p>emotional flexibility with regard to menopause. For instance, menopause</p><p>has been linked to a boost in another skill related to the theory of mind:</p><p>empathy. As it turns out, postmenopausal women are the ultimate empaths.</p><p>According to a study of over 75,000 adults, women in their fifties show</p><p>greater empathy than their male counterparts, being more likely not only to</p><p>react emotionally to the experiences of others but also to try to understand</p><p>how things looked from the other person’s perspective.</p><p>Other studies found that a specific type of empathy called empathic</p><p>concern or sympathy continues to increase as women age. This may be</p><p>particularly the case when it comes to caring for... grandchildren. As we</p><p>pointed out in chapter 6, scientists believe that the brain changes occurring</p><p>with pregnancy may be advantageous later in life, when older women</p><p>assume the role of caregivers. In a recent study, researchers tested this</p><p>theory by using brain scans to explore grandmothers’ emotional reactions to</p><p>others. To do so, they monitored brain activity across a group of</p><p>grandmothers as they perused photos of their children and grandchildren—</p><p>versus images of children they didn’t know. (If you recall from the last</p><p>chapter, this study is similar to the one researching pregnancy.) The results</p><p>turned up interesting information about intergenerational bonding. When</p><p>the grandmothers looked at pictures of their grandkids, the scientists</p><p>witnessed brain activity in areas associated with emotional empathy—</p><p>which is the ability to feel another person’s feelings or to put oneself in</p><p>another’s shoes. But when the grandmothers looked at pictures of their</p><p>children instead of grandchildren, their brain activity relocated to areas of</p><p>the brain linked with another form of empathy, called cognitive empathy,</p><p>instead. Cognitive empathy is more about understanding another’s feelings</p><p>on an intellectual level, focusing not only on what someone is feeling but</p><p>on why. Interestingly, the more a grandmother was involved in the everyday</p><p>caring for her grandchildren, the more activation she showed in both the</p><p>emotional and the cognitive empathy zones.</p><p>You may have experienced this yourself, in a real-life way. If you have</p><p>children, have you ever observed that your mother has a different</p><p>relationship with them than she had with you when you were their age?</p><p>Perhaps she appears more relaxed, easygoing, and demonstrative? The</p><p>findings I’m referring to help explain why. As a mother, you are tasked with</p><p>molding and guiding your children, often with achievement-oriented tasks</p><p>and accomplishments in mind. Generally speaking, mothers do this under</p><p>the substantial weight of caregiving responsibility and demands. This</p><p>responsibility is no longer the case when you are a grandmother, though, as</p><p>it’s now your adult child’s job to carry that burden. While they are</p><p>sometimes blamed for spoiling their little ones, perhaps grandmothers are</p><p>finally at liberty to respond with more yesses than noes—along with an</p><p>extra helping of dessert! This broader, wiser view is built right into the</p><p>brain of a grandmother, acting as a backup for her child while prioritizing</p><p>the preciousness of unrestricted love.</p><p>Personally, what I like most about these findings is the view of women’s</p><p>responsibilities changing through our lifespan, whether one has biological</p><p>children and grandchildren or doesn’t. I am moved by how many of us</p><p>fulfill multiple roles, often beyond blood ties—and how our brains appear</p><p>to adjust and adapt to the current circumstances, at all ages and in all walks</p><p>of life. In this spirit, in the next chapter we will spotlight how women’s</p><p>brains continue to kaleidoscope into fresh talents and strengths for a</p><p>lifetime of use, as we delve into the evolutionary significance of</p><p>menopause.</p><p>8</p><p>The Why of Menopause</p><p>MENOPAUSE: BY ACCIDENT OR DESIGN?</p><p>While the biology of menopause—the when and the what—are relatively</p><p>well understood, the why has still not come clear. For anyone with ovaries,</p><p>menopause is a fact of life, one we tend to either ignore or take for granted.</p><p>In reality, menopause is a long-standing biological riddle, one that scientists</p><p>haven’t managed to explain fully. In fact, menopause appears to be at odds</p><p>with evolution itself. From an evolutionary perspective, the whole point of</p><p>life is to survive, procreate, and pass on our genes to the next generation.</p><p>Menopause puts a stop to the transmission of a woman’s genes, evolution’s</p><p>sole argument for female longevity. As postulated by Darwin, “If the main</p><p>purpose of females is to propagate the species, then going through</p><p>menopause many years before dying should be selected against, unless</p><p>there are distinct advantages to it.”</p><p>Well, we are not dead, are we? It is undeniable that there is something</p><p>unique about human menopause. If we look out across the entire animal</p><p>kingdom, most females do in fact die soon after they lose their ability to</p><p>procreate. Even chimpanzees, our closest mammalian relatives, do not</p><p>typically live past menopause. The few who make it are zoo captives who</p><p>survive just a few years more. The only animal species known to outlive</p><p>their fertility are certain whales, some Asian elephants, possibly some</p><p>giraffes, and one insect, the Japanese aphid.</p><p>Anthropologists, evolutionary biologists, and geneticists have all been</p><p>spinning their wheels over this. Until fairly recently, menopause was</p><p>written off as the unnatural result of women’s increased life expectancy,</p><p>treated as the unfortunate upshot of our living well beyond what nature</p><p>intended.</p><p>One long-held view, the evolutionary mismatch hypothesis, insists</p><p>that there is no benefit to menopause. They posit that modern medicine</p><p>keeping us alive longer has unwittingly duped our genetic code, and that</p><p>menopause is a fluke.</p><p>Not so fast. There is also reason to believe the exact opposite might be</p><p>true. What if evolution isn’t as misogynistic as those who conceived of it?</p><p>Perhaps nature doesn’t measure a woman’s worth based on her ability to</p><p>crank out as many children as humanly possible. If you start thinking</p><p>outside the box, as one so often must do with women’s health, an alternative</p><p>hypothesis starts taking shape. What if evolutionary forces are still behind</p><p>menopause, but this time, they favor women for once?</p><p>EVOLUTION’S SECRET HEROINES: GRANDMOTHERS</p><p>The view of menopause as an evolutionary adaptation instead of an</p><p>evolutionary oversight was developed in 1957 by late ecologist George C.</p><p>Williams. His idea didn’t gain traction until much later, thanks to field data</p><p>collected by Dr. Kristen Hawkes, a professor of anthropology at the</p><p>University of Utah. Dr.Hawkes pulled a team together to extensively study</p><p>the Hadza, a group of modern hunter-gatherers who have lived in northern</p><p>Tanzania for thousands of years. Observing communities like the Hadza</p><p>gave her a time-machine-like peek into how our early ancestors might have</p><p>lived. Her research, however, didn’t start with menopause, but with food.</p><p>A seed of an idea began to develop as Dr.Hawkes watched women of the</p><p>tribe collecting vegetables. Often with younger children in tow, women</p><p>young and old went on daily excursions to pick berries, wild fruit, and</p><p>nutritious tubers. Suddenly it became clear that these female foragers were</p><p>providing the majority of calories and sustenance to their families and tribe</p><p>mates. In fact, while the men went out hunting daily, they returned with a</p><p>substantial haul only about 3 percent of the time. So dad wasn’t bringing</p><p>home the bacon, after all—mom was. But the researchers’ work was further</p><p>enlightened by a shift observed as the younger women went on to have</p><p>children. A pattern quickly emerged that revealed coalitions of</p><p>grandmothers covering all gathering and feeding responsibilities. Since</p><p>then, many studies of modern hunter-gatherers have shown that grandma is</p><p>doing much of the work the world over. Although these women are no</p><p>longer reproductive, they remain markedly productive in providing food</p><p>and carrying out the chores that keep a village running. By doing so, the</p><p>grandmothers were at the heart of keeping their people safe not only by</p><p>ensuring their food supply was secured and abundant, but also by</p><p>maximizing reproduction potential and the passing on of genes so precious</p><p>to human evolution. How so?</p><p>The idea is that prehistoric mothers faced a conflict between foraging for</p><p>food for themselves and their families and caring for their new infants.</p><p>However, struggling with this sacrifice was no longer necessary once</p><p>grandmothers stepped in to save the day. As the elder women took over the</p><p>care of their grandchildren, they also allowed their daughters to produce</p><p>additional offspring, doubling down on the odds of survival of the species.</p><p>Evidence of just how much impact grandmothers’ contributions had on</p><p>childhood survival led Dr. Hawkes to reevaluate what was known about</p><p>menopause and human evolution. Her aptly named grandmother hypothesis</p><p>proposes that ceasing reproduction around age fifty, and living to tell the</p><p>tale, allowed older women to devote care and resources to their children’s</p><p>children rather than birthing and nurturing new ones themselves. Since the</p><p>process of childbirth becomes riskier with age, this seems like it might be</p><p>nature’s way of leveraging a savvy bet. After all, grandmothers still ensured</p><p>the survival of their genes, genes that were just two generations down the</p><p>family tree. Notably, if it weren’t for menopause, such contributions would</p><p>be impossible. Suddenly this so-called anomaly could be seen as nothing</p><p>less than the epitome of nature’s wisdom.</p><p>Is Menopause the Key to Human Longevity?</p><p>The potential of nature taking menopause’s side doesn’t end there. Other</p><p>evidence points to the idea that menopause may even be why humans</p><p>evolved to live as long as we do today. In fact, the prehistorical</p><p>grandmothers in question weren’t just any grandmothers. We are talking</p><p>about “naturally selected” grandmothers. Natural selection refers to the</p><p>survival of the fittest. These women had the strength to survive childbirth</p><p>multiple times and the genetic makeup to live past menopause, which, the</p><p>theory goes, was bestowed onto their children and grandchildren, carrying</p><p>grandma’s longevity genes well into the future. Over time, this survival</p><p>boost could have provoked an evolutionary shift, favoring and selecting for</p><p>women who survived long past menopause. Under this hypothesis,</p><p>postmenopausal life would become more and more common until, over</p><p>time, every female Homo sapiens carried DNA with a cap on fertility and</p><p>increased longevity in its place.</p><p>The theory is plausible, but is it scientifically sound?</p><p>Many believe so. For instance, research on killer whales, who also live</p><p>past menopause, supports the grandmother hypothesis. Killer whale</p><p>societies are matriarchal, and sons and daughters live out their lifetimes</p><p>with their mothers rather than with their fathers. In addition, once mothers</p><p>become grandmothers, they stick close by to help raise their grandchildren.</p><p>In their world, it is indeed advantageous for mothers to lose their fertility</p><p>after a certain age, eliminating any reproductive competition with their</p><p>daughters and daughters-in-law. Match that with recent studies indicating</p><p>how grandmother whales increase their aquatic grandkids’ survival in other</p><p>ways—for example, by sourcing food—and we begin to establish a pattern.</p><p>Given that a similar societal pattern is indicated in ancient hunter-gatherer</p><p>societies, perhaps menopause was nature’s way of avoiding a similar</p><p>mother-daughter conflict in our species, too. As we’re about to prove,</p><p>grandma’s tendency to keep her kids’ bellies full has long been part of</p><p>human history—from as far back as our Paleolithic communities to our</p><p>current-day holiday tables.</p><p>Grandma Lays the Groundwork</p><p>Baby chimpanzees, bonobos, orangutans, and gorillas are all cared for</p><p>exclusively by their mothers. These primate moms are extremely protective</p><p>of their babies, sometimes not letting other apes touch them for months</p><p>after birth. In contrast, it’s likely that grandmothers were present for their</p><p>prehistoric grandchildren from the moment of birth. Scientists believe that it</p><p>was common for children to be fed and raised by their grandmothers, so this</p><p>bond likely fostered our species’ deep social orientation. As humans, we</p><p>distinguish ourselves from other animals by being able to sense the thoughts</p><p>and intentions of others (the theory of mind) and to care about them</p><p>(empathy). Both skills women in general, and postmenopausal women in</p><p>particular, excel at.</p><p>Our ancestral grandmothers may have had a central role in building these</p><p>senses. Think of it this way. If successful interactions with a child’s</p><p>grandmother made the difference between getting a full meal or going</p><p>hungry, successful connection and communication between the two might</p><p>also have bred critical social skills in the grandchildren. We still see</p><p>modernized signs of this today. Images of grandma walking in the door are</p><p>often punctuated by her grandchild’s greeting her with outstretched arms</p><p>and broad smiles, and the two embracing and exchanging a trinket or a</p><p>sweet. At the beginning of our long history, this primal interaction may</p><p>have begun with our bonding over tubers and berries. Whatever the case,</p><p>caring for and feeding our young plays a critical role in promoting</p><p>cooperation and social orientation in ways distinctive to our species. Our</p><p>ability to figure things out by “putting our heads together” ultimately sets</p><p>our species apart from all other animals. According to the latest research, a</p><p>new picture</p><p>of human society emerges, with fathers out hunting and</p><p>mothers busy giving birth and nursing—while grandmothers kept the</p><p>communal cogs oiled and rolling. It seems possible, if not probable, that</p><p>humanity’s evolution may have been built upon such a pattern, resulting in</p><p>the unique timing of menopause and female longevity we see today.</p><p>WOMEN OF ALL AGES</p><p>Although everyone agrees grandmothers can provide welcome childcare</p><p>support and resources for their children raising new babies, the notion that</p><p>grandmothers were also integral in bestowing our longevity has been</p><p>challenged. While scientists work it out, it’s heartwarming to think of older</p><p>women as evolutionary heroines, especially in light of the alternative</p><p>narrative. The commonly held viewpoint to date is that postmenopausal</p><p>women are a sort of collateral damage resulting from evolution’s failure to</p><p>sustain fertility throughout a woman’s entire life. Are we satisfied with this</p><p>explanation?</p><p>Once again, it is helpful to look at menopause through a neuroscientist’s</p><p>lens. Humans evolved under different evolutionary pressures than other</p><p>animal species, pushing the development of distinctive cognitive and social</p><p>skills. As we’ve reviewed over these past chapters, at various crossroads in</p><p>a woman’s life, brain-hormone events promote social and cognitive</p><p>upgrades or adaptive advantages. Whether preparing us for adulthood after</p><p>puberty, promoting nurturing abilities after pregnancy, or honing us for</p><p>unique societal roles after menopause, our neuroendocrine networks seem</p><p>to have a plan in mind.</p><p>The grandmother hypothesis may be controversial, but the importance of</p><p>grandmothers in the lives of many families is not, and neither is the</p><p>influence and benefaction of elder women in countless societies the world</p><p>over. Grandmother by blood or choice, those that care for us in this way are</p><p>of inestimable value and have been for millennia. Those who have known</p><p>the blessing of one understand this implicitly. Since women today live far</p><p>longer than ever, the time has come to roll up our sleeves and figure out</p><p>how we can protect and invigorate our minds to ensure this legacy. While</p><p>hormones may ebb, we shall not.</p><p>PA RT 3</p><p>HORMONAL AND</p><p>NONHORMONAL THERAPIES</p><p>9</p><p>Estrogen Therapy for Menopause</p><p>THE ESTROGEN DILEMMA</p><p>What is it about hormone therapy that makes it so confusing? Is hormone</p><p>replacement as dangerous as some people say it is—or is it the cure-all that</p><p>its superfans insist? No matter how straightforward you wish the answer to</p><p>this question was, it remains stubbornly layered with so many ifs, ands, and</p><p>buts.</p><p>Unfortunately, this wild-goose chase is par for the course when we are</p><p>attempting to make heads or tails of hormone replacement therapy, or HRT.</p><p>[*] By the time a woman begins navigating menopause, HRT has</p><p>undoubtedly crossed her radar. The idea behind this therapy is to replace</p><p>those hormones that the ovaries cease to produce, chiefly estrogen (or</p><p>estrogen and progesterone), with the same hormones contained in pills,</p><p>patches, and creams, among other options. While this is logical in principle,</p><p>weighing the benefits and risks has made this choice challenging for</p><p>providers and patients alike. Many women are frightened of hormones due</p><p>to warnings about increased risks of cancer, heart disease, and stroke.</p><p>Others are discouraged from going on HRT by their own doctors without</p><p>further discussion. Others remain unclear about whether HRT can</p><p>effectively treat menopausal symptoms in the first place, scouring the</p><p>internet and discussing options ad nauseam with friends. Before long,</p><p>however, confusion reigns and you find yourself on Amazon, perusing</p><p>concoctions from rare jungle herbs that are supposed to cool your hot</p><p>flashes and stoke your libido at the same time! We can do better than this.</p><p>This chapter aims to take some of the mystery out of the debate by</p><p>reviewing HRT’s actual bottom-line risks and benefits. We will first</p><p>examine how HRT got such a bad reputation, and then explore the recent</p><p>shift that has sparked a renaissance in the use of hormone therapy for</p><p>treatment of menopausal symptoms, with a particular focus on the brain</p><p>symptoms we’ve reviewed so far.</p><p>THE GOLDEN AGE OF HRT</p><p>In the past, menopause treatment was a veritable house of horrors, from</p><p>opium to exorcism and institutionalization. Eventually scientists discovered</p><p>estrogen and some of its functions, leading to the widespread use of</p><p>estrogen replacement for menopause. In 1942, the U.S. Food and Drug</p><p>Administration approved the first hormone replacement therapy drug called</p><p>Premarin, marketed by Wyeth Pharmaceuticals (now owned by Pfizer). This</p><p>estrogen pill quickly became a national bestseller.</p><p>Despite its meteoric rise in the seventies, at this point HRT hit the first of</p><p>many speed bumps. It turned out that Premarin increased the risk of</p><p>endometrial cancer in the uterus. However, researchers found that reducing</p><p>the dose of estrogen and adding a progestin (a synthetic form of</p><p>progesterone) protected the uterus, leading to the release of a second pill</p><p>called Prempro, containing both estrogen and progesterone. The scare over,</p><p>HRT was hot again. By 1992, Premarin was the number one prescribed</p><p>drug in the United States, with sales exceeding $1 billion. Millions of</p><p>women jumped on the bandwagon, partly because Wyeth’s marketing</p><p>promoted hormone replacement as the ticket to a vibrant, sexy</p><p>postmenopausal life, and partly because most physicians were also on</p><p>board, suggesting it to patients without hesitation. Once women start losing</p><p>estrogen, they argued, taking replacement hormones could cure hot flashes,</p><p>protect against heart disease, keep bones strong, and improve one’s sex life</p><p>to boot—what more could a girl want? By this time, major professional</p><p>societies were also endorsing HRT as an effective first-line solution not</p><p>only for hot flashes but for the prevention of heart disease and osteoporosis.</p><p>After all, early scientific studies and lots of anecdotal evidence backed up</p><p>the claims: women on HRT reported having fewer hot flashes while also</p><p>experiencing less bone loss and a lower rate of heart disease than those</p><p>opting out. While HRT carried a risk of breast cancer that was worth</p><p>considering, women were advised not to worry too much about that, unless</p><p>a history of breast cancer was present. The choice seemed obvious: as soon</p><p>as menopause hit, it was time to go on hormones. So by the nineties,</p><p>hormone therapy wasn’t just about being “feminine forever.” Now it was</p><p>also touted as “healthy forever.”</p><p>The Fall from Grace</p><p>In 2002, a bombshell exploded in the medical establishment. The study at</p><p>the center of the commotion was called the Women’s Health Initiative</p><p>(WHI). It was a federally financed examination of HRT started in the early</p><p>nineties, extraordinary in both its scale and ambition: almost 160,000</p><p>postmenopausal women were enrolled in a multiyear comparison of</p><p>estrogen pills with or without progesterone versus placebos. The goal was</p><p>to provide conclusive evidence as to whether all this widescale prescribing</p><p>of HRT was indeed a sound idea, with a particular focus on preventing heart</p><p>disease. But on July 9, 2002, WHI investigators made the shocking</p><p>announcement that they were pulling the plug on the trial three years</p><p>earlier than planned.</p><p>As it turned out, HRT was “too dangerous” to the participants’ health to</p><p>proceed. The women on hormones had more heart trouble than their</p><p>placebo-taking counterparts, instead of less. Their risk for stroke was on the</p><p>rise, too, as was their risk for blood clots and breast cancer. Just as</p><p>surprisingly, even their risk of dementia had gone up. Somehow HRT was</p><p>doing precisely the opposite of what was intended and then some. The WHI</p><p>bulletins dominated medical news all summer and long into the autumn. So</p><p>dire were their broadscale warnings that millions of women stopped HRT</p><p>on the spot. Sales of estrogen pills plummeted. Drug development for</p><p>menopause came to a screeching halt. The news was out: HRT was now</p><p>considered deadly.</p><p>THE WHI REVISITED:</p><p>THE WRONG DRUGS, TESTED ON THE WRONG</p><p>POPULATION</p><p>Over twenty years have passed since the WHI kaboom. A ferocious</p><p>hormone debate has been roaring since, questioning both the study’s</p><p>validity and its findings. Now that the smoke has cleared, we find that the</p><p>fine (and not so fine) print on the subject matters a very great deal.</p><p>The Importance of Having (or Not Having) a Uterus</p><p>Let’s start with the basics. If you possess a uterus, then you will receive</p><p>both estrogen and a progestogen (a generic term including different types of</p><p>progestogenic preparations). (Just as a reminder, this is because estrogen</p><p>alone can increase the risk of uterine cancer, while progesterone lowers this</p><p>risk.) This two-hormone treatment is called estrogen-plus-progesterone</p><p>therapy, but also combination therapy, or opposed therapy. If you’ve had a</p><p>hysterectomy and no longer have a uterus, then you are not at risk for</p><p>uterine cancer and don’t usually need the progesterone. In this case, it is</p><p>standard practice to prescribe estrogen alone. This is called estrogen-only,</p><p>or unopposed, therapy.</p><p>The WHI study did include two clinical trials designed to reflect this</p><p>distinction. The first trial, which caused such a stir in 2002, was designed</p><p>for women with uteruses, who were prescribed Prempro, the estrogen-plus-</p><p>progesterone therapy. The progesterone used in this preparation is called a</p><p>“progestin,” which is a synthetic form of the hormone. The second trial</p><p>involved women who had undergone hysterectomies and were given</p><p>Premarin, the estrogen-only treatment. Each group was compared to a</p><p>placebo group of women who did not receive hormones. In the end, both</p><p>trials were shut down due to an increased risk of stroke and blood clots.</p><p>However, the risk of breast cancer was increased only for women taking the</p><p>estrogen-plus-progestin therapy. The estrogen-only treatment had precisely</p><p>the opposite effect, with a 22 percent reduced occurrence of breast cancer.</p><p>The media, however, zoomed in on the cancer scare of the first trial,</p><p>generating public panic around both types of HRT and leaving</p><p>apprehension in its wake present to this day. Fortunately, we now have a</p><p>more nuanced understanding of if and when this cancer risk exists, which</p><p>we’ll discuss ahead.</p><p>Oral, Transdermal, Bioidentical, Compounded... Oh, My!</p><p>Another fly in the WHI ointment was that different estrogen preparations</p><p>can have different effects. Currently, there are two main types:</p><p>Conjugated equine estrogens. The kind of estrogen used in the WHI</p><p>trials is called conjugated equine estrogen, or CEE. CEEs are a</p><p>concentrated formula manufactured from the urine of pregnant</p><p>horses, which typically contains more than ten different forms of</p><p>estrogen, mainly estrone, and smaller amounts of estradiol.</p><p>Estradiol. Today, estradiol itself is available, and is called</p><p>micronized estradiol. It typically comes from yam whose molecules</p><p>have been tweaked until they are atom-for-atom identical to our</p><p>ovary-produced estradiol. For this reason, it is also referred to as</p><p>bioidentical, or body-identical estrogen.</p><p>Synthetic replications of the equine preparations, called synthetic</p><p>conjugated estrogens (CE), are also available and so is synthetic estradiol</p><p>(ethinyl estradiol), which is often used in hormonal contraceptives.</p><p>These are the main types of estrogen at our disposal. Additionally, the</p><p>way estrogen is delivered and whether its effects are local or widespread</p><p>also matters. HRT is a systemic therapy, which means it is designed to</p><p>release hormones through the bloodstream to be absorbed throughout the</p><p>body, therefore having systemic (whole-body) effects. This occurs via two</p><p>main routes of delivery:</p><p>Oral route (by mouth). When the WHI was running its study,</p><p>estrogen (specifically, CEEs) was taken at high doses and always</p><p>orally, as pills. Oral estrogen metabolizes through the liver, possibly</p><p>creating additional complications before going about its business.</p><p>Scientists believe that the use of oral CEEs might have further</p><p>muddied the waters of the WHI studies, as some studies have found</p><p>that oral estradiol may be safer than oral CEEs.</p><p>Transdermal route (through the skin). Transdermal estrogen is</p><p>absorbed through the skin and directly enters the bloodstream,</p><p>bypassing the liver. Although clinical trials have yet to examine</p><p>transdermal estrogen thoroughly, observational data suggest that it is</p><p>less risky as compared to oral estrogen delivery. Transdermal</p><p>estrogen is available via a skin patch, gel, cream, or spray.</p><p>Systemic HRT is different from local estrogen therapy, which is applied</p><p>directly to the affected part and therefore has topical (local) effects. Low-</p><p>dose estrogen preparations are used to treat vaginal symptoms of</p><p>menopause, such as vaginal dryness, irritation, and pain. Topical estrogen is</p><p>given in creams, suppositories, gels, or rings that are inserted directly into</p><p>the vagina.</p><p>Estrogen preparations aren’t the only piece of the puzzle requiring</p><p>attention. It turns out that the type of progesterone can also make a</p><p>difference. This can take the form of progestin, which is a synthetic form of</p><p>the hormone, or progesterone itself, which is derived from natural sources.</p><p>The progestin used in the WHI trials is called MPA (medroxyprogesterone</p><p>acetate), and it has a problematic backstory of its own. Although MPA had</p><p>the uterine cancer risk covered, there’s reason to believe it may have been a</p><p>factor in the higher risk of breast cancer. Now, this observation doesn’t</p><p>mean that MPA was the only factor at play. Nonetheless, newer preparations</p><p>typically contain micronized progesterone, which, like the estradiol above,</p><p>is a molecular replica of the progesterone women make naturally, making it</p><p>bioidentical. Currently, there is little evidence that the combination of</p><p>bioidentical estrogen and progesterone increases the risk of breast cancer.</p><p>As a side note, while estrogen can be given in different ways, progesterone</p><p>is typically given orally.</p><p>Before we move forward, I want to take a moment to clarify a few things</p><p>about bioidentical hormones. The term bioidentical refers to hormones that</p><p>are a perfect replica of those made by women’s bodies. However, there are</p><p>some claims that bioidentical hormones may be “safer” or more effective</p><p>than other hormones. As long as we’re talking about formulations that are</p><p>FDA-approved and have been tested in rigorous clinical trials, other types</p><p>of hormones are perfectly safe to use.</p><p>Another potential source of confusion is that both government-approved</p><p>and compounded bioidentical hormones exist. In government-approved</p><p>preparations, each ingredient is regulated and monitored for purity and</p><p>efficacy, and tested for side effects. In contrast, compounded hormones</p><p>prepared by a compounding pharmacy can use untested formulations and</p><p>combine multiple hormones. They can also be administered in nonstandard</p><p>or untested routes, and are sometimes prescribed based on salivary or urine</p><p>hormone testing—a practice considered unreliable. Overall, the potential</p><p>benefits of bioidentical hormones can be achieved using conventionally</p><p>licensed products. Compounded bioidentical hormones may be a helpful</p><p>alternative in case of allergies to ingredients in a government-approved</p><p>formulation, or if specific dosages are not available. Now back to the WHI</p><p>and, most important, how to use HRT to our advantage!</p><p>Timing Is Everything</p><p>Another major concern about the WHI study boiled down to timing. After</p><p>years of investigating the investigation, we’ve come to recognize that the</p><p>risks and benefits of HRT vary based on two other essential factors: a</p><p>woman’s age and the length of time she’s been in menopause. This idea has</p><p>been coined the timing hypothesis. In the simplest possible terms,</p><p>estrogen’s effects seem to depend upon when we start taking it.</p><p>In the confident kickoff of HRT decades before the WHI took place, most</p><p>women went on hormones in their early fifties in response to menopausal</p><p>symptoms. Contrary to this real-life usage, the vast majority of participants</p><p>in the WHI were</p><p>postmenopausal women in their sixties and seventies, if</p><p>not older, and very few had any menopausal symptoms at all. This ten-to-</p><p>twenty-year gap would produce a world of difference. In fact, many</p><p>scientific studies have clarified that HRT works best while our bodies are</p><p>still receptive to estrogen. This receptivity occurs when a woman is in the</p><p>thick of menopause, and may extend as long as symptoms persist, but not</p><p>long after that period. During this critical menopausal window, estrogen can</p><p>improve and protect cellular health throughout the entire body. However, if</p><p>given long afterward, estrogen may no longer have the power to strengthen</p><p>or repair, but it may potentially cause detrimental effects. This fact clarifies</p><p>how HRT could benefit a woman in her fifties while having no effects on or</p><p>even harming a woman twenty years her senior.</p><p>Another factor worth considering: Given the age of the majority of</p><p>women in the WHI study, many might have already developed some of the</p><p>conditions the trial was looking to prevent. For example, since women’s</p><p>arteries have a higher propensity to harden after menopause, starting HRT</p><p>late in the game might have made hormone therapy less capable of</p><p>reversing or alleviating that problem. Since HRT also increases the risk of</p><p>blood clots and older women are more susceptible to blood clots to start</p><p>with, adding HRT into the mix may have contributed to the higher</p><p>occurrence of heart attacks. Similar concerns have been raised regarding the</p><p>increased risks of breast cancer and dementia.</p><p>Why, you might ask, would the most prominent drug trial in the history</p><p>of women’s health select women already long past menopause?</p><p>First off, when the WHI launched, precious little research had been done</p><p>to clarify how estrogen actually worked in a woman’s body and brain. If</p><p>you recall from chapter 2, these mechanisms were discovered a few years</p><p>after the WHI began. The timing hypothesis discussed above was</p><p>formulated a full decade later. So the WHI investigators were missing some</p><p>very important pieces of information. Additionally, as often happens in</p><p>research, the decision to enroll women in their sixties and older was made</p><p>on the basis of statistical considerations. The WHI was primarily designed</p><p>to test HRT for prevention of heart disease, but the trial was scheduled to</p><p>run for only eight to nine years. Since heart attacks and strokes tend to</p><p>make their appearance after menopause, the only way the WHI could</p><p>determine whether HRT could prevent those issues was by enrolling women</p><p>already old enough to reach that danger zone before the study’s time ran</p><p>out. Unfortunately, that plan backfired.</p><p>The decision to use oral CEEs and MPA as the only test hormones was</p><p>instead based in part on the limited HRT options back then and in part due</p><p>to financial considerations. Drug trials are expensive. Wyeth offered to</p><p>provide HRT free of charge for the entire trial, which was quite a deal.</p><p>Besides, those same hormones were already being used by millions of</p><p>women, so it made sense to test them in rigorous trials. And thank goodness</p><p>they did. Although this was not the WHI’s intention, the study revealed</p><p>something highly critical: putting older postmenopausal women on pills</p><p>containing high doses of oral CEEs and MPA (which was fairly standard</p><p>back then) was not a great idea.</p><p>These facts should have constituted the leads in the newspaper articles</p><p>instead of what most women heard on the news back in 2002. Further,</p><p>dozens of studies since then have provided reassurance that for healthy</p><p>women experiencing the symptoms of menopause, the benefits of taking</p><p>hormones—given at lower doses and often via the transdermal route—</p><p>generally outweigh the risks. However, these findings have trickled in, with</p><p>no one story gaining the same kind of exposure or momentum as reporting</p><p>on the WHI did. As a result, HRT’s reputation has never fully recovered,</p><p>and the consequences have been wide-reaching. With the old study still</p><p>ringing in our heads, most women remain understandably conflicted about</p><p>whether to use HRT for relief of their menopausal symptoms.</p><p>THE WINDOW OF OPPORTUNITY</p><p>If we’ve discovered there’s a time beyond which it’s best to avoid HRT,</p><p>what about when to start it? Is HRT safer for women younger than those</p><p>studied in the WHI—perimenopausal women and postmenopausal women</p><p>who still have symptoms, which is a sign that your body and brain are still</p><p>transitioning?</p><p>Today, the timing hypothesis is picking up steam. Scores of scientific</p><p>studies have shown that HRT started at the right time can lessen the</p><p>symptoms of menopause while also potentially protect against heart disease</p><p>and other chronic conditions. For instance, studies of monkeys have shown</p><p>that estrogen can be a strong protectant against heart disease when it’s given</p><p>during monkey menopause. When estrogen is administered to primates the</p><p>equivalent of six human years after this period, it offers no protective effect</p><p>—the window has passed. Scientists using mice to find a cure for</p><p>Alzheimer’s disease are discovering a similar pattern. When estrogen is</p><p>given to perimenopausal or recently postmenopausal mice, it spurs cell</p><p>growth, supports brain function, and can even prevent the formation of</p><p>Alzheimer’s plaques. But when given too long after menopause, HRT</p><p>provides no benefit and may be harmful to the animals instead.</p><p>Overall, several lines of evidence suggest that HRT might be beneficial</p><p>against these conditions when started early. For instance, the WHI did</p><p>include a small percentage of women who were in their fifties, or more</p><p>generally within ten years of the onset of menopause, when the studies</p><p>began. For those women, HRT was associated with a reduced risk of heart</p><p>attacks and deaths from heart disease and an overall lower mortality rate</p><p>than those who did not take hormones. There is also emerging evidence that</p><p>HRT may protect against cognitive decline, at least for some women, an</p><p>issue we’ll discuss in greater detail later. Thankfully, a growing number of</p><p>positive observations such as these have led to a change of heart about how</p><p>to use HRT for clinical practice.</p><p>Updated Guidelines for HRT Use</p><p>Until recently, most professional societies recommended extreme caution</p><p>when taking HRT. Women were advised to use HRT for a limited number of</p><p>symptoms, at the lowest possible dose, and for the shortest amount of time.</p><p>Then in 2022, after thorough review of many positive findings that had</p><p>accumulated over time, the North American Menopause Society published</p><p>an updated position statement including striking revisions about the risks</p><p>and benefits of HRT. These revisions, which have been endorsed by another</p><p>twenty international organizations, grant more flexibility while also taking</p><p>into consideration that every woman is different. Let’s review these</p><p>important updates.</p><p>Is HRT a Breast Cancer Risk?</p><p>The number one question for every woman approaching menopause is</p><p>whether estrogen replacement will increase their breast cancer risk. Do I go</p><p>on hormones and get rid of the hot flashes but risk cancer—or pass on HRT,</p><p>soldier on, and hope that eventually the symptoms go away?</p><p>As we’ve discussed, these concerns were instigated by the WHI results;</p><p>specifically, the 26 percent increased risk of breast cancer observed with the</p><p>estrogen-plus-progestin formulation. Once again, let’s return to the fine</p><p>print. Out of the entire cohort, 38 women taking HRT developed breast</p><p>cancer, compared to 30 in the placebo group. If you do some simple math,</p><p>that’s 26 percent more cases. However, in actual numbers, taking HRT</p><p>resulted in only 8 more cases of breast cancer in total. So another way to</p><p>think about this is that for every 10,000 women taking hormones (i.e., that</p><p>specific combination of oral CEE plus progestin), an additional 8 developed</p><p>breast cancer. These are much less striking odds than implied by a 26</p><p>percent increased risk.</p><p>Another thing worth considering is that the increase in breast cancer risk</p><p>emerged only after five years of treatment—and twenty years later, the</p><p>mortality rate of women taking hormones was no higher than that of the</p><p>placebo group. And let’s not forget about the other WHI trial, in which the</p><p>estrogen-only treatment for women with hysterectomies resulted in 7 fewer</p><p>breast cancer cases than placebo—that’s a 24 percent reduction. These are</p><p>important nuances we don’t hear about enough.</p><p>Based on these and additional data collected after the WHI ended, most</p><p>professional societies now agree that the overall risk of breast cancer related</p><p>to HRT is in fact low, with current guidelines defining it as a “rare</p><p>occurrence.” In the words of Dr.JoAnn Pinkerton, executive director of the</p><p>North American Menopause Society, “Most healthy women under age 60 or</p><p>within ten years of having their last period can take hormone therapy</p><p>without fear if taking estrogen alone or combined with progesterone.”[*]</p><p>When started within this time frame, HRT can be helpful to alleviate many</p><p>symptoms of menopause, and it has been associated with a reduced risk of</p><p>hip fracture, heart disease, colorectal cancer, and diabetes mellitus in the</p><p>long term, too. A caveat here: This is contingent upon there being no</p><p>previous history of breast cancer, as the risk of cancer reoccurrence remains</p><p>a concern. If this is an urgent concern, skip to chapter 11, which is</p><p>specifically focused on this topic. For cancer-free women, let’s look at some</p><p>numbers:</p><p>Estrogen-plus-progesterone therapy does not significantly increase</p><p>the risk of breast cancer in the short term (less than five years), but</p><p>it is associated with a relatively small increase in risk over the long</p><p>term (over five years). This increase is more closely associated with</p><p>oral CEEs combined with MPA (the synthetic form of progesterone</p><p>used in the WHI) than newer formulations, such as bioidentical</p><p>estrogen and progesterone.</p><p>Estrogen-only therapy does not increase the risk of breast cancer for</p><p>cancer-free women without a uterus—that is to say, those who have</p><p>had a hysterectomy—when taken for up to ten years. While we</p><p>don’t have enough definitive data after this ten-year window,</p><p>observational studies suggest the risk of cancer may remain low for</p><p>longer times.</p><p>Vaginal (topical) estrogen has not been linked with an increased risk</p><p>of breast cancer in the short or long term.</p><p>Another helpful thing to do is to put the risk of breast cancer associated</p><p>with HRT into context. In fact, there are several common medical and</p><p>lifestyle factors that pose a similar or greater risk of breast cancer compared</p><p>to HRT. For example, simply leading a sedentary life carries a similar risk</p><p>of breast cancer as HRT. But also, consuming two glasses of wine per day</p><p>or carrying significant excess weight can double the risk of breast cancer</p><p>compared to any form of HRT. Therefore, while the discussion around HRT</p><p>and cancer risk is crucial, it’s equally important to consider this within the</p><p>larger picture of overall health, lifestyle, and medical choices.</p><p>Short-Term vs. Long-Term Use</p><p>For many years, professional guidelines stated that one should use the</p><p>lowest dose of HRT for the shortest amount of time needed to keep the</p><p>symptoms under control, and even then, only when indicated. The medical</p><p>community now acknowledges that position may have been inadequate and</p><p>even harmful for some women. Today, there is consensus that HRT does not</p><p>need to be routinely discontinued in those older than sixty, especially in the</p><p>presence of persistent menopausal symptoms or quality-of-life issues.</p><p>According to professional societies, the data no longer support that cutoff</p><p>and arbitrary limits should not be placed on the duration of treatment if</p><p>symptoms persist, though an individualized reevaluation of risks and</p><p>benefits is always recommended.</p><p>Spontaneous, Early, and Surgical Menopause</p><p>The biggest takeaway from the last two decades of research is that age</p><p>matters. Contrary to popular knowledge, hormone therapy is actually</p><p>recommended for women who go through menopause early, in the absence</p><p>of contraindications. HRT can be beneficial for those with premature or</p><p>early menopause resulting from genetic factors, primary ovarian</p><p>insufficiency (POI), or autoimmune or metabolic disorders, and particularly</p><p>in case of surgical menopause following oophorectomy. Surgical</p><p>menopause is a far more challenging experience for most women compared</p><p>to spontaneous menopause. Unfortunately, little thought or preparation is</p><p>given to those undergoing this procedure, who are often left in the dark as</p><p>to what happens afterward. So it’s really important to underline that HRT is</p><p>a viable choice for many women experiencing early menopause following</p><p>oophorectomy. Experts believe that eligible patients should be encouraged</p><p>to start HRT as soon as possible after surgery and to stay on HRT at least</p><p>until the average age of menopause, approximately age fifty-one. This</p><p>regimen has been shown to effectively treat hot flashes and vaginal</p><p>discomfort, and to protect against bone loss. Observational data also show</p><p>that estrogen therapy, along with progesterone if the uterus is present, may</p><p>reduce the risk of future heart disease and cognitive impairment after</p><p>oophorectomy.</p><p>Starting HRT After Menopause</p><p>What if you are over sixty years old or more than ten years past</p><p>menopause? Is it safe to start HRT then? Considering everything we know</p><p>and don’t know from the research, this requires careful consideration. If</p><p>there’s one thing we’ve learned from the WHI, it is that starting high-dose</p><p>oral estrogen long after menopause might increase the risk of some chronic</p><p>conditions, such as heart disease. If HRT is to be started after age sixty or</p><p>more than ten years past menopause, professional societies recommend low</p><p>doses of hormones and preferably transdermal options like the patch or gel</p><p>to alleviate persistent menopausal symptoms or quality-of-life issues. In the</p><p>absence of rare contraindications, vaginal estrogen can be started at any</p><p>age.</p><p>Contraindications vs. Approved Indications for HRT</p><p>Contraindications for systemic hormone therapy currently include:</p><p>Pregnancy</p><p>Unexplained or abnormal vaginal bleeding</p><p>Active liver disease</p><p>Uncontrolled hypertension (high blood pressure)</p><p>Known or suspected hormone-sensitive cancer, such as breast cancer</p><p>Current treatment for breast cancer</p><p>Active or recent arterial thromboembolic disease (that is to say, a</p><p>blood clot that develops in an artery)</p><p>Previous or current venous thromboembolism (VTE; that is to say,</p><p>blood clots in the veins, the legs, or the lungs)</p><p>Previous or current coronary heart disease or coronary artery disease,</p><p>stroke, or myocardial infarction</p><p>There may, however, be exceptions based on personal medical history,</p><p>which are important to discuss with your provider. For example, having had</p><p>a blood clot is considered a “soft” contraindication that requires further</p><p>evaluation. The route of HRT administration can also make a difference, as</p><p>the risk of stroke and blood clots is lower with transdermal routes.</p><p>Importantly, having a family history of any of the above conditions is not a</p><p>contraindication, though it warrants medical review. To clarify this concept,</p><p>hormones are not usually recommended if you personally have (or had)</p><p>estrogen-dependent cancer—not because someone in your family has (or</p><p>had) breast cancer.</p><p>For eligible women, HRT is not only recommended but FDA-approved</p><p>for:</p><p>▷ VASOMOTOR SYMPTOMS</p><p>HRT remains the most effective first-line treatment for relief of moderate to</p><p>severe vasomotor symptoms of menopause, aka hot flashes and night</p><p>sweats. In clinical trials, both estrogen-alone and estrogen-plus-</p><p>progesterone regimens reduced the number of hot flashes by about 75</p><p>percent while also reducing their intensity. Transdermal formulations seem</p><p>to be as effective as oral options.</p><p>▷ PREVENTION OF OSTEOPOROSIS</p><p>HRT has been shown to prevent bone loss and reduce fractures in women</p><p>without osteoporosis. If one already has osteoporosis, other medications are</p><p>best.</p><p>▷ GENITOURINARY (GENITAL-URINARY) SYMPTOMS</p><p>The genitourinary syndrome of menopause (GSM)</p><p>your</p><p>brain that’s at the wheel.</p><p>Does that make your worst fear real? Are you truly losing your mind?</p><p>Not at all. I am here to reassure you that you are not going crazy. Most</p><p>important to note: you are not alone in this, and you are going to be okay.</p><p>While menopause does indeed impact the brain, that doesn’t mean the</p><p>problems we experience are “all in our head.” Just the opposite.</p><p>THE HIDDEN SCALE AND IMPACT OF MENOPAUSE</p><p>In our youth-obsessed culture, where it’s not outright dismissed, menopause</p><p>is either dreaded or derided. Not only is there no acknowledgment of</p><p>menopause as a noteworthy landmark in a woman’s life, but as it is</p><p>historically perceived in the extreme negative, menopause comes with the</p><p>stigmas associated with ageism, the demise of one’s vitality, and even the</p><p>end of our identity as women. Mostly, however, menopause is framed in</p><p>silence, sometimes even secrecy. Generations of women have suffered</p><p>under misinformation, shame, and helplessness. Many remain reluctant to</p><p>discuss their symptoms for fear of being judged, or strive to hide them.</p><p>Most don’t even realize that what they’re experiencing has anything to do</p><p>with menopause in the first place.</p><p>All this confusion isn’t just unfair. It constitutes a significant public</p><p>health problem, with far-reaching consequences. Let’s look at the numbers:</p><p>Women are half of the population.</p><p>All women go through menopause.</p><p>Women of menopausal age are by far the largest growing</p><p>demographic group. By 2030, 1 billion women worldwide will have</p><p>entered or will be about to enter menopause.</p><p>Most women spend about 40 percent of their lives in menopause.</p><p>All women, menopausal or not, possess an organ that has been</p><p>largely ignored: the brain.</p><p>Over three-quarters of all women develop brain symptoms during</p><p>menopause.</p><p>Out of sheer numbers alone, menopause should be a major sociocultural</p><p>event and the subject of extensive investigation and deep knowledge.</p><p>Instead, whether we remain focused on the unpleasant symptoms or</p><p>psyched out by the perceived lessening of our female powers, the current</p><p>perception of what menopause means is fixated on the many pitfalls of this</p><p>life event. Meanwhile, from a scientific and a medical perspective, it’s a</p><p>discipline without a name.</p><p>The Problem of Western Medical Frameworks</p><p>Thanks to how genuinely uninformed we are about menopause, too many</p><p>women are caught completely off guard, feeling betrayed by their body and</p><p>their brain—not to mention their doctors, too. While hot flashes are</p><p>generally recognized as a “side effect” of menopause, most doctors simply</p><p>won’t make the connection between menopause and its other symptoms</p><p>such as anxiety, insomnia, depression, or brain fog. This is especially the</p><p>case for women under fifty, who are typically sent home with a prescription</p><p>for antidepressants, their concerns dismissed as a by-product of their</p><p>psychology, a sort of female existential crisis. Why is that?</p><p>Western medicine is well known for its siloed, non-holistic frameworks,</p><p>in which the human body is evaluated in terms of its individual</p><p>components. For example, people with eye problems go to an eye doctor,</p><p>and those with heart problems go to a cardiologist even if the heart</p><p>problems led to the eye problems. As a result of this extreme specialization,</p><p>menopause has been pigeonholed as “an issue with the ovaries” and</p><p>consigned to ob-gyn territory. Anyone who’s been there, however, knows</p><p>that ob-gyns don’t do brains. Educated like every other doctor to specialize</p><p>in specific body parts—in this case, the reproductive system—they aren’t</p><p>trained to diagnose or manage brain symptoms in the first place. But also,</p><p>many ob-gyns are not trained to manage menopause at all. Today, fewer</p><p>than one in five ob-gyn residents receive formal training in menopause</p><p>medicine, which often consists of a mere few hours in total. Perhaps</p><p>unsurprisingly, 75 percent of women who seek care for menopausal</p><p>symptoms end up not receiving treatment.</p><p>On the other hand, brain doctors—neurologists and psychiatrists, among</p><p>others—don’t handle menopause, either. Given these divided frameworks,</p><p>it’s no surprise that the effects of menopause on brain health have been</p><p>neglected, leaving these issues to fall into the cracks between rigidly</p><p>defined medical disciplines.</p><p>Here’s where brain scientists come in handy. I am one of them, holding a</p><p>somewhat unusual PhD in neuroscience (the study of how the brain works)</p><p>and nuclear medicine (a branch of radiology that uses imaging techniques to</p><p>examine the brain). But what really sets my work apart is that I have made</p><p>it my life’s work to study and support women’s brains. Specifically, I am an</p><p>associate professor of neuroscience in neurology and radiology at Weill</p><p>Cornell Medicine in New York City, where I apply this background at the</p><p>intersection of all these disciplines and women’s health. To this aim, in</p><p>2017, I launched the Women’s Brain Initiative, a clinical research program</p><p>entirely and unapologetically dedicated to understanding how brain health</p><p>plays out differently in women than in men. All day every day, my team</p><p>studies women’s brains—how they work, what makes them uniquely</p><p>powerful, what makes them uniquely vulnerable. At the same time, I am the</p><p>director of the entire Alzheimer’s Prevention Program at Weill Cornell</p><p>Medicine/NewYork-Presbyterian, which allows me to integrate my research</p><p>on women’s brains with the clinical practice of evaluating and supporting</p><p>cognitive and mental health for the long run.</p><p>Years of research have made clear to me that caring for the health of the</p><p>female brain requires a careful understanding of how it shifts and changes</p><p>in response to our hormones, especially during menopause. So one of the</p><p>very first things I did after launching these programs was to pick up the</p><p>phone and call the ob-gyn department. From that day on, we’ve been</p><p>collaborating with some of the best menopause specialists around, as well</p><p>as top-tier ob-gyn surgeons and oncologists. Together we set out to answer</p><p>the question we didn’t see enough professionals exploring: How does</p><p>menopause impact the brain?</p><p>THE BRAIN ON MENOPAUSE</p><p>When I started studying menopause, I quickly realized two important facts.</p><p>First, very few brain studies looked at menopause at all. Second, the few</p><p>that did were focused on women who were well past menopause, often in</p><p>their sixties and seventies. In other words, menopause has been studied in</p><p>terms of its impact on the brain after the fact—more like a product than a</p><p>process.</p><p>My team and I have focused instead on what leads to those outcomes, up</p><p>to and through menopause. To give you a sense of how dire the situation</p><p>looked when we started, there wasn’t a single study that examined women’s</p><p>brains before and after menopause. So we rolled up our sleeves, turned on</p><p>the brain scanner, and set out to explore this new frontier. As of today,</p><p>we’ve made significant progress in demonstrating that women’s brains age</p><p>differently from men’s brains, and that menopause plays a key role here. In</p><p>fact, our studies have shown that menopause is a neurologically active</p><p>process that impacts the brain in fairly unique ways.</p><p>Figure 1. Brain scans before and after menopause</p><p>To give you a sense of this, what you see on the previous page is a type</p><p>of brain scan generated by a functional imaging technique called positron</p><p>emission tomography, or PET, that measures brain energy levels. Brighter</p><p>colors indicate high brain-energy levels, while the darker patches indicate a</p><p>lower energy turnover. (For full-color imagery, see my website:</p><p>https://www.lisamosconi.com/projects.)</p><p>The image to the left shows a high-energy brain. It is a perfect example</p><p>of what you want your brain to look like when you’re in your forties—vivid</p><p>and bright. This brain belongs to a woman who was forty-three years old</p><p>when scanned for the first time. Back then, she had a regular cycle and no</p><p>symptoms of menopause.</p><p>Now look at the scan labeled postmenopause. That’s the same brain just</p><p>eight years later, shortly after the woman had gone through</p><p>includes vaginal</p><p>dryness, burning, and irritation, pain and diminished lubrication with sexual</p><p>activity, as well as urinary incontinence, overactive bladder, and recurrent</p><p>urinary tract infections (UTIs). The preferred treatment is low-dose vaginal</p><p>estrogen dispensed as creams, tablets, rings, and soft gel vaginal inserts that</p><p>you can apply to the vaginal area to reduce chafing, dryness, and tissue</p><p>thinning. Regrettably, only 25 percent of women suffering from vaginal</p><p>atrophy use this treatment, partly due to concerns around breast cancer.</p><p>That’s in part because of the FDA’s inclusion of a black-box warning on the</p><p>package label, which has further discouraged both doctors and patients from</p><p>considering this option. However, these warnings are based on the findings</p><p>of the WHI, which did not assess the use of vaginal estrogen at all. So, let</p><p>me repeat this: low-dose vaginal estrogen has not been linked with an</p><p>increased risk of cancer. In some rare cases, some patients may not be</p><p>eligible for local estrogen, in which case the first-line treatment is a</p><p>nonhormonal vaginal moisturizer. Note that vaginal estrogen may not</p><p>increase libido or sexual interest. Systemic HRT is best in this case, and</p><p>transdermal estrogen formulations may be preferred to oral. Testosterone</p><p>therapy is another option, which we’ll discuss in the next chapter.</p><p>Other Indications</p><p>Although HRT is not currently FDA-approved for changes in sleep, mood,</p><p>or cognitive performance during menopause, many clinicians prescribe it</p><p>based on reports of its beneficial effects, especially during the hormonal</p><p>upheaval of the perimenopausal years. Specifically:</p><p>▷ SLEEP DISTURBANCES</p><p>Although more evidence is needed, several studies indicate that low-dose</p><p>estrogen with or without progesterone may reduce sleep disturbances in</p><p>perimenopausal women, in part by reducing night sweats, while also</p><p>improving insomnia in postmenopausal women.</p><p>▷ DEPRESSIVE SYMPTOMS</p><p>In this case, it’s important to first clarify whether the symptoms are a result</p><p>of perimenopausal depression or major depression. Is it a hormonal</p><p>response, or another underlying cause? The appropriate treatment will vary</p><p>accordingly. Antidepressants or psychotherapy are the primary treatment for</p><p>major depression, whereas estrogen therapy is the first-line treatment for</p><p>mild depressive symptoms associated with perimenopause. It produces</p><p>effects similar to antidepressant medications while also targeting the root</p><p>cause of these symptoms. Estrogen therapy can be taken in combination</p><p>with antidepressants if needed. However, estrogen therapy is not</p><p>recommended for severe depressive symptoms, so it is important to consult</p><p>with a qualified healthcare professional to make an informed decision.</p><p>According to current guidelines, HRT may not be effective as a treatment</p><p>for depression after menopause, although it may help improve the clinical</p><p>response to antidepressants, especially for postmenopausal women who are</p><p>still experiencing hot flashes.</p><p>▷ BRAIN FOG AND FORGETFULNESS</p><p>As is apparent, women’s cognitive health is at the heart of my work, so of</p><p>course I looked into HRT for memory support and dementia prevention.</p><p>First off, can HRT conceivably improve the perimenopausal dip in</p><p>cognitive function? The results are encouraging, as there is evidence that</p><p>estrogen therapy started during perimenopause or early menopause can</p><p>support and even enhance some aspects of cognition, primarily memory.</p><p>While more rigorous research is needed, HRT seems to help with brain fog</p><p>and forgetfulness, at least for some women. These beneficial effects are</p><p>particularly evident for those undergoing hysterectomy or oophorectomy</p><p>procedures.</p><p>The other big question is: Can HRT prevent dementia later in life?</p><p>Unfortunately, the WHI remains the only clinical trial testing HRT effects</p><p>for dementia prevention. As you know, those studies looked at women who</p><p>were already postmenopausal by a long shot. Perhaps unsurprisingly, they</p><p>showed no effects or even detrimental effects depending on the type of HRT</p><p>used. The combination of oral CEEs plus MPA increased the risk of</p><p>dementia when started in postmenopausal women in their late sixties or</p><p>older. On the other hand, estrogen-alone therapy did not increase the risk of</p><p>dementia relative to placebo, which is reassuring but still not the answer</p><p>we’re hoping for. Two important things to keep in mind are that we don’t</p><p>know whether other HRT formulations might yield different results and that</p><p>the women to test are the ones in the thick of menopause, not those decades</p><p>past it.</p><p>Unfortunately, clinical trials of younger women receiving HRT when the</p><p>therapy is more likely to work, which is during the transition to menopause</p><p>or soon after, are lacking. There hasn’t been a single clinical trial of</p><p>hormone therapy for dementia prevention among women in perimenopause,</p><p>which is simply unacceptable. Nonetheless, reexaminations of the fewer</p><p>younger women (those fifty to fifty-nine) included in the WHI provided</p><p>important evidence that HRT started in midlife may indeed help to reduce</p><p>the risk of dementia. Results show that, as these women got older, those</p><p>taking estrogen in midlife didn’t develop cognitive declines nearly as often</p><p>as those given a placebo. Several observational studies report similar</p><p>findings, prompting many clinicians to advocate for taking HRT during</p><p>perimenopause or early menopause to sustain neurological health in older</p><p>age. For now, in the absence of more definitive findings, HRT is not</p><p>recommended to prevent or treat cognitive decline or dementia. While</p><p>we’re not there yet, I hope these recommendations will further shift and</p><p>evolve as we gather more evidence.</p><p>The Next Generation of HRT: Designer Estrogens</p><p>When it comes to HRT, many feel like they have to take sides. Opt in or opt</p><p>out? Take it or leave it? As the ping-pong match around this topic remains</p><p>endless, women are effectively being asked to choose between their breasts</p><p>and their brains. As a scientist, I believe we’re asking the wrong question.</p><p>We don’t need to make do with quantifying trade-offs of what’s currently</p><p>available—we need better solutions. The question we should be asking is:</p><p>Could we develop a type of HRT that is proven to support brain function</p><p>and does not increase the risk of cancer? Sounds too simple or too good to</p><p>be true?</p><p>Enter the new generation of so-called designer estrogens. This is to say,</p><p>estrogens that are designed to do what women need. These compounds are</p><p>called SERMs, which stands for selective estrogen receptor modulators.</p><p>SERMs can block estrogen effects in certain parts of the body while acting</p><p>like estrogen and potentiating its effects in other parts. By doing so, SERMs</p><p>can offer many of estrogen’s benefits without some of its possible risks.</p><p>Many SERMs are available in clinical practice. For example, a SERM</p><p>called tamoxifen is commonly used as a first-line treatment for breast</p><p>cancer. Tamoxifen blocks estrogen receptors in breast tissue, effectively</p><p>stopping estrogen from binding to cancer cells in the breast and making</p><p>them grow. At the same time, however, it mimics estrogen effects in other</p><p>parts of the body, like in the bones, where it may have positive effects. It’s</p><p>this ability to block estrogen in certain areas of the body while activating it</p><p>in others that makes SERMs... selective.</p><p>After years of rigorous research, Dr.Roberta Diaz Brinton (my mentor</p><p>and colleague) succeeded in developing a SERM for the brain. It is called</p><p>PhytoSERM. Phyto means that the estrogen comes from plants. This genius</p><p>formulation was developed to selectively supply estrogen to the brain, while</p><p>being largely inactive or even inhibitory in reproductive tissue—that is to</p><p>say, it does not increase the risk of breast or uterine cancer. You can think of</p><p>PhytoSERM as a plant-based estrogen GPS for the brain: it bypasses the</p><p>reproductive organs, making a beeline to deliver all the benefits of estrogen</p><p>directly to the brain. In 2022, in collaboration with Dr. Brinton, we</p><p>launched an NIH-sponsored, randomized,</p><p>placebo-controlled clinical trial</p><p>(read, a very thorough clinical trial) to test PhytoSERM for support of brain</p><p>energy and cognitive function in perimenopausal and early menopausal</p><p>women. This launch shows exciting promise. With clinical validation, we</p><p>are hoping this estrogenic formulation will prove valuable not only to</p><p>address the symptoms of menopause but also to provide extra protection for</p><p>our brains, shielding them against dementia in particular. The trial results</p><p>should be available around 2025, which, judging by how fast time is flying,</p><p>is right around the corner.[*]</p><p>MAKING AN INFORMED DECISION</p><p>It is fair to say that menopausal women have been underserved—an</p><p>oversight that should be considered one of the great blind spots of medicine.</p><p>But as increasing research provides a more reliable picture of the risks and</p><p>benefits of HRT, things are looking a lot less grim than in the past twenty</p><p>years. It’s time to replace fear not only with knowledge but also with</p><p>innovation. For many years, the decision of whether to take HRT was based</p><p>on the one-size-fits-all approach of randomized clinical trials. It is now</p><p>understood that each person needs customized attention, with continued</p><p>evaluation of their own outcomes. Obviously breast cancer risk is an</p><p>important factor to consider, but so are symptom control and quality of life</p><p>—and every woman has not only different concerns but also different</p><p>preferences and different levels of risk tolerance. There should be a holistic</p><p>and individualized approach to managing menopause, perusing</p><p>comprehensive, unbiased advice about the role of HRT as well as the full</p><p>menu of lifestyle factors and nonhormonal remedies available to us.</p><p>For many women, the proper introduction of hormones can be nothing</p><p>less than a godsend. But while it is necessary to modernize our</p><p>understanding of HRT, it is just as important to underline that estrogen is</p><p>not a magic bullet or miracle cure. While I totally understand the desire to</p><p>offer HRT to women for whom it is indicated, the blanket use of HRT is not</p><p>supported by science or the guidelines of the medical societies invested in</p><p>menopause, and risks bringing us right back to the 1960s. There are many</p><p>moving parts involved in working out the risks and rewards, and anyone</p><p>who thinks there’s a bumper-sticker answer to this question is neither</p><p>listening to scientific argument nor reading the fine print. Estrogen can do</p><p>many things—it can help with hot flashes, sleep disturbance due to hot</p><p>flashes, low mood in early menopause, and osteoporosis prevention.</p><p>Vaginal estrogen can help if sex is painful and for recurrent bladder</p><p>infections. However, we need more research before HRT can be used for</p><p>prevention or treatment of other medical conditions such as heart disease,</p><p>severe depression, or dementia. Additionally, HRT simply doesn’t work for</p><p>everyone, no matter the type or dose.</p><p>Moreover, while it is important that we reevaluate HRT as a viable option</p><p>for menopause care, women who are unable to take HRT due to medical</p><p>conditions or side effects, those who don’t require HRT, those who feel bad</p><p>on it, and those who prefer not to take hormones may be feeling dismayed</p><p>or left out. So I want to emphasize that respect for the diversity of women’s</p><p>health experiences and choices is extremely important. There is no one size</p><p>fits all. All of us deserve to make our own choice armed with knowledge</p><p>and options to do so. From nonhormonal prescription medications to</p><p>lifestyle changes, there are other methods of managing menopausal</p><p>symptoms, improving quality of life, and supporting overall brain health,</p><p>which we’ll discuss in the next pages. Remember, only you know what’s</p><p>right for you.</p><p>10</p><p>Other Hormonal and Nonhormonal</p><p>Therapies</p><p>WEIGHING OUR OPTIONS</p><p>As we’ve explored the landscape of menopause throughout the last</p><p>chapters, it’s clear that one’s experience of menopause is as unique as one’s</p><p>thumbprint. The methods of finding relief from its bothersome symptoms</p><p>can be just as individualized. In recent years, the resurgence in HRT’s</p><p>popularity has brought comfort and relief to many women who experience</p><p>menopause-related symptoms. However, although HRT may be the most</p><p>well-known remedy, it’s not the only game in town.</p><p>In this chapter, we’ll delve into additional pharmaceutical options for</p><p>treatment of menopausal symptoms. These include some hormonal</p><p>therapies, such as testosterone therapy and birth control, as well as</p><p>nonhormonal prescription medications. Nonhormonal management is an</p><p>especially important possibility when hormones are not an option due to</p><p>medical contraindications such as hormone-dependent cancers. In light of</p><p>the recent emphasis on promoting HRT, cancer patients—who may already</p><p>be coping with the physical and emotional stressors of their diagnosis and</p><p>treatment—may feel excluded or as if they’re being offered inferior options</p><p>instead of the real deal. It is therefore important to underline that</p><p>nonhormonal medications provide a solid alternative for managing</p><p>menopausal symptoms. For example, paroxetine, an antidepressant</p><p>medication, is approved by the U.S. Food and Drug Administration (FDA)</p><p>for managing hot flashes. Other antidepressants, as well as medications like</p><p>gabapentin and clonidine, also show evidence of efficacy in relieving</p><p>menopausal symptoms. Just recently, in 2023, the FDA approved</p><p>fezolinetant, a novel nonhormonal medication designed to treat moderate to</p><p>severe hot flashes. Discussing all available options is essential to ensure</p><p>that all women have access to appropriate and effective treatments for their</p><p>own individual needs and circumstances.</p><p>Testosterone Therapy</p><p>As women enter menopause, hot flashes, mood swings, reduced energy, and</p><p>low libido can crash the party, leaving many searching for relief. Enter</p><p>testosterone, the hormone equivalent of a bouncer, ready to kick those</p><p>pesky symptoms to the curb. But is testosterone really a reliable</p><p>bodyguard?</p><p>While testosterone is typically regarded as a male hormone, women need</p><p>it, too. In fact, our bodies produce three times as much testosterone as</p><p>estrogen before menopause, in part because testosterone is needed to make</p><p>estrogen in the first place. Testosterone is made by the ovaries, as well as by</p><p>the adrenal glands and fatty tissue throughout the body. Because of this, its</p><p>levels don’t decline as much as estradiol levels do after menopause.</p><p>Nonetheless, with aging, testosterone does decline, too, oftentimes taking</p><p>sex drive along for the ride. Women with low testosterone levels may also</p><p>experience symptoms of anxiety, irritability, depression, fatigue, memory</p><p>changes, and insomnia. Additionally, while it is true that testosterone</p><p>declines are typically due to the aging process rather than to spontaneous</p><p>menopause, induced menopause can be associated with a much more abrupt</p><p>loss of testosterone, which can be quite challenging. Women with primary</p><p>ovarian insufficiency (POI) may also experience more severe reductions in</p><p>testosterone levels. These differences are too often overlooked when</p><p>evaluating treatment options.</p><p>Currently, the only clinical indication for prescribing testosterone is low</p><p>libido. This is based on many studies and clinical trials showing that</p><p>testosterone therapy can be effective to increase sexual desire, satisfaction,</p><p>and pleasure after menopause. More often than not, HRT is enough to</p><p>alleviate these concerns. However, if after a few months on HRT you are</p><p>still experiencing loss of libido, as well as tiredness and fatigue, then it’s</p><p>worth having a conversation with your doctor about adding testosterone to</p><p>your HRT regime. According to current guidelines, testosterone therapy in</p><p>addition to HRT is considered appropriate if:</p><p>You are postmenopausal, taking estrogen therapy, and have a</p><p>decreased sex drive with no other identifiable causes.</p><p>You have reduced sex drive, depression, and fatigue after surgically</p><p>induced menopause, and estrogen therapy hasn’t relieved your</p><p>symptoms.</p><p>Although these guidelines don’t specifically address perimenopause,</p><p>there is no reason why younger women wouldn’t benefit from testosterone</p><p>therapy, too. This is particularly relevant considering that changes in libido</p><p>often occur early in the course of the menopause transition.</p><p>Testosterone is currently not recommended to improve mood or</p><p>cognition. Despite what you may have heard on the news, testosterone</p><p>therapy for support of cognitive function in particular remains as</p><p>controversial as pineapple on pizza. Here’s why: While some studies have</p><p>suggested that testosterone may have a positive impact on cognitive</p><p>function, the available evidence is very limited. On the one hand, a few</p><p>small-scale clinical trials have shown improvement in some aspects of</p><p>cognition in postmenopausal women treated with testosterone as compared</p><p>to those in a placebo-treated group. On the other hand, just as many small</p><p>studies have reported no improvement. Studies examining testosterone’s</p><p>effects on mood in women are even more scant. In summary, we don’t have</p><p>enough evidence regarding these potential benefits to draw firm</p><p>conclusions. As always, we need more research!</p><p>If you are interested in trying testosterone, here are three things to keep</p><p>in mind. First, testosterone therapy for menopause typically involves</p><p>administering a low dose of the hormone transdermally, through a patch,</p><p>gel, or cream. Second, you don’t need a blood test to decide whether</p><p>testosterone is a good choice for you. That’s because a low testosterone</p><p>level in blood doesn’t correlate with low libido or other symptoms. This</p><p>also means that you don’t need to start testosterone if your blood level is</p><p>low. If you decide to start therapy, though, it may be helpful to check your</p><p>testosterone levels over time to adjust treatment as needed. An annual</p><p>review with your doctor is also recommended to look at symptom</p><p>management and be informed about your own risks and benefits at any</p><p>given time. Third, if you have libido-related concerns, many providers also</p><p>recommend treating any vaginal dryness or discomfort with vaginal</p><p>estrogen or other remedies. If there is pain with sex, it is recommended that</p><p>you have your pelvic floor examined by a specialist and address any</p><p>discomfort or pain before starting medications for libido.</p><p>Finally, while some women experience benefits from testosterone</p><p>therapy, it is essential to carefully weigh the potential risks and benefits on</p><p>a case-by-case basis. More rigorous work is also needed to provide clear</p><p>evidence supporting testosterone therapy’s long-term efficacy and safety,</p><p>especially concerning its effects on breast and endometrial tissue. On the</p><p>upside, testosterone therapy carries few side effects, chiefly an increase in</p><p>body hair at the site of application. Contrary to popular belief, scalp hair</p><p>loss, acne, and hirsutism are uncommon effects, as is deepening of the</p><p>voice.</p><p>Birth Control</p><p>Another way to manage some menopausal symptoms may be a treatment</p><p>you thought you were perhaps done with: birth control. While the primary</p><p>purpose of contraceptives is to prevent pregnancy, hormonal birth control</p><p>methods, such as combined oral contraceptives (COCs), progestin-only</p><p>pills, and hormonal intrauterine devices (IUDs), all deliver small doses of</p><p>estrogen and/or progesterone that can help regulate hormone levels, with</p><p>balancing effects on the menstrual cycle. This can help reduce bleeding and</p><p>menstrual cramps, and alleviate symptoms of conditions like polycystic</p><p>ovary syndrome (PCOS) and endometriosis in turn. (Note: The intrauterine</p><p>copper device, or IUCD, is hormone-free and not covered here.)</p><p>Here’s how hormonal birth control can help during menopause:</p><p>Menstrual cycle regulation. By providing a consistent supply of</p><p>hormones, hormonal contraceptives can help regulate menstrual</p><p>cycles and reduce the irregular bleeding experienced during</p><p>perimenopause.</p><p>Hot flash reduction. Clinical trials have shown that low-dose oral</p><p>contraceptives can reduce the frequency and severity of hot flashes</p><p>and night sweats. In several studies of perimenopausal women,</p><p>those who received a low-dose oral contraceptive experienced an</p><p>average 25 percent reduction in vasomotor symptoms.</p><p>Bone health. Oral contraceptives taken during perimenopause can</p><p>help increase bone density, reducing the risk of future osteoporosis.</p><p>Endometrial and ovarian cancer risk reduction. Use of oral</p><p>contraceptives has been associated with a reduced risk of</p><p>developing endometrial and ovarian cancer.</p><p>Overall, hormonal birth control can offer some relief for women</p><p>experiencing menopausal symptoms. As with any medication, it’s important</p><p>to consider potential side effects, health risks, and individual responses to</p><p>treatment. Hormonal birth control may not be suitable for all women,</p><p>particularly those with a history of blood clots, certain types of cancer, or</p><p>other health conditions. Side effects can include weight gain, breast</p><p>tenderness, and nausea. Mood swings and decreased libido are less</p><p>common.</p><p>In recent years, there has been growing attention and controversy</p><p>surrounding a potential link between birth control and mental health. This</p><p>debate was fueled by a few studies reporting associations between</p><p>hormonal contraceptives and an increased risk of depression. The largest</p><p>study so far analyzed data from over one million Danish women aged</p><p>fifteen to thirty-four, showing that those using hormonal contraception had</p><p>a higher chance of starting antidepressants compared to those who didn’t</p><p>use hormonal contraception. These results made the headlines, prompting</p><p>serious concerns. When we are looking at the data, however, it’s important</p><p>to note that the actual increase in the number of cases remained relatively</p><p>small. In fact, about two to three women from the first group (hormonal</p><p>contraception users) started using antidepressants every year as compared to</p><p>one to two women from the second group (nonusers). So that’s a difference</p><p>of only one or two women. Nonetheless, women considering hormonal</p><p>birth control should discuss their mental health history, especially a prior</p><p>history of depression, and any related concerns with their healthcare</p><p>provider in order to make informed decisions about their options.</p><p>Overall, hormonal contraception may be helpful as an alternative form of</p><p>hormone therapy with contraceptive benefits during perimenopause, often</p><p>providing a respite from vasomotor symptoms. If you are interested in this</p><p>option, below are some frequently asked questions:</p><p>Will taking contraception delay or hasten perimenopause or</p><p>the onset of menopause?</p><p>No, birth control neither delays nor precipitates menopause.</p><p>What it can do, though, is conceal the menstrual irregularities that</p><p>might have given you the first clues that you are nearing</p><p>menopause. Combination pills (pills with estrogen and</p><p>progesterone) cause a monthly withdrawal bleed that can appear the</p><p>same as a monthly period. Even after menopause, you may continue</p><p>to bleed similarly to how you would on your period. If instead you</p><p>are using a progestogen-only contraceptive, such as the</p><p>progestogen-only pill, implant, injection, or IUD, you might not</p><p>have any periods at all. This can make it hard to tell if you’ve</p><p>completed the transition to menopause. The best way to determine</p><p>if you are in menopause while taking contraceptives is to receive an</p><p>evaluation by an ob-gyn specialist.</p><p>Can HRT be used in place of contraception?</p><p>No, HRT is not a form of contraception.</p><p>Can you stop using contraception once perimenopausal or</p><p>postmenopausal?</p><p>While the likelihood of conceiving drops after age forty-five,</p><p>there is still a good chance. You can still ovulate (produce eggs) for</p><p>as long as you are having periods, even if they are irregular.</p><p>According to current guidelines, women under age fifty are advised</p><p>to keep using contraception for two years after the last menstrual</p><p>period to avoid pregnancy. Those over age fifty are advised to use</p><p>contraception for one year after their last period. Your doctor can</p><p>advise based on your personal situation and medical history.</p><p>Can birth control be taken together</p><p>with HRT?</p><p>Many birth control methods can be safely taken along with HRT.</p><p>Antidepressants</p><p>While hormonal therapies can help with a wide variety of physical and</p><p>brain symptoms of menopause, a well-informed conversation should also</p><p>include a discussion of the role of antidepressants. In the realm of</p><p>menopause management, antidepressants have garnered a somewhat</p><p>negative reputation, primarily because women experiencing menopausal</p><p>symptoms are often misdiagnosed with anxiety or depression.</p><p>Consequently, they may be prescribed antidepressants instead of receiving</p><p>targeted treatment for menopause. This misdiagnosis perpetuates the idea</p><p>that antidepressants are an inadequate or inappropriate solution. However,</p><p>when used correctly and under the guidance of a healthcare professional,</p><p>these meds can provide significant relief from menopausal symptoms such</p><p>as hot flashes and depression, while also improving the quality of life for</p><p>many women. Specific antidepressants are in fact recommended as a first-</p><p>line treatment for hot flashes in women who cannot take estrogen, such as</p><p>those with hormone-dependent cancer. Importantly, many studies have been</p><p>conducted in women with a history of breast cancer, indicating that these</p><p>medications can reduce hot flashes by 20 to 60 percent compared to</p><p>placebo.</p><p>It’s also important to note that antidepressants may be just as helpful as</p><p>HRT in specific circumstances, including treatment of severe depressive</p><p>symptoms during perimenopause, treatment of depression after menopause,</p><p>and treatment of major depression before or after menopause.</p><p>Antidepressants that have been tested for relief of menopausal symptoms</p><p>include selective serotonin reuptake inhibitors (SSRIs) and serotonin-</p><p>norepinephrine uptake inhibitors (SNRIs). The exact mechanism by which</p><p>SSRIs and SNRIs alleviate hot flashes is not fully understood, but it is</p><p>believed that their effects on serotonin and norepinephrine</p><p>neurotransmitters play a role in regulating the body’s temperature control.</p><p>Currently, the SSRI paroxetine (the brand name is Brisdelle) is approved by</p><p>the FDA for the treatment of moderate to severe menopausal hot flashes</p><p>and night sweats. Low-dose paroxetine can significantly reduce the</p><p>frequency and severity of hot flashes and night sweats, while also</p><p>improving sleep, without negative effects on libido or weight gain.</p><p>Other antidepressants—citalopram (Celexa), escitalopram (Lexapro),</p><p>venlafaxine (Effexor), and desvenlafaxine (Pristiq)—have also shown</p><p>efficacy in menopausal women. In clinical trials, desvenlafaxine was shown</p><p>to reduce hot flashes by 62 percent and to lessen their severity by 25</p><p>percent. Escitalopram reduced hot flash severity by about 50 percent. On</p><p>the other hand, common antidepressants such as fluoxetine (Prozac) and</p><p>sertraline (Zoloft) do not work as well for menopausal symptoms as the</p><p>other antidepressants listed.</p><p>It’s also worth noting that antidepressants can act quickly, usually</p><p>providing relief within a few weeks of use. However, the effectiveness of</p><p>these medications varies among individuals, and some patients might not</p><p>experience significant relief or may experience side effects. The most</p><p>common side effect is withdrawal symptoms. Additionally, some</p><p>antidepressants, such as paroxetine, can interfere with tamoxifen, a</p><p>common cancer drug, potentially reducing its effectiveness. Citalopram,</p><p>escitalopram, and venlafaxine are safer options in this case.</p><p>Fezolinetant</p><p>Fezolinetant (marketed under the brand name Veozah) is a novel FDA-</p><p>approved nonhormonal drug specifically designed for treatment of</p><p>moderate to severe hot flashes. It is a type of medicine called a selective</p><p>neurokinin-3 (NK3) receptor antagonist. This is because fezolinetant</p><p>functions by targeting a protein known as neurokinin B that binds to NK3</p><p>receptors in the hypothalamus—the brain region that regulates body</p><p>temperature. By blocking the attachment of the protein to the receptors, the</p><p>drug alleviates the severity and frequency of hot flashes. Fezolinetant could</p><p>be a game changer for women who are ineligible for HRT or those</p><p>interested in alternative treatments. Its FDA approval also signifies an</p><p>increasing acknowledgment of menopausal symptoms and the importance</p><p>of addressing them, paving the way for more nonhormonal options to</p><p>emerge in the near future.</p><p>From a practical standpoint, Fezolinetant is an oral pill taken once a day.</p><p>Its safety and efficacy were evaluated in randomized, placebo-controlled</p><p>Phase 3 clinical trials involving over two thousand women ages forty to</p><p>sixty-five experiencing seven or more hot flashes per day. The results</p><p>demonstrated a significant reduction in the frequency of moderate to severe</p><p>hot flashes, by 48 percent for women taking a higher dose of the drug and</p><p>by 36 percent in those on a lower dose, compared to 33 percent in the</p><p>placebo group. However, as the trials lasted only one year, the long-term</p><p>effects of this medication remain unknown. Fezolinetant has some side</p><p>effects, including GI issues and elevated hepatic transaminases, which are a</p><p>marker of potential liver damage. Therefore, it is recommended to undergo</p><p>bloodwork before and during treatment to monitor liver function.</p><p>Gabapentin</p><p>Gabapentin (brand name Neurontin) is an FDA-approved drug for epilepsy</p><p>that, in multiple trials, improved the frequency and severity of hot flashes</p><p>and, perhaps more so, night sweats. Some feel that gabapentin may be a</p><p>good choice for women experiencing menopause-related sleep disturbances</p><p>because it promotes sleepiness. It may be taken as a single bedtime dose (if</p><p>hot flashes are most bothersome at night) or during the daytime. Gabapentin</p><p>can be taken with tamoxifen and aromatase inhibitors. Side effects may</p><p>include dizziness, unsteadiness, and drowsiness, which typically improve</p><p>after two weeks of use, and withdrawal symptoms.</p><p>Pregabalin</p><p>A close relative of gabapentin, pregabalin (Lyrica) is commonly used for</p><p>seizures, pain, and fibromyalgia. It may help to relieve hot flashes, though it</p><p>is less well studied than gabapentin in this regard. However, it can help</p><p>reduce anxiety in menopause and can be taken with tamoxifen and</p><p>aromatase inhibitors. Its side effects are similar to gabapentin but less</p><p>noticeable.</p><p>Clonidine</p><p>Clonidine (Catapres) is a medication that lowers blood pressure and may be</p><p>used to prevent migraines. It can be given to reduce menopausal hot flashes,</p><p>though it seems less effective than antidepressants or gabapentin. It is also</p><p>used less frequently than other medications because of possible adverse</p><p>effects, including low blood pressure, headaches, dizziness, and sedative</p><p>effects. Current guidelines do not recommend that clonidine be given before</p><p>trying other options.</p><p>Oxybutynin</p><p>Oxybutynin is used to treat overactive bladder and urinary incontinence, but</p><p>it can also help with hot flashes. It can be taken with cancer treatments such</p><p>as tamoxifen and aromatase inhibitors. The most bothersome side effect is</p><p>dry mouth.</p><p>11</p><p>Cancer Therapies and “Chemo</p><p>Brain”</p><p>WORRIES ABOUT ESTROGEN AND BREAST CANCER</p><p>Cancer is a word that strikes fear into everybody’s heart and can produce a</p><p>deep sense of powerlessness. Few women are immune to worries about</p><p>breast cancer in particular, the nightmare illness in nearly all calculations</p><p>around hormone treatments. Most of us know someone who has had it or</p><p>who is fighting it at present. If we haven’t been touched by it directly, we</p><p>are still well aware of the risk, in part because of other women’s stories.</p><p>Every year, 1.4 million women worldwide are diagnosed with breast</p><p>cancer, which still results in over 400,000 deaths annually. While breast</p><p>cancer is a multifactorial disease, 60 to 80 percent of all cases are related to</p><p>sex hormones. Many reproductive tumors contain so-called estrogen</p><p>receptor positive cells, which are equipped with their own brand of</p><p>receptors that attach to estrogen. As they latch on to the estrogen flowing in</p><p>the bloodstream, they grow and get stronger. As a result, treatment for these</p><p>types of cancer is</p><p>aimed at blocking or suppressing estrogen to stop the</p><p>cancer and then to prevent it from reoccurring. This can be done in</p><p>combination with chemotherapy and sometimes surgery to remove breast</p><p>tissue (mastectomy).</p><p>Two of the most frequently prescribed hormonal treatments for breast</p><p>cancer, known as endocrine therapy in medical circles, are:</p><p>Selective estrogen receptor modulators (SERMs), aka estrogen</p><p>blockers. As the name implies, the job of estrogen blockers is to</p><p>block estrogen receptors in cancer cells. They work like a broken</p><p>key in a lock. By sticking to the receptors (the lock), they prevent</p><p>the normal key (estrogen) from fitting anymore, thereby stopping</p><p>the tumor in its tracks. The most commonly used drug is tamoxifen.</p><p>Aromatase inhibitors. These drugs stop estrogen production in the</p><p>entire body by obstructing the action of aromatase, the enzyme</p><p>needed to produce estrogen. Aromatase inhibitors can be steroidal,</p><p>like exemestane, and nonsteroidal, like anastrozole and letrozole.</p><p>Without going into too much detail, this distinction highlights the</p><p>different way these drugs turn off the aromatase enzyme.</p><p>These therapies can quite literally be lifesavers, often eradicating the</p><p>disease completely or at the very least extending the life of millions of</p><p>women. However, they affect estrogen action and production not only in</p><p>breast tissue but in other parts of the body, too. Case in point: They can</p><p>affect the ovaries, stopping ovulation and menstruation. This can be a</p><p>temporary side effect or a permanent one—in the latter case, provoking</p><p>medical menopause, no matter a woman’s age. These drugs can also spur</p><p>the telltale symptoms of menopause. For example, about 40 percent of</p><p>women taking estrogen-blocking tamoxifen experience hot flashes. Other</p><p>brain symptoms are also common, including brain fog and mood and</p><p>memory changes, which many refer to as “chemo brain.” These symptoms</p><p>can be so severe as to make cancer patients wonder if they are experiencing</p><p>an early onset of dementia. As you may have noticed, worry over the</p><p>perception of one’s diminished cognitive capacity to the point of fearing</p><p>dementia is a common theme in this book, one that we seriously need to</p><p>address.</p><p>In 2018, I wrote an op-ed in The New York Times about the connection</p><p>between menopause and Alzheimer’s disease. I did so with the intention of</p><p>raising awareness about this pivotal life transition as an important yet</p><p>largely overlooked element in women’s brain health. I expected that it</p><p>might stir up a number of strong reactions in various communities, but I</p><p>wasn’t expecting all the emails I received from breast cancer patients in</p><p>particular. Because I highlighted the connection between a lack of estrogen</p><p>and a possibly increased risk of Alzheimer’s, many reach out still today, out</p><p>of concern that their cancer medicines might be at unfortunate odds with the</p><p>health of their brains.</p><p>Back when I was writing the op-ed, there wasn’t quite enough data to</p><p>answer these urgent questions. Thankfully, the past few years have seen an</p><p>increasing awareness of the importance of estrogen for brain health—and it</p><p>certainly helped that more and more women have been demanding accurate</p><p>information about this important link and all its possible implications. All</p><p>of this has spurred not only renewed interest in the topic but also more</p><p>research focused on evaluating the impact of endocrine therapy on</p><p>cognitive health in cancer patients, as well as fairly heated discussions on</p><p>the possible role of HRT. It is this updated information that I am going to</p><p>share in this chapter.</p><p>OVARIAN CANCER</p><p>Before we begin, it’s important to talk about ovarian cancer, too. Ovarian</p><p>cancer often goes hand in hand with breast cancer, in part due to the often</p><p>undiscussed hormonal connection between our breasts and our ovaries. As</p><p>with breast cancer, ovarian cancer becomes more common as women get</p><p>older, the risk increasing after menopause. Our breasts and ovaries are also</p><p>connected through a genetic component, as evidenced by the fact that some</p><p>genetic mutations can increase the risk of both cancers, and the presence of</p><p>one cancer can elevate the risk of the other.</p><p>Typically, treatment for ovarian cancer also involves a combination of</p><p>chemotherapy and surgery, with oophorectomy being a first-line treatment.</p><p>Oophorectomy can be unilateral (only one ovary is removed) or bilateral</p><p>(both ovaries are removed). When the ovaries are removed along with the</p><p>fallopian tubes, the procedure is called a bilateral salpingo-oophorectomy</p><p>(BSO). BSO is of established benefit when ovarian cancer is found or</p><p>suspected. It is also recommended in patients with significant family history</p><p>of ovarian cancer or proven genetic predisposition, such as specific BRCA</p><p>(BReast CAncer) gene mutations, and those with medical conditions known</p><p>as Lynch syndrome and Peutz-Jeghers syndrome. However, there is</p><p>accumulating evidence that ovarian cancer may actually originate in the</p><p>fallopian tubes. Therefore, removing the tubes without the ovaries may be a</p><p>viable strategy to reduce that risk for some individuals undergoing</p><p>preventative treatment.</p><p>A downside of the BSO procedure performed before menopause is that it</p><p>results in surgical menopause, which in combination with chemotherapy</p><p>can make for an especially complex mind-body experience. This is</p><p>important to be aware of, as patients are not always presented with a clear</p><p>picture of what the long-term effects of these treatments may involve or of</p><p>the courses of action available to deal with the symptoms that may occur.</p><p>CHEMO BRAIN IS REAL</p><p>Many cancer patients worry about or downright suffer from what they</p><p>describe as mental cloudiness before, during, and after their cancer</p><p>treatment. Sadly, chemo brain is another textbook example of how women’s</p><p>concerns around their cognitive and mental health have been dismissed by</p><p>the medical field. Despite what cancer patients have been saying for</p><p>decades, until very recently, physicians chalked up these symptoms to</p><p>fatigue, depression, anxiety, and the stress of the cancer and treatment. The</p><p>patients’ belief that their symptoms were not due to being depressed,</p><p>anxious, or fatigued was not taken seriously enough, either because some</p><p>providers didn’t believe that cancer treatment may have negative effects on</p><p>the brain or because they lacked training to address these specific issues.</p><p>Regrettably, many patients continue to encounter the same barriers even in</p><p>the present day.</p><p>If you or anyone you know has encountered these issues, I am here to</p><p>assure you that chemo brain is not just your imagination. Chemo brain is</p><p>real. It is a legitimate, diagnosable condition that’s receiving increasing</p><p>validation and attention.</p><p>A main reason for greater acceptance of chemo brain as an actual</p><p>medical condition is better imaging of the brain. Some imaging studies have</p><p>found that chemo brain is associated with measurable changes to the brain’s</p><p>white matter, particularly to the fiber tracks connecting the hippocampus</p><p>and prefrontal cortex. As you know, these areas of the brain are involved in</p><p>memory and higher-level cognitive functioning. Other parts of the brain</p><p>involved in cognitive functions can also undergo changes in both</p><p>connectivity and activity following chemotherapy. These observations have</p><p>significantly contributed to a shift in the general mindset by underscoring</p><p>the direct impact of certain cancer therapies on the structure and</p><p>functionality of the brain, thereby providing support to the reports of</p><p>patients experiencing chemo brain.</p><p>Today, in the medical field, chemo brain is referred to as cancer-</p><p>treatment-related cognitive impairment, cancer-related cognitive change, or</p><p>post-chemotherapy cognitive impairment. I am not a fan of the word</p><p>impairment in these phrases for reasons we’ll discuss in a moment, but</p><p>nonetheless, chemo brain is a symptom reported by as many as 75 percent</p><p>of cancer patients. It is often described as difficulty processing information</p><p>and feeling as if you can’t think as quickly and as clearly as you did</p><p>before</p><p>you had cancer or started treatment. Everyday tasks require more</p><p>concentration and take more time and effort to take care of. As you may</p><p>have noticed, this is not too dissimilar from the brain fog experienced by</p><p>women undergoing menopause. Here are some examples of what patients</p><p>with chemo brain may experience:</p><p>Problems with short-term memory; forgetting details like names,</p><p>dates, and sometimes events; forgetting things that you usually have</p><p>no trouble remembering (memory lapses); confusing dates and</p><p>appointments</p><p>Difficulty concentrating; reduced focus; a shorter attention span</p><p>Feeling mentally slower than usual; taking longer to finish things,</p><p>feeling disorganized, with slower thinking and processing</p><p>Trouble learning new things</p><p>Trouble multitasking</p><p>Fumbling for the right word or phrase, like being unable to find the</p><p>right words to finish a sentence</p><p>Having trouble following a conversation or initiating one</p><p>Having trouble finding your way around</p><p>Feeling sluggish or tired or not having energy</p><p>Feeling clumsy, as if something’s wrong with your motor skills</p><p>What causes chemo brain? Despite its name, chemo brain may happen</p><p>for different reasons. It can be caused by the cancer itself, by chemotherapy</p><p>treatment, or by secondary medical conditions such as anemia. While it is</p><p>most commonly connected with chemotherapy, other treatments, such as</p><p>additional endocrine therapy, radiation, and surgery, may be associated with</p><p>it, too—not to mention the inflammation that can result from these</p><p>treatments. In other words, cancer patients can experience chemo brain</p><p>even though they haven’t had chemotherapy.</p><p>Anyone can develop cognitive problems before, during, or after receiving</p><p>treatment. No matter the duration, chemo brain can severely disrupt quality</p><p>of life and affect performance both at work and at home. Usually, chemo</p><p>brain is a short-term issue, and cognitive function usually improves after the</p><p>end of therapy. Most of the time, the foggy sensation fades away six to</p><p>twelve months after the cancer is successfully treated. However, in some</p><p>cases, the symptoms may last for months, sometimes years, after the end of</p><p>treatment. These long-term cognitive difficulties need acknowledging and</p><p>addressing.</p><p>As always, nobody is suggesting that patients decline or avoid treatment.</p><p>Far from it. I am sharing this information because it’s important to know</p><p>what these procedures involve, from a whole-body and brain perspective.</p><p>The goal is not to endanger anybody’s life by getting them to go off cancer</p><p>medications, but to draw attention to these largely understudied issues.</p><p>Is Chemo Brain a Sign of Dementia?</p><p>The fact that estrogen blockers and aromatase inhibitors suppress estrogen</p><p>function has spurred concerns around a possible risk of dementia. The</p><p>tricky thing here is that endocrine (hormonal) therapy can be done with or</p><p>without chemotherapy, and the effects of these two treatments are difficult</p><p>to tell apart. Nonetheless, several studies have shown that chemotherapy is</p><p>the major culprit behind the brain fog and memory lapses, whereas</p><p>endocrine therapy has more variable effects, which depend on several</p><p>factors, especially the patient’s age and type of treatment. For example,</p><p>tamoxifen—the most common estrogen blocker typically given to women</p><p>who are not yet in menopause—can have negative effects on memory and</p><p>speech production. It goes without saying that if a woman is receiving both</p><p>chemotherapy and tamoxifen, her brain fog may be worse than with either</p><p>type of treatment by itself. On the other hand, aromatase inhibitors don’t</p><p>seem to have clear negative effects on cognitive performance, at least in</p><p>postmenopausal women.</p><p>Specifically for Alzheimer’s disease, although research on this topic is</p><p>scant, some studies have shown that patients treated with tamoxifen don’t</p><p>have an increased risk of dementia as compared to patients on other</p><p>treatments. How can this be? While tamoxifen blocks estrogen receptors in</p><p>breast tissue, it has neutral or positive effects in other parts of the body. It is</p><p>possible, then, that after a temporary negative impact on cognitive</p><p>performance, the drug may have mild or no long-term effects overall. As for</p><p>aromatase inhibitors, there are some differences between steroidal and</p><p>nonsteroidal formulations. Exemestane, a steroidal aromatase inhibitor, has</p><p>been linked with a possibly lower risk of dementia than the nonsteroidal</p><p>drugs anastrozole and letrozole. While more research is sorely needed to</p><p>confirm these findings, this information can already help support</p><p>conversations with medical providers about both the cancer and a patient’s</p><p>brain health, as current guidelines permit the choice between different</p><p>treatment regimens. Personally, I’d also argue for a more integrative</p><p>approach to cancer care that includes brain specialists besides oncologists</p><p>and surgeons. Whenever there is a real concern about cognitive impairment</p><p>or dementia, or when patients continue to struggle with significant cognitive</p><p>concerns and functional reintegration six to twelve months after the end of</p><p>treatment, a proper neurological evaluation with brain imaging and</p><p>neuropsychological testing can make all the difference.</p><p>Just as important, I want to be clear that chemo brain and perceived</p><p>declines in cognitive power do not necessarily constitute cognitive</p><p>impairment, no matter what words your doctor chooses to use. While it is</p><p>true that many cancer patients experience a decline in cognitive</p><p>performance during or after treatment, these changes are hardly ever severe</p><p>enough to fall in the “impaired” range of cognition—let alone meet an</p><p>actual diagnosis of impaired cognitive status or dementia. Unfortunately</p><p>many providers fail to recognize this important distinction and use the term</p><p>impairment to describe any decline in cognitive performance, whether</p><p>measurable or perceived. We need to be more mindful of our choice of</p><p>words. Telling patients they are cognitively impaired when they are not can</p><p>have negative effects on their quality of life, as well as on their stress and</p><p>anxiety levels, not to mention their self-esteem. In the clearest possible</p><p>terms, suffering from chemo brain does not mean one is developing</p><p>dementia. As challenging and frightening as these symptoms can be, our</p><p>powerful brains have the ability to push through and recover. In cases where</p><p>the recovery seems challenging, seeking guidance from a brain expert can</p><p>provide valuable support and insights. If you have genuine concerns about</p><p>dementia, particularly if the symptoms of chemo brain persist or if you have</p><p>a family history of dementia, I recommend consulting with a neurologist or</p><p>gerontologist. By conducting targeted assessments, including blood work,</p><p>cognitive evaluations and specific brain scans, these specialists can provide</p><p>guidance regarding the best course of action.</p><p>Treating Chemo Brain</p><p>If you are experiencing chemo brain and the symptoms are causing trouble</p><p>in your daily life, ask your doctor if you might be helped by a specialist</p><p>such as a psychologist or psychotherapist, neuropsychologist, speech-</p><p>language pathologist, occupational therapist, or vocational therapist. These</p><p>professionals can test you and recommend ways to help you better handle</p><p>the problems you are experiencing. More generally, things that are proven</p><p>to help include:</p><p>Cognitive rehabilitation, involving activities to improve brain</p><p>function, such as learning how the brain works and ways to take in</p><p>new information and perform new tasks; doing some activities over</p><p>and over that become harder with time; and using tools to help stay</p><p>organized, such as planners or diaries.</p><p>Exercise, and more broadly, keeping physically active is good for</p><p>both your body and your brain, improving your mood, making you</p><p>feel more alert, and decreasing fatigue.</p><p>Meditation can increase your focus and awareness, while reducing</p><p>stress.</p><p>Rest and sleep can help your body and brain adjust and heal.</p><p>Avoiding alcohol, caffeine, and other stimulants that might change</p><p>your mental state and sleeping patterns.</p><p>Asking for help. Tell family members, friends, and your cancer care</p><p>team about any struggles. Their support and understanding can help</p><p>you relax and make it easier for you to focus on healing.</p><p>I HAD/HAVE BREAST AND/OR OVARIAN CANCER: CAN I TAKE HRT?</p><p>While the above practices are well accepted in the medical community, the</p><p>role of HRT in easing chemo brain and the long-term effects of induced</p><p>menopause in cancer patients are the subject of fierce debate. Most experts</p><p>feel that nonhormonal therapies should be the first approach in managing</p><p>menopausal symptoms in breast and ovarian cancer survivors. We talked</p><p>about nonhormonal medications in chapter 10 and will go over many</p><p>lifestyle options in part 4 of this book. When it comes to HRT, according to</p><p>professional societies, there is a lack of safety data supporting the use of</p><p>systemic (oral or transdermal) HRT in women who have had breast or</p><p>ovarian cancer. The risk of breast cancer recurrence with HRT is higher in</p><p>those with estrogen receptor positive cancer, but patients with estrogen</p><p>receptor negative breast cancer may also have an increased risk of the</p><p>cancer regrowing. Nonetheless, HRT may (the North American Menopause</p><p>Society adds “in exceptional cases”) be offered to patients with severe</p><p>menopausal symptoms if lifestyle modifications and nonhormonal options</p><p>are not effective. Additionally, hormone therapy “can be considered in</p><p>premenopausal women who undergo oophorectomy to completely remove</p><p>the cancer, based on considerations of the many benefits of estrogen therapy</p><p>for early menopause.” As a reminder, for the vast majority of women, low-</p><p>dose vaginal estradiol and DHEA (a hormone the body can convert into</p><p>estrogen and testosterone) are safe and effective at treating symptoms such</p><p>as vaginal dryness and genitourinary symptoms, without noticeable</p><p>increases in blood estrogen levels.</p><p>All this only further highlights the need to engage in comprehensive and</p><p>individualized discussions with your healthcare team so as to make</p><p>informed decisions that prioritize both your medical care and symptom</p><p>management, while also considering your personal risk tolerance. These</p><p>discussions will enable you to navigate the complexities of treatment</p><p>options and tailor them to your specific needs. I look forward to the next</p><p>generation of brain estrogens, or SERMs, becoming available, too. As we</p><p>discussed in the last chapter, SERMs can be engineered to selectively</p><p>supply estrogen to the brain while having neutral or even protective effects</p><p>on reproductive organs. Once this type of therapy is fully tested, there is</p><p>hope that it will be safe for all women, cancer patients included.</p><p>What If I Have a Family History of Breast or Ovarian Cancer?</p><p>In 2013, Angelina Jolie disclosed that she had a genetic mutation linked to a</p><p>strong risk of breast and ovarian cancer. The gene involved is BRCA-1. Its</p><p>mutations account for about 12 percent of all cases of breast cancers and for</p><p>another 10 to 15 percent of ovarian cancers. Although she did not have</p><p>cancer herself, Ms. Jolie decided to take preventative action and have her</p><p>breasts and ovaries removed. By doing so, she reduced her risk of both</p><p>cancers back to baseline levels. Ms. Jolie’s medical decision hit a nerve</p><p>with many women around the world. Her story was so impactful that it</p><p>undoubtedly led to a bevy of women calling their doctor’s office for</p><p>appointments for genetic counseling and breast screening—and questions</p><p>about what to do next.</p><p>If you’ve been there, you know. If you end up having your ovaries</p><p>removed, prompting early menopause, would it be safe to take HRT? Would</p><p>the recommendation of starting HRT as soon as possible after</p><p>oophorectomy apply to those with genetic mutations, or a family history of</p><p>breast cancer, or both?</p><p>HRT is indeed an option. Several studies indicate that hormone therapy is</p><p>viable for women who have genetic mutations or a family history of breast</p><p>cancer, but do not personally have the cancer. The same applies to mutation</p><p>carriers who opt for preventative surgery. So if you or someone you know is</p><p>in this situation and exploring potential options, it may be helpful to know</p><p>that HRT is on the table. Nonhormonal and lifestyle modifications should</p><p>be given equal consideration as they, too, play a significant role in</p><p>managing menopausal symptoms and supporting brain health. Ultimately,</p><p>the choice should be based on a comprehensive assessment of individual</p><p>circumstances and a shared decision-making process between each patient</p><p>and their healthcare providers.</p><p>MOVING BEYOND FEAR, TOGETHER</p><p>In my line of work, I am often reminded of how blessed I am to have not</p><p>only my health but also medical insurance and access to hospitals—not to</p><p>mention an education that helps me ask the right questions, sort through</p><p>difficult and often unclear information, and make informed decisions for</p><p>myself and my family.</p><p>I am here today, determined to put my privilege to good use for all</p><p>women around me. I am powerfully aware that somewhere else in the</p><p>world, perhaps just in the room next door, there’s a woman just like me,</p><p>with similar abilities and love for her family, who is waiting to find out if</p><p>she has cancer or needs surgery or she’s past treatment. She might be</p><p>worrying about being able to afford the visit or getting laid off for missing</p><p>work—or wondering if she’ll live long enough to see her kids grow.</p><p>Here in the United States, one in every eight women will develop breast</p><p>cancer in her lifetime. One in every nine will have an oophorectomy, many</p><p>due to cancer. One in every four will undergo induced menopause.</p><p>I stand strong in my determination that women who undergo any of these</p><p>realities are true warriors. They have a different approach to life, a different</p><p>look in their eye. They’ve confronted their own humanity in such a</p><p>profound way. They’ve stood up to danger and stigma and fear and all the</p><p>craziness of the medical establishment, which offers so little support to</p><p>menopausal women in general and to cancer survivors in particular. Many</p><p>of you may have already had this dreaded disease and will have wisdom to</p><p>share with us. On my end, I will do the best I can with my time, my</p><p>knowledge, and my voice to support and validate all women’s stories and</p><p>experiences and to make sure no voice gets subsumed in the noise of a</p><p>communal narrative that doesn’t reflect any of these realities. To this aim, I</p><p>launched an entire clinical research program dedicated to women’s health,</p><p>and I’m hoping this book enables more women to become aware of these</p><p>challenges and learn about possible solutions. Many others will hopefully</p><p>feel renewed compassion, if not a sense of duty and responsibility toward</p><p>those who are less fortunate and in need of help.</p><p>The ultimate goal, of course, is better solutions and better care for all. So</p><p>far, we have reviewed the risks and benefits of hormonal therapies for</p><p>cancer, the dos and don’ts of HRT, and the realistic alternatives provided by</p><p>nonhormonal medications. Additionally, in part 4, we’ll go over several</p><p>options cancer survivors have to safeguard their mind-body health as they</p><p>progress through their healing journey. These options do not involve taking</p><p>hormones or medications—they involve optimizing your lifestyle and</p><p>environment in ways that are conducive to brain health. For a quick</p><p>preview, lifestyle and behavioral techniques that are proven to help include</p><p>dietary management with appropriate supplements and specific exercise</p><p>regimens, as well as cognitive behavioral therapy, hypnosis, and relaxation</p><p>techniques. Remember, there is power in your everyday choices. This is an</p><p>important concept and one I hope you, too, will take to heart.</p><p>12</p><p>Gender-Affirming Therapy</p><p>SEX AND GENDER</p><p>In previous chapters, we have used the term women to discuss individuals</p><p>born with two X chromosomes and reproductive characteristics such as</p><p>breasts and ovaries, commonly known as cisgender women. This</p><p>combination has long been the biological definition of the female sex.</p><p>While the binary notion of</p><p>female or male, XX or XY, is deeply ingrained</p><p>in our society, the understanding of gender has evolved over time. In</p><p>medical science, we acknowledge that possessing a female reproductive</p><p>system does not dictate one’s gender identity. Some individuals do not</p><p>identify with the sex they were assigned at birth, rather expressing gender</p><p>on a spectrum, leading to the expansion of the LGBTQ community into the</p><p>LGBTQIA+ community (lesbian, gay, bisexual, transgender, queer or</p><p>questioning, intersex, asexual) in recent decades.</p><p>Transgender individuals, who represent around 0.5 percent of the U.S.</p><p>population, and intersex individuals, who account for approximately 2</p><p>percent, often face significant challenges in accessing appropriate</p><p>healthcare. Many medical providers lack training in transgender care in</p><p>particular, leaving up to half of all transgender individuals in the position of</p><p>having to inform their providers about their specific needs. Now add</p><p>hormones to the mix, and the picture becomes even more complex.</p><p>Accessible providers who specialize in gender-affirming therapies, which</p><p>may include hormonal and surgical treatments, generally do so with regard</p><p>to the patient’s body. Few are prepared to manage their patients’ cognitive</p><p>and mental well-being, too.</p><p>In our exploration of hormones’ effects on brain health, we will now</p><p>consider the experiences of transgender individuals who undergo hormonal</p><p>transitions during their gender-affirming therapy. This chapter discusses</p><p>transgender men in particular, who were assigned the female sex at birth but</p><p>who have transitioned to a male or masculine gender and may unknowingly</p><p>be experiencing brain changes related to both the treatment and to hormonal</p><p>changes due to, or not unlike, menopause. These brain-body changes are</p><p>much less researched and understood than hormonal transitions occurring in</p><p>cisgender women, making reliable information on the topic especially</p><p>challenging to find. We will also talk about transgender women, who were</p><p>assigned the male sex at birth and have transitioned to a female or feminine</p><p>gender, as they, too, may encounter similar challenges.</p><p>While I am not a psychologist or sociologist and must defer to other</p><p>professionals regarding the emotional and social aspects of gender</p><p>transition, I am committed to understanding how the hormonal changes that</p><p>may occur can impact an individual’s health and cognitive well-being.</p><p>Beyond my desire to make sure that this book is inclusive, another reason to</p><p>discuss how gender-affirming therapies impact the brain is that the</p><p>treatment of choice for transgender men often involves the use of</p><p>testosterone paired with estrogen-suppressing medications, which may</p><p>provoke either menopause itself or some of its symptoms. A better</p><p>understanding of the effect of these treatments will not only support further</p><p>progress in transgender care but also contribute to a more comprehensive</p><p>understanding of the diverse experiences of all people undergoing this</p><p>hormonal milestone.</p><p>GENDER IDENTITY: A PRIMER</p><p>Some may feel nonplussed about what transgender identity is and isn’t.</p><p>Others may confuse it with homosexuality. Here’s a good place to start:</p><p>Sexuality is about to whom you’re attracted. Gender identity is about who</p><p>you feel you are gender-wise. One’s gender identity can be separate from</p><p>one’s sexual preference.</p><p>Let’s go a little deeper. Cisgender women identify with the sex assigned</p><p>to them at birth. They were born with a reproductive system assigned</p><p>female and are at ease with their given genitalia and associated gender</p><p>identity. Ditto for cisgender men who were born with genitalia assigned</p><p>male and associate with that gender identity. Transgender individuals, on</p><p>the other hand, identify with the gender opposite their assigned sex. In</p><p>medical textbooks, the incongruence between one’s sense of gender and</p><p>one’s sex assigned at birth or social presentation is called gender dysphoria.</p><p>Gender dysphoria is a broader concept than just physical attributes. Trans</p><p>people can have body dysphoria and/or social dysphoria. One or the other</p><p>may present more strongly. Generally, the discomfort of being in a body</p><p>that does not feel like your own or that doesn’t match your identity can</p><p>cause considerable psychological suffering, increasing the risk of stress,</p><p>anxiety, and depression in turn.</p><p>Gender-Affirming Therapy</p><p>People who are transgender may pursue multiple domains of gender</p><p>affirmation, including social affirmation (e.g., changing one’s name and</p><p>pronouns), legal affirmation (e.g., changing gender markers on one’s</p><p>government-issued documents), medical affirmation (e.g., pubertal</p><p>suppression or gender-affirming hormones), and/or surgical affirmation</p><p>(e.g., vaginoplasty, facial surgery, breast augmentation, masculine chest</p><p>reconstruction, etc.). Of note, not all people who are transgender will desire</p><p>all domains of gender affirmation, as these are highly personal and</p><p>individual decisions.</p><p>Herein, I’ll focus on medical gender-affirming therapy (GAT), or cross-</p><p>sex therapy, which transgender and gender nonbinary individuals are</p><p>increasingly using to intercept their transition to puberty, or to match their</p><p>gender identity post-puberty. Medical GAT therefore includes a transition,</p><p>with hormones or surgery in some cases. GAT is generally used to reduce</p><p>the bodily characteristics of a person’s natal sex while inducing those of the</p><p>gender they identify with. Hormonal treatment is the more commonly used</p><p>route. Fewer transgender people elect to have surgery, whether because of</p><p>social, medical, or financial considerations, or just personal preference.</p><p>These complementary procedures and assistance are associated with</p><p>improved quality of life and mental health for many transgender</p><p>individuals.</p><p>There are two main types of GAT, depending on which gender one is</p><p>transitioning to:</p><p>▷ MASCULINIZING HORMONE THERAPY (OR TRANSMASCULINE, FEMALE-TO-</p><p>MALE HORMONE THERAPY)</p><p>Masculinizing hormone therapy is the GAT predominantly used by</p><p>transgender men as well as other transmasculine and intersex individuals.</p><p>The purpose is to change the secondary sexual characteristics from</p><p>feminine or androgynous to masculine, transforming the body into one</p><p>more congruent with a male gender identity. Masculinizing therapy</p><p>typically prompts voice deepening and the development of a masculine</p><p>pattern of hair, fat, and muscle distribution. If started before puberty, GAT</p><p>can prevent some breast and vulva development. If started after puberty,</p><p>GAT cannot undo breast and vulva development, which may be addressed</p><p>by surgery and other treatments.</p><p>The mainstay of masculinizing therapy is testosterone. Several</p><p>formulations are available, including intramuscular injections, transdermal</p><p>patches, gels, pellets, and pills. Anti-estrogen therapies are also used to</p><p>reduce the body’s production of estrogen and progesterone. Some of these</p><p>medicines are called gonadotropin-releasing hormone (GnRH) antagonists.</p><p>The term antagonists refers to the fact that these drugs work against the</p><p>release of LH and FSH hormones. This in turn stops the production of</p><p>estrogen and progesterone in the ovaries. Some estrogen blockers and</p><p>aromatase inhibitors, like the drugs used for cancer treatment discussed in</p><p>the last chapter, can also be used. Additionally, some transgender men</p><p>choose surgeries to remove the breasts, uterus, and/or ovaries, and may</p><p>elect to undergo reconstructive surgeries afterward. These changes</p><p>additionally alter the hormonal milieu of transgender men.</p><p>In terms of timeline, increased body hair growth, scalp hair loss, and an</p><p>increase in muscle mass and strength usually occur within a year of starting</p><p>masculinizing therapy. The menstrual cycle stops after just two to six</p><p>months of treatment. The one thing that this treatment doesn’t necessarily</p><p>stop is ovulation. This exception means that transgender men can become</p><p>pregnant (unless contraception is used) and that they will go through</p><p>menopause when the time comes. As we find new ways to honor the</p><p>fluidity of gender, we bump</p><p>into the fact that our physiological sex may not</p><p>be as flexible as our gender identity. So to be clear, if a person is born with</p><p>ovaries and has had a menstrual cycle at some point in their lives, they will</p><p>inevitably go through menopause.</p><p>So here we are looking at a double transition—one for gender affirmation</p><p>and the other for menopause. These transitions can intertwine, potentially</p><p>complicating each other. For transgender men, menopause can happen</p><p>spontaneously, over time, or as a result of surgery. Transgender men who</p><p>undergo an oophorectomy (the surgical removal of the ovaries, possibly</p><p>along with the uterus) will develop menopause soon after surgery, incurring</p><p>the same risks as a cisgender woman undergoing induced menopause. As</p><p>discussed throughout the book, oophorectomies before menopause may</p><p>increase a person’s risk of developing heart disease and osteoporosis, as</p><p>well as anxiety, depression, and even cognitive impairment in older age.</p><p>Unfortunately, transgender men are seldom offered adequate preparation for</p><p>what menopause involves, whether spontaneous or induced. It is my hope</p><p>this book will help provide clarity on what to expect and how to mitigate</p><p>possible symptoms and side effects.</p><p>▷ FEMINIZING HORMONE THERAPY (TRANSFEMININE OR MALE-TO-FEMALE</p><p>HORMONE THERAPY)</p><p>Feminizing hormone therapy is the GAT predominantly used by transgender</p><p>women as well as other transfeminine and intersex people. In this case,</p><p>GAT is used to feminize their bodies. Treatment typically involves oral,</p><p>transdermal, or injectable estrogen preparations, often in conjunction with</p><p>GnRH analogs. These GnRH drugs stimulate estrogen and progesterone</p><p>production (as opposed to the GnRH antagonists mentioned above). Anti-</p><p>androgen medicines can also be used, in this case to suppress testosterone.</p><p>Does GAT Change the Brain?</p><p>Now that we’ve reviewed the main types of GAT, let’s return to my</p><p>wheelhouse: brain health. Do masculinizing and feminizing treatments have</p><p>any notable effects on the brain?</p><p>It is important to note that introducing external hormones while</p><p>dramatically reducing the body’s own hormonal production impacts the</p><p>entire body, the brain included. While the effects of hormones on</p><p>appearance and sexual characteristics are self-evident, we’ve yet to compile</p><p>adequate clinical research on how GAT impacts the brain. Research on</p><p>transgender individuals is still in its infancy, and the majority of whatever</p><p>few studies have been carried out focus on transgender women. There are</p><p>hardly any brain studies of transgender men, highlighting, once again, the</p><p>healthcare stigma and marginalization discussed throughout this book.</p><p>Another issue is that most studies so far have limited themselves to young</p><p>transgender individuals in their early twenties and thirties, if not younger.</p><p>Nonetheless, let’s take a look at what we have to work with so far.</p><p>As discussed at the beginning of this book, research on cisgender</p><p>individuals has shown that men’s and women’s brains have some</p><p>differences. Those most often cited are that men’s brains tend to be bigger</p><p>overall and women’s brains tend to be more interconnected. These facts are</p><p>interesting to ponder, as we review the impact of GAT on the brain.</p><p>Some studies have used MRI scans to look at the brain before and after</p><p>GAT treatment in transgender individuals, mostly transgender women. The</p><p>scans allowed the researchers to take a peek at the brain’s gray matter to</p><p>monitor if it was thicker or thinner after feminizing GAT, simultaneously</p><p>measuring any changes in connectivity between brain regions near and far.</p><p>The results are intriguing. After six months to a year of treatment with anti-</p><p>testosterone medicines, some specific brain regions of transgender women</p><p>had indeed grown smaller, whereas their connectivity had increased. In</p><p>other words, GAT prompted the brains of transgender women to exhibit</p><p>some of the structural characteristics of a cisgender female brain, being</p><p>typically smaller and more interconnected relative to those of cisgender</p><p>men. While there are fewer studies of this transition, this mirror crossover is</p><p>seen in transgender men, too. In this case, treatment with testosterone and</p><p>anti-estrogen medicines had the exact opposite effect on the brain,</p><p>increasing its volume overall, as well as in several regions typically larger</p><p>in cisgender men. Overall, GAT appears to align a person’s brain with those</p><p>characteristics comparable to the gender with which the person identifies, at</p><p>least to some degree. These results also suggest that GAT changes the brain</p><p>as surely as it does the body, perhaps in ways that may help relieve the</p><p>feeling of incongruence between one’s body and gender identity. However,</p><p>what may come as a surprise is that these changes may simultaneously</p><p>impact a person’s mood, energy levels, sleep patterns, cognitive</p><p>performance, and even long-term health, as discussed below.</p><p>How Do These Changes Impact One’s Health?</p><p>From a clinical perspective, besides the desired changes in bodily</p><p>appearance, GAT has some additional pros and cons. For example,</p><p>transgender men receiving testosterone therapy tend to report increased</p><p>energy, focus, appetite, and libido, along with a decreased need for sleep.</p><p>That’s the good news. The not-so-good news is that treatment may trigger</p><p>hot flashes, brain fog, depressive episodes, and other brain symptoms of</p><p>menopause. These changes may be more severe when the ovaries are</p><p>removed, which can occur as early as puberty if that’s when the surgery</p><p>occurs. Masculinizing GAT can also cause vaginal atrophy and dryness. In</p><p>this case, topical estrogen creams and lubricants can help (see chapter 9). In</p><p>the long term, this type of treatment may increase the risk of osteoporosis</p><p>and polycystic ovary syndrome (PCOS), which, if left untreated, has been</p><p>linked to decreased fertility and a possible increased risk of endometrial</p><p>cancer. These risks are important to acknowledge and address, as are those</p><p>related to undergoing an oophorectomy before the natural age of</p><p>menopause.</p><p>Transgender women may experience somewhat opposite changes after</p><p>anti-testosterone and/or estrogen therapy, such as reduced libido and</p><p>alterations in mood, sleep, and temperature sensitivity. This is also not too</p><p>different from menopause brain. According to some studies looking at long-</p><p>term effects, transgender women on GAT may have a higher risk of heart</p><p>disease and breast cancer than cisgender men.</p><p>GAT’s Effects on Cognitive Performance</p><p>Given all that we’ve come to understand about the effects of hormonal</p><p>changes on brain health, one can’t help but wonder if GAT could also</p><p>impact cognitive functioning. For the time being, we need more</p><p>information, as research on the long-term risks and benefits of GAT is still</p><p>minimal, and the few existing studies on the topic are also limited to young</p><p>transgender individuals, mostly transgender women. Nonetheless, the most</p><p>extensive study so far, combining data from several hundred young adult</p><p>transgender men and women, indicates no clear negative effects in the short</p><p>term. Rather, transgender men on testosterone therapy showed somewhat</p><p>enhanced visuospatial performance, while transgender women on estrogen</p><p>therapy exhibited a slight improvement in verbal memory. If you recall</p><p>from previous chapters, while the jury’s still out as to whether cognitive</p><p>differences can be reliably found between the genders, these results align</p><p>with those cognitive strengths comparable to the gender with which the</p><p>person identifies (cisgender women tend to have better verbal memory than</p><p>cisgender men, while cisgender men may have better visuospatial abilities</p><p>than cisgender women).</p><p>That said, it is baffling that virtually nothing is known about GAT effects</p><p>among transgender people over thirty, transgender men in particular. We</p><p>have yet to collect enough reliable information on how GAT and</p><p>menopause combined could impact cognitive and mental health in groups</p><p>of people, let alone for each individual. This duo is a noteworthy one to</p><p>examine, especially given</p><p>the higher rates of anxiety and depression</p><p>experienced by many transgender individuals already before menopause.</p><p>While we develop the studies necessary to guide and protect transgender</p><p>people through their transitions with care and know-how, for now we await</p><p>additional data to assess GAT’s fuller impact on cognition.</p><p>This waiting game makes preventative care all the more essential. As we</p><p>wait for the data to roll in, my advice is the same for transgender</p><p>individuals as it is for everybody else. As we’ve come to understand just</p><p>how critical hormones are to a myriad of brain functions and how</p><p>menopause may impact those brain functions, we must take excellent care</p><p>as we pioneer the process. My best advice is to treat your brain as your best</p><p>friend and show it your utmost respect, at all ages and stages of life. This</p><p>book is here to ensure that you are prioritizing your brain and mental health</p><p>using scientifically validated techniques that are proven to work. As our</p><p>culture and medical field integrate the latest findings from the front lines,</p><p>it’s up to us to fortify our brain’s well-being using the tools discussed in</p><p>these pages.</p><p>PA RT 4</p><p>LIFESTYLE AND INTEGRATIVE</p><p>HEALTH</p><p>13</p><p>Exercise</p><p>THE POWER OF LIFESTYLE</p><p>So far we’ve discussed prescription medicines that can help alleviate the</p><p>symptoms of menopause and support you through this journey. However,</p><p>many women prefer to rely on natural remedies, diet, and exercise instead.</p><p>Fortunately, this is perfectly feasible, and a wide array of lifestyle changes</p><p>and self-care practices are available. Importantly, these techniques are just</p><p>as valuable if HRT or other medications are part of your plan.</p><p>When it comes to lifestyle, menopause is a great moment to select new</p><p>healthy habits and to keep consistent with positive current ones. In this</p><p>spirit, I want you to think of your brain as a muscle. You can incorporate</p><p>behaviors that strengthen the brain, just as you train your muscles. You can</p><p>exercise it, feed it properly, take care of it properly—and when you do, your</p><p>brain will perform much better for you, at any age. Things like eating a</p><p>nutritious diet, avoiding toxins, and keeping stress under control can really</p><p>make a difference, as do exercise, sleep, and a mindset fueled with facts,</p><p>not fiction. Your body and brain will take care of you if you take care of</p><p>them.</p><p>Harnessing this prescribed lifestyle’s power can influence how your brain</p><p>responds to menopause, making you feel better, lighter, and brighter on</p><p>your way. If you are having a hard time during the period leading up to</p><p>menopause, it’s helpful to remember that you have agency over your</p><p>lifestyle, environment, and beliefs. These factors can play a significant role</p><p>in shaping your experience of menopause. Just as hormonal changes can</p><p>affect your sleep, focus, and body composition, your daily habits can also</p><p>influence your hormone levels and the intensity of their effects on your</p><p>body.</p><p>I want to make clear that I am not here to download a to-do list to</p><p>“overcome” or “beat” menopause. Remember, menopause is not an enemy.</p><p>Above all, I am not interested in selling you on a program that will make</p><p>your brain impervious to menopause or magically propel you beyond it.</p><p>That’s just science fiction. The vetted lifestyle choices discussed ahead are</p><p>based on tried-and-true research. Tangible benefits are feasible with time,</p><p>consistency, and persistence. Let’s go!</p><p>EXERCISE FOR A HEALTHY MENOPAUSE</p><p>It’ll probably come as no surprise that most of us aren’t on the move nearly</p><p>as much as would be optimal, not even close! According to the U.S. Centers</p><p>for Disease Control and Prevention (CDC), less than 40 percent of adults</p><p>engage in even two and a half hours of physical activity per week. And</p><p>guess what—women in their forties and older are by far the highest</p><p>demographic to exercise inconsistently. Many don’t exercise at all. This</p><p>drop-off in physical activity comes at a cost and couldn’t come at a worse</p><p>time.</p><p>There’s no shortage of good reasons to be physically active. If you’re</p><p>approaching menopause, there are even more. Physical activity can trigger</p><p>positive hormonal changes that directly reduce the number and severity of</p><p>hot flashes, improve mood, and enhance sleep. It supports cognitive</p><p>strength, too, while boosting your stamina and enhancing your quality of</p><p>life. This news alone should get you on your feet. But there’s more. Medical</p><p>conditions that often make menopause worse or like to pop up</p><p>simultaneously with it, like metabolic issues and insulin resistance, can be</p><p>reduced or even reversed by exercising. Regular physical activity can help</p><p>lower the risk of a seemingly endless list of chronic diseases, including</p><p>heart disease, stroke, high blood pressure, type 2 diabetes, osteoporosis,</p><p>obesity, colon cancer, breast cancer, anxiety, depression, and even</p><p>dementia! If there was a pill for that, we’d all be taking it. What if we</p><p>picked a combo of exercises we liked instead?</p><p>Think about it like this: When it comes to our bodies, everything is</p><p>connected, and there is an undeniable domino effect at work. Exercise can</p><p>stabilize your blood sugar levels, giving you more energy, which in and of</p><p>itself will likely put you in a better mood. More vitality and a better outlook</p><p>might prompt you to keep exercising over time, aiding in weight</p><p>management. Weight management is a great way to keep hot flashes at bay</p><p>while boosting your confidence. A drop in the number of hot flashes</p><p>improves your sleep quality, which can help you manage stress. And so</p><p>forth. Over time, these reciprocal relationships create a positive flow inside</p><p>our bodies and in our lives, turning a vicious cycle into a victorious one.</p><p>Exercise can be a way to take over the reins in menopause, enjoying a new,</p><p>steady gallop where we’d once felt at the mercy of a wild horse.</p><p>There are no two ways about it. Maintaining a consistent exercise</p><p>regimen is a realistic goal for those who wish to have a healthier, smoother</p><p>menopause while setting themselves up for lifelong wellness. The bonanza</p><p>of bonuses exercise brings to the table is evident on multiple fronts, a few</p><p>of which I’m highlighting for you in the following text.</p><p>Healthy Weight and Metabolism</p><p>Around menopause, many women witness an increase in body fat they just</p><p>can’t explain. It’s bad enough that your sleep is disrupted by hot flashes that</p><p>rival the fires of Mount Vesuvius, and that as a result your stress levels are</p><p>off the charts, but now your formerly comfy jeans have turned on you, too.</p><p>It’s understandable to feel frustrated and confused. But don’t scratch your</p><p>head—we’ve caught the culprit.</p><p>It’s a combo attack. When aging, menopause, and a decrease in physical</p><p>activity gang up on you, it can lead to a decline in your metabolic rate and</p><p>lean muscle. Midlife women tend to gain an average of 4 to 5 pounds over</p><p>just a few years. Waist size also increases by about 2.2 centimeters (about 1</p><p>inch). However, contrary to popular belief, while aging may cause weight</p><p>gain, menopause itself does not. It can, however, increase your belly fat.</p><p>How so? Fluctuating levels of estrogen can trigger fat storage in the body,</p><p>and the belly is the storage shed. However inconvenient this may seem,</p><p>there is a method to this madness. As ovarian production of estradiol slows</p><p>down, our body relies on belly fat tissue to produce estrone, estrogen’s</p><p>backup. We actually need that belly fat to ensure that some estrogen</p><p>production continues as we age. However, while having enough body fat</p><p>can help maintain our hormonal health, too much can cause other problems,</p><p>as we know. This shift can result in an apple body shape, usually</p><p>accompanied by a buildup of visceral fat—a stealth fat that collects around</p><p>internal organs, increasing the risk of heart disease and metabolic disorders.</p><p>It’s also true that the drop in estrogen can result in fatigue, achy joints, and</p><p>reduced stamina, making hitting the couch look a lot more inviting than</p><p>hopping off it.</p><p>For some good news, the possible increases in weight and waistline are</p><p>menopause. Do</p><p>you notice how this scan looks darker overall than the first? That change in</p><p>luminosity reflects a 30 percent drop in brain energy.</p><p>This finding was far from being an isolated case; many women enrolled</p><p>in our research program exhibit similar changes, whereas men of the same</p><p>age do not. So what you see here are intense shifts that seem specific to the</p><p>female brain going through menopause. While these changes can account</p><p>for feeling worn out or simply out of sorts (as many can attest to,</p><p>menopause fatigue is nothing to sneeze at), they sink more than your</p><p>energy. They can also impact your body temperature, mood, sleep, stress,</p><p>and cognitive performance. And guess what? Most women can feel these</p><p>changes. When there are marked biological changes at play, resulting in</p><p>actual modifications of the brain’s very chemistry, one can’t help but notice</p><p>them.</p><p>The aforementioned study was only the tip of the iceberg. Over time, our</p><p>investigations yielded a treasure trove of data, demonstrating that it’s not</p><p>just brain energy that changes during menopause but that the brain’s</p><p>structure, regional connectivity, and overall chemistry are also impacted.</p><p>All of this can make for a profoundly mind-blowing, mind-body</p><p>experience. Perhaps less obvious without a brain scanner is that these</p><p>changes don’t occur after menopause—they start before it, during</p><p>perimenopause. Perimenopause is the warm-up act to menopause in which</p><p>you start skipping periods and symptoms like hot flashes tend to make their</p><p>https://www.lisamosconi.com/projects</p><p>first appearance. Our research shows that’s exactly when the brain is going</p><p>through the most profound changes, too. The best way I can explain this</p><p>phenomenon is that the menopause brain is in a state of adjustment, even</p><p>remodeling, like a machine that once ran on gas and is now switching to</p><p>electricity, challenged to find work-arounds. But mostly, these findings are</p><p>scientific evidence of what scores of women have been saying all along:</p><p>menopause changes your brain. So if you’ve ever been told that your</p><p>symptoms are just stress-related or “part of being a woman,” here’s the</p><p>proof that all you’ve been experiencing is scientifically valid and viable.</p><p>The brain is at the crux of the matter, not your imagination.</p><p>How Science Can Help</p><p>Over the years, I’ve spoken to countless women in various states of distress</p><p>due to menopause, especially as related to their brain symptoms (whether</p><p>they could articulate these or not). Many have told me that one of their</p><p>steepest challenges was finding information they could not only readily</p><p>consume but also trust. Hearing and listening to their need for knowledge</p><p>and support made me realize that every woman deserves accurate and</p><p>thorough information about menopause. Peer-reviewed science ensures that</p><p>the ideas are valid, but academic journals are not an efficient way to provide</p><p>this information to the hundreds of millions of women in the real world.</p><p>The Menopause Brain grows out of my commitment to empowering</p><p>women with the information they need to experience menopause with</p><p>knowledge and confidence. Understanding what’s happening inside your</p><p>body and brain before, during, and after menopause is crucial to</p><p>understanding yourself before, during, and after menopause. It is just as</p><p>crucial to take charge of your changing healthcare needs and reclaim your</p><p>agency during this important life transition.</p><p>Thus far, menopause has been painted as an ill-fated, flat-out scary</p><p>roadblock ahead, coming for us one by one. Most of what’s been written</p><p>about menopause, from the scientific literature to online sources, focuses on</p><p>coping or dealing with it, if not even rebelling against it. The vast majority</p><p>of research on the topic has also been focused on what can go wrong with</p><p>menopause and how you can “fix it.” “What’s wrong with that?” you may</p><p>ask. Underlying this approach is the assumption that we can’t hope for</p><p>better than surviving menopause. By treating this life event strictly in a</p><p>biological context, Western medicine has emphasized its downsides and</p><p>minimized its significance. But when you look at menopause from an</p><p>integrative perspective, there is much more at play. In reality, the hormonal</p><p>changes that provoke menopause and its symptoms are simultaneously</p><p>fostering the development of new and intriguing neurological and mental</p><p>skills—ones our society blatantly chooses to ignore. The hidden powers of</p><p>the mind on menopause are the highlights that never make the headlines,</p><p>powers that all women should be aware of. Such awareness leads to new</p><p>means of navigating menopause, and ultimately womanhood itself.</p><p>To this end, the book is divided into four parts:</p><p>Part 1, “The Big M,” provides the foundational elements needed to</p><p>understand what menopause is and isn’t, from a clinical perspective; how it</p><p>impacts the brain; and how we fail to recognize this crucial connection.</p><p>Part 2, “The Brain-Hormone Connection,” discusses the role of hormones for</p><p>brain health and how this interplay is critical in understanding menopause.</p><p>Here, we take a deep dive into understanding how menopause operates</p><p>within the body and brain, which is not just about deciphering the “what”</p><p>but also the “why” of menopause, placing it within a broader context. To do</p><p>so, we will examine what I call the Three P’s: puberty, pregnancy, and</p><p>perimenopause. These are all pivotal times during which our brains,</p><p>hormones, and the give-and-take between them change dramatically.</p><p>Knowledge of the similarities between the Three P’s is key to</p><p>recontextualizing menopause as a natural stage in a woman’s life—a</p><p>moment that, just like the others, can provoke vulnerability as well as</p><p>resilience and positive change. However, if your immediate interest lies in</p><p>finding solutions and seeking ways to feel better, feel free to skip to part 3,</p><p>where we focus on practical strategies and guidance. Part 2 will be there for</p><p>you whenever you’re ready!</p><p>Part 3, “Hormonal and Nonhormonal Therapies,” is a deep dive into hormone</p><p>replacement therapy, as well as other hormonal and nonhormonal options</p><p>for menopause care. We will then review anti-estrogen therapy for breast</p><p>cancer and ovarian cancer, and the effects of “chemo brain.” Finally, while</p><p>throughout the book I use the term “women” to refer to individuals born</p><p>with a so-called female reproductive system (breasts and ovaries), not all</p><p>people who go through menopause identify as women and not all people</p><p>who identify as women go through menopause. In recognition of the</p><p>diverse experiences and identities within the context of menopause, we will</p><p>discuss gender-affirming therapy for transgender individuals, which</p><p>includes methods to suppress estrogen production.</p><p>Part 4, “Lifestyle and Integrative Health,” discusses key validated lifestyle and</p><p>behavioral practices designed to address the symptoms of menopause</p><p>without prescription medications, while also supporting cognitive and</p><p>emotional health. Although you might feel like your brain is all over the</p><p>place, you do have control over your lifestyle, environment, and mindset—</p><p>all of which can impact your experience of menopause in return. There is a</p><p>way to be empowered by embracing and caring for menopause; as we do, a</p><p>wealth of new possibilities is made evident.</p><p>Ultimately, this book is a love letter to womanhood and a rallying cry for</p><p>all women to embrace menopause without fear or embarrassment. It’s the</p><p>foundation to celebrate our own signature brand of brainpower, to</p><p>appreciate the intelligent adaptations our bodies and brains make over the</p><p>course of a lifetime, and to enjoy our journey to optimal lifelong health. I</p><p>hope the information contained in this book will spur many a discussion,</p><p>not only about the multifaceted topic of menopause but also about the way</p><p>in which we have dismissed and marginalized various important parts of</p><p>our population at large. This is crucial not only to shift the conversation</p><p>about menopause but also to reinvigorate the voice of the “forgotten</p><p>gender”—individually, and as half the world.</p><p>temporary for most women, slowing a few years postmenopause. Most</p><p>important, none of this is inevitable. In fact, one of the many ways exercise</p><p>benefits you is by stoking your metabolism and stabilizing your weight.</p><p>This assist is particularly helpful as several studies show that</p><p>perimenopausal and postmenopausal women who engage in regular</p><p>physical activity can greatly improve their body composition, achieving a</p><p>lower body mass index (BMI), less belly fat, and a higher metabolism,</p><p>which allows them to burn calories more easily no matter their age.</p><p>Reduced Risk of Heart Disease and Diabetes</p><p>Heart disease remains the number one cause of death in women over fifty.</p><p>This may be related to the loss of estrogen’s beneficial effects on our</p><p>vascular system, combined with a midlife increase in “bad” LDL (low</p><p>density lipoprotein) cholesterol. The additional accumulation of abdominal</p><p>fat during menopause can increase the risk of insulin resistance and type 2</p><p>diabetes (risk factors for heart disease, in turn).</p><p>But get this: Exercise can lessen or even reverse these risks. As little as</p><p>twelve weeks of training can improve weight, decrease waist</p><p>circumference, and lower triglycerides and total cholesterol in menopausal</p><p>women. At the same time, it promotes healthy blood pressure at all ages.</p><p>Not for nothing, women under sixty who maintain a regular exercise routine</p><p>have a much lower risk of heart disease in their seventies and eighties. The</p><p>bottom line: Physical activity promotes heart health, and what’s good for</p><p>the heart is good for the brain—not to mention the rest of you!</p><p>Reduced Hot Flashes</p><p>Exercise’s power to minimize and potentially prevent menopause-related</p><p>symptoms is making headlines worldwide. Well-established professional</p><p>societies such as the North American Menopause Society and the UK’s</p><p>Royal College of Obstetricians and Gynaecologists recommend regular</p><p>exercise as a valuable intervention for keeping hot flashes at bay. That’s</p><p>because exercise improves the body’s ability to regulate its temperature,</p><p>making us less likely to slam and jam our perspiration button. As mentioned</p><p>earlier, exercise also helps regulate body and fat mass. This one-two punch</p><p>can dramatically decrease the number and severity of hot flashes! In clinical</p><p>trials, women who started out with excess body fat and lost weight by</p><p>exercising during the course of the study reported meaningful reductions in,</p><p>and sometimes complete elimination of, hot flashes in as little as one year.</p><p>Additionally, if hot flashes do occur, the amount of sweating and</p><p>discomfort is significantly reduced in women who exercise regularly. In a</p><p>study of 3,500 Latin American women, those who engaged in regular</p><p>moderate-intensity exercise were 28 percent less likely to have severe hot</p><p>flashes than those who exercised less. In a sample of over 400 Australian</p><p>women, those exercising daily experienced 49 percent fewer hot flashes</p><p>than those who were sedentary. This is quite impressive if you consider that</p><p>taking HRT can reduce hot flashes by about 75 percent. The best news yet</p><p>is that these benefits can be recouped starting right now, even without a</p><p>history of regular exercise. According to several studies, sedentary women</p><p>who take up a fitness routine for the first time in their lives and stick with it</p><p>can experience a marked reduction in hot flashes in as little as three</p><p>months’ time.</p><p>Better Sleep</p><p>The truth is, physically active women sleep better. Higher levels of</p><p>sedentary time are consistently associated with poorer sleep, if not full-</p><p>blown insomnia—all major concerns among women going through</p><p>menopause. On the other hand, physically active perimenopausal and</p><p>postmenopausal women awaken less during the night, have an improved</p><p>quality of sleep, and suffer less from insomnia.</p><p>Better Mood and a Sense of Well-Being</p><p>When we exercise, endorphins, our body’s natural painkillers, flow freely,</p><p>automatically lifting our spirits. Serotonin releases, relaxing and</p><p>“happifying” us. This antidepressant effect is linked to a drop in stress</p><p>hormones, and everyone could use some of that. The result: Midlife women</p><p>with greater physical activity consistently report a better quality of life, a</p><p>heightened sense of psychological well-being, and reduced symptoms of</p><p>depression and anxiety—both before and after menopause. In a combined</p><p>analysis of eleven clinical trials totaling almost 2,000 midlife women,</p><p>regular exercise significantly reduced depressive symptoms, as well as</p><p>stress and related insomnia, after just twelve weeks. Both moderate and</p><p>low-intensity exercise regimens worked like a charm. Since not everyone is</p><p>into (or capable of) high-intensity workouts, this is good news indeed.</p><p>Better Memory and a Lower Risk of Dementia</p><p>Exercise is not only muscle-building, stress-busting, and endorphin-</p><p>releasing—it is also memory-enhancing. For example, in a study of</p><p>thousands of elderly people, those who engaged in regular physical activity</p><p>had a 35 percent lower risk of developing dementia than those who were</p><p>sedentary. You should note that many of these activities were not in gyms</p><p>but were done in street clothes, like walking, biking, climbing stairs, and</p><p>doing household chores.</p><p>For our purposes, a recent study followed about 200 midlife women for</p><p>as long as forty-four years. The results show that those with the highest</p><p>level of cardiovascular fitness in midlife had a whopping 30 percent lower</p><p>risk of developing dementia as they got older compared to those who</p><p>remained sedentary. As a dementia specialist, I can assure you that a 30</p><p>percent reduction in the rates of dementia is nothing short of extraordinary</p><p>—so far, no drug has achieved such an effect. Sure enough, our brain-</p><p>imaging studies also demonstrate that physically active midlife women</p><p>exhibit more vigorous brain activity, less brain shrinkage, and fewer</p><p>Alzheimer’s plaques as compared to their sedentary counterparts. These</p><p>fantastic results contribute to maintaining a clear head and long-lasting</p><p>memories.</p><p>Stronger Bones and Fewer Injuries</p><p>One of exercise’s most sought-after benefits is the miracle it works on bone</p><p>density. When we strengthen our muscles, we strengthen our bones.</p><p>Physical activity effectively slows bone loss after menopause, lowering the</p><p>risk of fractures and osteoporosis. Reducing the likelihood of falls and</p><p>injuries improves our mobility and reduces our pain potential, during</p><p>menopause and beyond.</p><p>Increased Longevity</p><p>The following is not hyperbole: Staying active can actually save your life. It</p><p>is not my intention to freak you out with the statistics below, but let’s not</p><p>mince words—the more time you spend sitting and lying down with little to</p><p>no exercise, the higher your risk of, well, dying.</p><p>To give you some examples, in the Women’s Health Initiative, among</p><p>over 92,000 postmenopausal women ages fifty to seventy-nine, those who</p><p>reported the lowest amounts of sedentary time showed a significantly</p><p>reduced risk of mortality compared to their physically inactive counterparts.</p><p>Specifically, those who spent more than five hours per day being physically</p><p>active were 27 percent less likely to die of heart disease and 21 percent less</p><p>likely to die of cancer than those who spent eight hours or more per day in</p><p>sedentary mode. (Ah, no, that doesn’t include time spent sleeping.) More</p><p>striking evidence comes from the Nurses’ Health Study, which revealed</p><p>similar findings among younger women, ages thirty-four to fifty-nine.</p><p>When these women reached their seventies and eighties, those who had</p><p>been physically active had a 77 percent lower risk of respiratory death, a 31</p><p>percent lower risk of dying from heart disease, and a 13 percent lower risk</p><p>of dying from cancer than those who were mostly sedentary. Well then, time</p><p>to get moving.</p><p>WHAT KIND OF EXERCISE IS BEST?</p><p>Everyone struggles to find enough me time. Is there some way we can</p><p>exercise smarter rather than harder? Are there certain kinds of exercise that</p><p>favor women of menopausal age? How about older women? The top</p><p>questions about training</p><p>are how hard, how often, how long, and what type</p><p>of exercise can really make the cut.</p><p>How Often</p><p>Before menopause. Here the target is four to five 45-to-60-minute</p><p>sessions a week. Research shows this formula is particularly</p><p>effective at supporting hormonal health and even fertility.</p><p>Remember, the longer you’re fertile, the later you go through</p><p>menopause.</p><p>For traversing menopause through age sixty-five or so. During this</p><p>period we tailor the recipe to three to five days a week, at 30 to 60</p><p>minutes a clip, and adjust the duration and intensity of the workout</p><p>based on age, severity of symptoms, and overall health and fitness</p><p>level. Obviously, if you can do more, do more.</p><p>After age seventy. Daily sessions of at least 15 minutes each are a</p><p>good rule of thumb, though many women can (and will) do more</p><p>than this.</p><p>How Hard</p><p>There’s a recurrent myth that the older you get, the harder you have to</p><p>exercise to see results. Rigorous research on this topic shows precisely the</p><p>opposite. Especially for postmenopausal women, moderate-intensity</p><p>exercise serves you better than intense bursts of effort. Remember, we’re</p><p>not talking about bodybuilding here; we are targeting your overall health.</p><p>In midlife, the relationship between exercise intensity and health looks</p><p>like an upside-down U. As shown in figure 9, a low-intensity exercise</p><p>yields some health gains, but moderate-intensity is where the action is,</p><p>providing the maximum return. Increasing your workouts to a high-</p><p>intensity range doesn’t seem to improve the benefits; perhaps surprisingly,</p><p>it shows diminishing returns. Regular moderate-intensity exercise has been</p><p>linked to the lowest risk of heart disease, stroke, diabetes, and cancer in</p><p>women, starting around midlife. As another incentive, it’s also associated</p><p>with better sleep.</p><p>Figure 9. Exercise intensity and health gains in midlife women</p><p>With all the buzz around boot camps, boxing, stationary biking</p><p>(spinning), and high-intensity interval training, you might wonder why</p><p>moderate-intensity exercise is so effective. First, it’s important to point out</p><p>that none of the above programs are developed with female physiology in</p><p>mind, let alone any awareness of menopause. They target trends based on a</p><p>very specific demographic and then sell the program as good for everybody.</p><p>The truth is, they’re not good for everybody. And guess what? Scientists</p><p>have found that high-intensity training clearly benefits men, whereas cardio</p><p>and resistance training at a moderate intensity work better for women. This</p><p>difference may be because high-intensity exercise increases the stress</p><p>hormone cortisol—which most women already have plenty of. High-</p><p>intensity workouts also require more sleep and rest to recover from—an</p><p>elusive commodity in a woman’s world.</p><p>Let’s clarify what constitutes moderate-intensity exercise. We are not</p><p>talking about a leisurely stroll (though that’s certainly better than nothing, if</p><p>it’s all you have time or energy for). Moderate intensity is any exercise that</p><p>ups your heart rate and enables you to break a light sweat. To achieve this,</p><p>you should move fast enough to get your blood flowing, bringing roses to</p><p>your cheeks. Although you might have a little breathiness when talking, you</p><p>shouldn’t struggle to catch your breath. Singing out loud, however, should</p><p>be a challenge.</p><p>To be clear, I’m not saying ditch your bigger dumbbells and to heck with</p><p>push-ups. There are plenty who can do all of that and then some. I am</p><p>saying that the sweet spot for our purposes is exercising more often at a</p><p>moderate intensity. This rhythm ensures you exercise consistently enough at</p><p>just a high-enough intensity to get the payoff you deserve and need.</p><p>What Type</p><p>For maximum benefit, experts recommend focusing on three types of</p><p>exercise: aerobic, strengthening, and flexibility and balance.</p><p>▷ AEROBIC EXERCISE</p><p>If you want more bang for your buck, start with aerobic exercise. This type</p><p>of exercise has long been praised as most effective for everything under the</p><p>sun. It raises your heart rate, enhances your blood flow and circulation, and</p><p>pumps oxygen and nutrients throughout your body. This in turn protects</p><p>your heart against plaque while clearing your head and sharpening your</p><p>mind. As if this weren’t enough, aerobic exercise is the best regimen to foil</p><p>hot flashes, too.</p><p>But again, you don’t need to sign up for CrossFit or start prepping for a</p><p>marathon to reap its benefits. Walking, hiking, or an elliptical machine all</p><p>do the trick. Multiple clinical trials report that even an activity as simple as</p><p>brisk walking can significantly improve your health in as little as three</p><p>months. Brisk means walking in a hurry, like you’re late for an</p><p>appointment. In multiple studies, brisk walking for 30 minutes three times a</p><p>week was effective at reducing insomnia, irritability, and fatigue in midlife</p><p>women. It also improved weight and waist circumference and lowered</p><p>triglycerides and total cholesterol. Plus, walking slows down brain</p><p>shrinkage, effectively protecting us against brain fog and memory decline.</p><p>In practical terms, walking 6,000 or more steps per day is associated with a</p><p>decreased risk of heart disease and diabetes in women ages forty and over.</p><p>Augmenting that target toward 9,000 to 10,000 steps may lower your risk of</p><p>dementia, too.</p><p>Other examples of properly paced exercise are bike riding at 7 to 10</p><p>miles per hour, hopping on the elliptical machine at a steady stride, jumping</p><p>rope, swimming, exercising in the water, playing tennis, attending group</p><p>fitness classes, dancing, or stair climbing. Remember that you can combine</p><p>these things into your own quirky customized routine. Any exercise that</p><p>keeps you on your feet also helps preserve bone mass and prevent</p><p>osteoporosis.</p><p>For those who don’t have the extra time or resources to hit the gym or</p><p>take long walks, let’s remember the accumulated effect of everyday</p><p>activities like gardening, cleaning the house, and running chores, not to</p><p>mention running after your kids or grandkids. These activities may not</p><p>achieve the same effects as more intense exercise, but sources say that</p><p>engaging in one hour a day of low-intensity physical activities has a</p><p>favorable effect on menopause symptoms and overall quality of life.</p><p>▷ STRENGTHENING</p><p>The latest evidence points to the power of pairing up moderate-intensity</p><p>aerobic exercise with weight-bearing exercises for maximum benefits for</p><p>women. While aerobic exercise targets metabolic health and reduces hot</p><p>flashes, these strengthening exercises are particularly effective at reducing</p><p>anxiety and brightening your mood.</p><p>Training with free weights, weight machines, or resistance bands can</p><p>help add muscle mass to your body, thereby stimulating bone-building and</p><p>boosting metabolism. Body-weight exercises like push-ups and pull-ups, as</p><p>well as knee raises, planks, lunges, and squats, also build muscle, support</p><p>bone health, and improve your core strength and balance. Choose whatever</p><p>weight or resistance level is just heavy enough to feel the burn when doing</p><p>15 reps. Gradually increase the weight or resistance level as you get</p><p>stronger.</p><p>▷ FLEXIBILITY AND BALANCE EXERCISES</p><p>These are plentiful and include things like yoga, mat Pilates, tai chi, and</p><p>stretching. All can improve your coordination, keep you steady on your</p><p>feet, and ward off falls and arthritis down the line. Yoga and Pilates also</p><p>incorporate specialized breathwork into the exercises, promoting relaxation</p><p>and hormonal balance as they tone your core. Studies show that this kind of</p><p>workout, in particular, can release stress and support quality sleep.</p><p>We’ll talk more about mind-body techniques in chapter 16, but just to</p><p>reinforce the importance of balance and flexibility, it’s time for a spookily</p><p>telling test. Can you balance on one leg for 10 seconds or longer?</p><p>It turns out that poor balance is linked to frailty in older age, and is also a</p><p>prime indicator of declining health. Women under seventy years of age are</p><p>pretty much expected to pass this test without blinking an eye. If that’s you,</p><p>great—now</p><p>make it a whole minute. If you are older than seventy and</p><p>complete the task easily, congratulations, you are in better shape than many</p><p>of your peers. If instead you cannot balance on one foot for 10 seconds,</p><p>regardless of your age, you may be in jeopardy of nearly double the</p><p>likelihood of a rapid health decline in the next decade or so. If this isn’t</p><p>motivation to sign up for that yoga class, I don’t know what is!</p><p>STAY MOTIVATED</p><p>Most studies, including many clinical trials, indicate that you should start</p><p>harvesting the fruits of your labor in as little as twelve weeks when you</p><p>follow the above guidelines. However, even though most people are aware</p><p>that exercise is well worth doing, many resist. The most common obstacles</p><p>are money, time, and motivation.</p><p>There’s a general misconception that to exercise regularly, one must drop</p><p>a large chunk of change to join a gym or invest in expensive fitness</p><p>equipment. But seriously, there’s no need. Walking, hiking, running, or</p><p>riding a bicycle if you have one are free and fun ways to exercise. Smaller</p><p>pieces of equipment such as an exercise ball, dumbbells, or resistance bands</p><p>can be used for a variety of exercises and are super-efficient (and</p><p>inexpensive). There are also workout routines that don’t require a single</p><p>piece of equipment, many of which you can find for free online and on</p><p>YouTube.</p><p>Lack of time is a tricky one to solve. Just the same, it might be the most</p><p>common reason women do not exercise. Our schedules are stuffed with</p><p>work, family, children, and various other responsibilities, or all of the</p><p>above, so exercise is tough to fit in. While this is a legitimate challenge, we</p><p>need to keep our eyes on the prize: more energy, better sleep, better mood,</p><p>clearer heads, less stress, fewer flashes—and the list goes on. So the</p><p>question is not whether it’s doable but how to make it happen. Whether it’s</p><p>a matter of prioritizing it or finding sneaky ways to slip movement into your</p><p>daily routine, here are some tips that may help:</p><p>Schedule a time each day for exercise. Write it on your calendar and</p><p>stick to it as best you can.</p><p>Break it up. If you don’t have a 60-minute window to exercise, you</p><p>might find three 20-minute segments in which you can.</p><p>If you don’t have more than 20 minutes, then work out for 20</p><p>minutes. Never underestimate the power of a quick workout! There</p><p>is still an enormous difference in overall health compared to doing</p><p>nothing at all.</p><p>If you are seriously strapped for time, plank. Get yourself in plank</p><p>position and hold it for as long as possible. Ten minutes in plank</p><p>pose may be as challenging as an hour of squats.</p><p>If you worry about what to do with your family while you exercise,</p><p>find a way to exercise together. Take a family walk, play ball in a</p><p>park or backyard, go for a bike ride, skip rope, or invest in a small</p><p>trampoline that you can keep inside. When my daughter was little,</p><p>I’d do my yoga routine while she climbed me like a jungle gym. She</p><p>became my favorite free weight, and I was as popular as going to</p><p>the playground!</p><p>Look for free classes online. If you have the resources, you might</p><p>consider finding a personal trainer who will help you develop a</p><p>routine customized to you and your schedule. Many offer Zoom or</p><p>Skype sessions, cutting out the commute and making it all the more</p><p>convenient.</p><p>Track your progress to increase your motivation and staying power.</p><p>As helpful as various gadgets can be, you don’t need an Oura ring or</p><p>an Apple Watch. There are unlimited ways to keep tabs on your</p><p>physical activity. Just write down how often and how much you’ve</p><p>exercised, what you did, how you felt. If you can get a simple step</p><p>tracker, that can also help you stay on target.</p><p>Finally, persistence is paramount. So many people try a form of exercise</p><p>that’s not a fit and find themselves quitting before they even start. This can</p><p>happen to the best of us, whether we don’t see changes in our bodies fast</p><p>enough or perhaps get discouraged by unattainable goals. Here’s what I</p><p>think: Forget about the celebrities who look twenty-five when they’re in</p><p>their fifties, especially those setting impossible standards. Remember that</p><p>they employ entire teams of personal trainers, stylists, surgeons, and chefs</p><p>to get them camera-ready. Define what fitness and health mean for you</p><p>instead.</p><p>It’s also worth considering that some people just don’t like to exercise. If</p><p>this is you, I can’t stress enough how important it is to find ways to keep</p><p>your body moving that you actually enjoy and find sustainable. Some</p><p>people like the competitive aspect of exercise (sports), some like the social</p><p>aspect (classes), some love the solitary quality (solo walks), and some enjoy</p><p>having fun (dancing). Perhaps a daily trip to the gym is not for you. You</p><p>may enjoy walking or biking outdoors more or doing yoga in the park. Or</p><p>maybe you do love going to the gym but feel weird going it alone. Then</p><p>join a class or group, or team up with a workout buddy. On the other hand,</p><p>if going solo is your thing, go for a walk (shooting for those 6,000 or more</p><p>steps) or crank up some music and dance like no one is watching. Whatever</p><p>the case, where there’s a will, there’s a way. Decide what you value</p><p>regarding your health goals and be the boss of your wellness. Set realistic,</p><p>achievable goals for yourself, and approach these goals with self-love</p><p>instead of self-criticism. Get creative, and you do you.</p><p>14</p><p>Diet and Nutrition</p><p>FOOD FOR THOUGHT</p><p>In our society, we focus more on dieting to whittle our waistlines than to</p><p>nourish ourselves. We definitely have this backward! Being selective about</p><p>what we put in our mouths is central to our health and well-being at any</p><p>stage of life, and it’s just as important when it comes to the health of our</p><p>brains.</p><p>Neuro-nutrition, or nutrition for the brain, is a big part of my world. As a</p><p>brain scientist, I am acutely aware of the importance of food for brain</p><p>health. This is for three main reasons. First, our brains rely on specific</p><p>nutrients to function properly. Second, our brain cells are, in very large part,</p><p>made of the foods we eat. Meal after meal, day after day, those foods—and</p><p>more specifically, the nutrients they contain—become the very fabric of our</p><p>brains. Last, our brain cells are built in a unique way compared to the cells</p><p>that make up our other organs. Unlike the rest of the body, where cells are</p><p>constantly rebuilt and replaced, most of our brain neurons are irreplaceable.</p><p>They are born with us and stick with us for most of our lives. With this in</p><p>mind, the next time you are torn between eating a meal of fresh whole foods</p><p>or a greasy fast-food cheeseburger, you may want to pause and decide with</p><p>which you want to fill your head.</p><p>When it comes to women’s health, not only does smart nutrition have a</p><p>proven impact on our body composition and energy levels, but it can also be</p><p>a powerful ally against aging, disease, and—you guessed it—menopause.</p><p>The key here is to eat smart by focusing on filling your plate with nutrient-</p><p>dense foods, which are particularly rich in nutrients that work in your favor,</p><p>such as vitamins, minerals, fiber, complex carbohydrates, lean protein, and</p><p>healthy fats. Besides being nutritious and delicious, smart foods can reduce</p><p>inflammation and bolster your resilience against stress; they can brighten</p><p>your mood and clear your head. They can help you sleep better, feel better,</p><p>and perform better. On top of that, there is evidence that select foods have a</p><p>positive impact on hormonal health, easing a woman’s monthly cycles, and</p><p>both delaying the onset of menopause and reducing the frequency and</p><p>severity of its bothersome symptoms. The reverse, however, is also true. A</p><p>poor diet can indeed make symptoms worse, hasten the onset of menopause,</p><p>and make you feel cranky, tired, depleted, and brain fogged. When you’re</p><p>going through perimenopause in particular, you may begin to notice that</p><p>certain foods trigger certain symptoms. For example, foods that spike blood</p><p>sugar levels can suddenly zap your energy and leave you more irritable than</p><p>ever.</p><p>Drinking alcohol can exaggerate, extend, or multiply hot flashes.</p><p>Refined, processed, and preservative-heavy foods are expert at taking down</p><p>your mood and focus, killing two precious birds with one stone.</p><p>It is important, then, to learn which foods and nutrients are supportive of</p><p>our brain health in general—and our brain health in menopause in particular</p><p>—and which foods and nutrients have the exact opposite effect and should</p><p>be avoided. At the same time, how to eat is just as important as what to eat.</p><p>As menopause becomes more newsworthy, you’ll see diets popping up left</p><p>and right, claiming to tame it. Be cautious of these trends. They have little</p><p>to do with menopause and everything to do with picking your pocket.</p><p>Marketers jump at the chance to capitalize on our vulnerability as we dream</p><p>of a flatter belly without the energy to obtain it. Some will go as far as to</p><p>recommend you consume no more than 800 calories a day, advice that is</p><p>not only unsustainable but reckless. One thing we’ve learned from decades</p><p>of research is that diets based on extremes fail spectacularly in the end. Not</p><p>only won’t they deliver the promised results, but they often tamper with the</p><p>delicate integrity of our bodies, brains, and hormones in the process. So I</p><p>hope you’re ready to throw some shade on ten-day cucumber cleanses, fad</p><p>diets, and get-fit-quick ploys as we review the actual science on nutrition</p><p>for menopause.</p><p>THE “GREENER” MEDITERRANEAN DIET</p><p>The best way to clarify which diets really work is to look at both science</p><p>and tradition. Science speaks as to why particular diets work, while</p><p>tradition lets us know if they’ve stood the test of time. When science meets</p><p>tradition and the two agree, we’re definitely on the right track.</p><p>Enter the Mediterranean diet.</p><p>Long praised as one of the world’s healthiest diets, the traditional</p><p>Mediterranean diet has well-documented protective effects on brain, heart,</p><p>gut, and hormones—bestowing a reduced risk of heart disease, stroke,</p><p>obesity, diabetes, cancer, depression, and dementia as compared to most</p><p>other diets! When it comes to women’s health in particular, the</p><p>Mediterranean diet works like a charm, with positive effects on blood</p><p>pressure, cholesterol, and blood glucose levels. As a result, women on a</p><p>Mediterranean-style diet boast a 25 percent lower risk of heart attack and</p><p>stroke than those following a Western-style diet high in processed foods,</p><p>meat, sweets, and sugary beverages. Additionally, those who follow the</p><p>Mediterranean diet in midlife have at least a 40 percent lower risk of</p><p>developing depression in old age as compared to those on less healthy diets.</p><p>They also have half the risk of breast cancer.</p><p>In more good news, women who follow a Mediterranean diet experience</p><p>a generally milder menopause with far fewer hot flashes. For example, in a</p><p>study of over 6,000 women who were experiencing menopausal symptoms,</p><p>those who went on this diet experienced a 20 percent decrease in hot</p><p>flashes and night sweats. Additionally, this diet pattern may delay the onset</p><p>of menopause, too. A large examination of dietary data collected from</p><p>14,000 women revealed that consumption of legumes, like peas or beans,</p><p>and fish is associated with a later onset of menopause by as many as three</p><p>years. The other side of the story wasn’t quite so pretty. Women who</p><p>consumed less of these healthy foods and more processed foods and refined</p><p>carbs like white rice and pasta exhibited an accelerated onset of menopause</p><p>instead. These data also correlate with the fact that many women on a</p><p>typical Western diet enter menopause early and suffer its effects more</p><p>severely.</p><p>So how does the Mediterranean diet achieve such impressive benefits?</p><p>At a glance, it is low in calories and high in fiber, healthy fats, and</p><p>complex carbohydrates—all key components of the nutrient-dense foods we</p><p>discussed above. It contains no refined sugars or processed foods, a</p><p>hallmark of good health we can’t ignore. From a nutritional perspective, the</p><p>Mediterranean diet is considered plant-centric, without being overly</p><p>restrictive. Fresh vegetables and fruit, whole grains, legumes, and a variety</p><p>of nuts and seeds are the stars of the show. Small amounts of seafood, eggs,</p><p>or poultry are other typical entrées, while dairy and red meat are consumed</p><p>sparingly and in moderation. Unrefined plant oils, like extra-virgin olive oil</p><p>and flax oil, are the condiment of choice, paired with local vinegar or a</p><p>squeeze of lemon juice. Bouquets of herbs and spices are used to flavor</p><p>foods instead of table salt. Meals are often accompanied by a glass of red</p><p>wine and finished off with a fragrant espresso—both rich sources of</p><p>antioxidants. Desserts, including handmade pastries and artisanal gelato</p><p>(made with high-quality ingredients), are not a daily event but are eaten</p><p>with gusto on weekends or special occasions. The resulting combo platter is</p><p>potent in antioxidants, polyphenols, fiber, and heart-healthy unsaturated fats</p><p>—while allowing enough flexibility that one won’t feel deprived.</p><p>Still, as potent as this diet can be, experts believe that a few tiny tweaks</p><p>on the plan can make it even better for you. This healthy-fied Green</p><p>Mediterranean diet further reduces the amount of meat on the menu and</p><p>promotes plant-based protein instead, while introducing additional nutrient-</p><p>dense foods that are not typically found in the Mediterranean region, such</p><p>as green tea, avocados, and soybeans. This combination seems to amplify</p><p>the benefits of the diet, leading to more fat loss around the midsection (the</p><p>apple shape we discussed in the last chapter) and greater metabolic wins, as</p><p>well as lower blood pressure, lower bad cholesterol, better insulin</p><p>sensitivity, and less chronic inflammation. Additionally, while both dietary</p><p>patterns slow the shrinkage of the hippocampus (that brain region that</p><p>impacts our ability to learn and remember), the Green Mediterranean diet</p><p>seems to offer potentially higher protection against aging and disease.</p><p>While I’m not asking you to follow this diet to the letter, I would</p><p>recommend trying this greener option, which we’ll review below.</p><p>Before we begin, one of the many misconceptions regarding the</p><p>Mediterranean diet is that it can be exclusive and/or expensive. I can assure</p><p>you that this is not the case. The key is knowing what a real Mediterranean</p><p>diet is, and not falling into the trap of all the inspired menus full of fancy</p><p>ingredients, expensive wines and cheeses. The authentic Mediterranean diet</p><p>is not expensive, by any standards. It involves local wine and seasonal</p><p>produce, along with beans and whole grains as the main source of protein.</p><p>As I mentioned earlier, meat and dairy—which are typically more</p><p>expensive than produce—are more occasional indulgences. If you are</p><p>interested in some tips on how to eat healthy without breaking the bank, I</p><p>shared many in my first book, Brain Food. Here, the focus is on specific</p><p>foods and nutrients that can be helpful with hormonal health and</p><p>menopause. For some, most of these foods will be available at your local</p><p>supermarket. For others, some foods may be difficult to come by or might</p><p>be too expensive. In that case, simply swap them out for other options; this</p><p>is more about a dietary approach than a strict plan or a shopping list. By</p><p>focusing on a variety of plant-based whole foods, keeping an eye on your</p><p>use of animal products, and staying away from ready-to-eat meals and</p><p>processed foods, you’ll improve your nutritional health in no time.</p><p>UP YOUR PLANT GAME</p><p>While you might be familiar with the old adage “Food is medicine,” the</p><p>truth is, plants are medicine. Plant foods are high in vitamins, minerals, and</p><p>a bounty of phytonutrients, which help fight disease, reduce inflammation,</p><p>and promote resilience throughout the entire body. Just as important, plants</p><p>are the richest source of fiber, and fiber is the name of the game in women’s</p><p>health. In fact, some of the most potent nutritional advice I can deliver is to</p><p>eat enough fiber.</p><p>Besides its positive effects on blood sugar, insulin levels,</p><p>and digestion,</p><p>fiber has the lesser-known skill of balancing estrogen levels. It facilitates</p><p>the action of a molecule called sex hormone binding globulin, or SHBG,</p><p>which regulates estrogen and testosterone levels in blood, effectively</p><p>stacking hormones in our favor. As a result, eating enough fiber is a</p><p>fantastic first-line defense against menopausal symptoms like hot flashes,</p><p>which tend to be fewer and milder with fiber-rich diets. The balance fiber</p><p>achieves in our bodies is essential for women in general, and for breast</p><p>cancer survivors in particular. In the Women’s Healthy Eating and Living</p><p>Study, women treated for early stage breast cancer who consumed a high-</p><p>fiber diet experienced a significant decrease in hot flashes in as little as one</p><p>year. This study was only one among many showing clear-cut results. How</p><p>much fiber is enough? As a rule of thumb, that’s approximately 14 grams of</p><p>fiber for each 1,000 calories you consume each day. For example, if you</p><p>consume 2,000 calories per day for healthy weight maintenance, you should</p><p>consume 28 grams of fiber.</p><p>Another big plus of eating more plant-based foods is that they offer some</p><p>of the richest antioxidant choices available on the planet. Antioxidants fight</p><p>off free radicals, reducing inflammation and delaying cellular aging. Since</p><p>free radicals negatively affect egg maturation and release, while also</p><p>wreaking havoc on your brain cells, a high intake of antioxidants may slow</p><p>these effects, postponing menopause for longer. Among the mightiest</p><p>antioxidants are vitamins C and E, beta-carotene, and the rare mineral</p><p>selenium, along with a variety of phytonutrients, such as lycopene and</p><p>anthocyanins, which grant blueberries, tomatoes, and grapes their beautiful</p><p>red and blue hues. While you may think you know the top antioxidant-</p><p>containing foods (let me guess... blueberries?), some might surprise you:</p><p>blackberries, goji berries, and artichokes pack an even more powerful</p><p>punch. Some spices and herbs, such as cinnamon, oregano, and rosemary,</p><p>also compete, and citrus fruits famously show off in the vitamin C</p><p>department. When it comes to selenium, Brazil nuts are a great source, but</p><p>you can also find it in rice, oats, and lentils.</p><p>FRUIT AND VEG</p><p>Remember in the old-school cartoons when Popeye devoured his spinach</p><p>straight from the can to flex rapid-fire muscles that saved the day?</p><p>Although spinach alone may not accomplish miracles, eating more veggies</p><p>may indeed do the trick.</p><p>Greens in particular are the foods least consumed in the standard Western</p><p>diet, yet are the most essential for our health. Today, only one in every ten</p><p>American adults consumes the minimum daily requirements for fruit or</p><p>vegetables. In contrast, one in every two Americans eats 200 pounds of red</p><p>meat and poultry each year—and that’s on top of all the processed foods</p><p>consumed daily. Between these stats and those regarding lack of exercise,</p><p>almost half of all U.S. adults will be obese by 2030. The rates of heart</p><p>disease, stroke, and type 2 diabetes are also at an all-time high in many</p><p>countries. Who’s leading the pack? Sadly, women are winning that race, so</p><p>we really need to pay closer attention to our food choices.</p><p>Many common chronic diseases are heavily impacted by diet, making it a</p><p>no-brainer to optimize our foods in ways conducive to our health. To this</p><p>end, most experts recommend we “eat the rainbow,” consuming a wide</p><p>array of colorful fruits and veggies at every meal. As a rule of thumb,</p><p>vegetables should make up half of your plate in any given lunch or dinner.</p><p>Among them, dark leafy greens and cruciferous vegetables are</p><p>exceptionally conducive to hormonal balance and a healthy nervous system.</p><p>For some examples, these include:</p><p>Leafy green vegetables: kale, collard greens, spinach, cabbage, beet</p><p>greens, watercress, romaine lettuce, Swiss chard, arugula, and</p><p>endive.</p><p>Cruciferous vegetables: cauliflower, broccoli, cabbage, kale, collard</p><p>greens, mustard greens, garden cress, bok choy, Brussels sprouts.</p><p>Women who eat plenty of these veggie heroes have lower odds of being</p><p>overweight or obese and far fewer menopausal symptoms than those who</p><p>skip the veg and fill in the difference with fast food, processed foods, and</p><p>commercially farmed meat and dairy. For instance, in a one-year</p><p>intervention involving over 17,000 menopausal women, those eating more</p><p>fiber-rich veggies, fruits, and beans experienced a 19 percent reduction in</p><p>hot flashes compared with those who ate fewer plant-based foods.</p><p>Likewise, a study of 393 postmenopausal women revealed that those eating</p><p>more leafy greens and cruciferous vegetables had fewer menopausal</p><p>symptoms while enjoying higher energy. Moreover, regular consumption of</p><p>cruciferous vegetables may reduce damage to your genes, protecting you</p><p>against breast cancer in turn. It is also associated with 50 percent lower</p><p>odds of experiencing severe menopausal symptoms among breast cancer</p><p>patients.</p><p>Let’s not stop there. Low-to-medium glycemic vegetables like onions,</p><p>beets, pumpkin, and carrots are also excellent choices, as is fruit. While</p><p>some diets recommend avoiding fruit due to its sugar content, there’s plenty</p><p>of evidence that many fruits are uniquely beneficial to women’s health and</p><p>shouldn’t be missed. In a study that followed 6,000 women for about nine</p><p>years, those who ate fruit more regularly—especially strawberries,</p><p>pineapple, melons, apricots, and mangoes—had 20 percent fewer hot</p><p>flashes and were in much better spirits compared with those who didn’t eat</p><p>as much fruit. Citrus fruit rich in antioxidant vitamin C, such as oranges,</p><p>limes, lemons, grapefruit, and kumquats, also helped reduce a variety of</p><p>symptoms. Another good reason to eat fruit: A study of over 16,000 women</p><p>followed over many years showed that those who consumed flavonoid-rich</p><p>berries, like blueberries and strawberries, had better cognitive performance</p><p>than those who didn’t. One or two servings of fresh fruit per day will do the</p><p>trick. However, if you’re particularly concerned about sugar, favor low-</p><p>glycemic fruit like berries, apples, lemons, oranges, grapefruit, and</p><p>watermelon—and eat higher-glycemic fruits like grapes and mangoes more</p><p>sparingly.</p><p>WHOLE GRAINS, STARCHES, AND LEGUMES</p><p>While most people acknowledge that fruit and vegetables should be part of</p><p>a healthy diet, there is debate over whether grains, potatoes, and legumes</p><p>are friends or foes. Many have been taught to beware of carbs without</p><p>realizing that not all carbs are created equally. In fact, carbohydrates can be</p><p>simple or complex based on how much fiber, starch, and sugar they contain.</p><p>Foods containing more fiber than sugar are typically called complex carbs</p><p>and have a lower glycemic load. As a result, they are gentler on the body,</p><p>slowly releasing their natural sugars, which are readily metabolized into</p><p>energy without causing spikes in your insulin levels. Whole grains (those</p><p>with the husk still on) like brown rice, wheat berries, and steel-cut oats, as</p><p>well as most legumes and tubers like sweet potatoes, fall in this complex</p><p>carb category, explaining why they are also referred to as “good” carbs.</p><p>From a women’s health perspective, eating low-glycemic carbs has been</p><p>linked to very favorable outcomes, such as a markedly lowered risk of heart</p><p>disease, type 2 diabetes, depression, and dementia—not to mention better</p><p>sleep!</p><p>On the other end of the spectrum are high-glycemic carbs, possessing a</p><p>high dose of sugar, likely refined sugar at that, and little to no fiber. These</p><p>foods, sometimes labeled “bad” carbs, trigger spikes in blood sugar levels,</p><p>making it hard for your body’s insulin to metabolize so much quick sugar at</p><p>once. Over time, this exhausts your pancreas, causing insulin resistance.</p><p>Insulin resistance inflames your body and its systems, posing a risk factor</p><p>for metabolic disorders, diabetes, and heart disease. It can also harm</p><p>estrogen production, the last thing anyone needs. Great examples of high-</p><p>glycemic carbs aren’t just the obvious ones like packaged treats, sugary</p><p>cookies, commercial pastries, and</p><p>candies. The high-sugar carb club has</p><p>numerous members, including sodas, sweetened drinks, and processed</p><p>grains such as sandwich bread, white bread, white rice, commercial pasta,</p><p>bagels, and rolls.</p><p>Folks, the jury’s in. If we want to optimize our health as women, whole</p><p>grains and legumes are in; refined grains are out. Sweet potatoes and</p><p>regular potatoes with the skin on are also in; processed potato-based</p><p>products and French fries from McDonald’s are out. You get the idea.</p><p>For those who avoid gluten, naturally gluten-free whole grains such as</p><p>rice (brown, red, black), wild rice (technically a seed), quinoa (also a seed),</p><p>amaranth, buckwheat, millet, sorghum, and teff are legitimate sources of</p><p>good carbs. But beware of the many gluten-free products masquerading as</p><p>healthy alternatives while they’re nothing more than yet another processed</p><p>junk food.</p><p>NATURAL SWEETENERS</p><p>We’d all do well to ditch white sugar and artificial sweeteners once and for</p><p>all. Natural unrefined ones like raw honey, maple syrup, stevia, and coconut</p><p>sugar are a whole other thing. Richer in vitamins and minerals than the</p><p>powdery or granular white stuff, these sweeteners are gentler on the body</p><p>and don’t pound as hard at your blood sugar levels. If you, like me, can’t</p><p>function without the occasional treat, I strongly recommend dark chocolate</p><p>with a cacao content of 80 percent or higher. Or better yet, try raw dark</p><p>chocolate. In its purest form, this type of chocolate is a powerful superfood</p><p>with an impressive health pedigree. It has a low glycemic load, is satisfying</p><p>without a sugar crash, and it’s rich in theobromine, a kick-ass antioxidant.</p><p>Also packing powerful flavonols that combat inflammation and estrogen-</p><p>supporting catechins, raw chocolate is a welcome treat. For some</p><p>inspiration, I am going to share one of my all-time favorite recipes: a</p><p>delicious three-ingredient dark chocolate ganache. Begin by melting ½ cup</p><p>of unsweetened dark chocolate chips and ¼ cup of unrefined coconut oil.</p><p>Then stir in 1 heaping tablespoon of raw cacao powder and a tablespoon of</p><p>maple syrup. Pour the mixture into an airtight container and freeze for about</p><p>three hours. This dessert not only provides a burst of energy but also a</p><p>healthy dose of antioxidants, making it a delightful and guilt-free</p><p>indulgence.</p><p>FEED YOUR ESTROBOLOME</p><p>Here’s another impressive yet poorly publicized benefit of eating more</p><p>plants. It’s become common knowledge that our bodies are host to trillions</p><p>of bacteria called the microbiome, chiefly residing in our gastrointestinal</p><p>tract. Scientific research has demonstrated that these gut microbes help</p><p>regulate many aspects of our physiology, including nutrient absorption,</p><p>intestinal strength, and immunity. However, few are aware those same</p><p>microbes also play nice with our precious estrogen.</p><p>Meet the estrobolome, a widely overlooked collection of gut bacteria</p><p>with the unique ability of metabolizing estrogen. Here’s how it works: Once</p><p>estrogen makes its rounds throughout the body, spreading its magic, it heads</p><p>for the intestines, where it’s either reabsorbed into the bloodstream or</p><p>eliminated the same way nutrients are. The estrobolome is in charge of this</p><p>process. These bacteria produce an enzyme called beta-glucuronidase,</p><p>which breaks down estrogen into its active forms, deciding whether to send</p><p>it back in the circulation or pass it out of the system. By making this call,</p><p>the estrobolome keeps things in balance, ensuring that the overall amount of</p><p>estrogen in the body is just right. Moreover, the estrobolome is an expert at</p><p>breaking down complex carbs and putting antioxidants to work, which</p><p>further underscores the connection between estrogen and plant-based foods.</p><p>Taking good care of these friendly bacteria pays off, keeping us all</p><p>healthy campers. A top-drawer gut is associated with a lower risk of</p><p>obesity, heart disease, dementia, depression, cancer, and a gentler</p><p>menopause. The opposite is also true. If you’re already gut savvy, you may</p><p>have heard of dysbiosis—a problem that arises when gut microbes are</p><p>outnumbered by harmful bacteria and knocked out of balance. Dysbiosis</p><p>results in digestive issues and overall inflammation, making our</p><p>estrobolome... estrobummed. As a result, estrogen levels may also be out</p><p>of whack, resulting in jagged levels being released in the bloodstream.</p><p>What causes dysbiosis? While chronic stress and overusing antibiotics</p><p>play their parts, a poor diet is the biggest culprit. Your estrobolome, as well</p><p>as your entire microbiome, goes to town on plants—the more, the merrier.</p><p>When you eat a wide variety of plant-based foods, your microbiome</p><p>receives the bounty of nutrients on which it relies. Avoiding processed</p><p>foods and reducing meat and dairy also seems to help, as people who follow</p><p>diets high in fiber and low in animal fat boast the healthiest microbiomes.</p><p>Consider this: Eating processed foods for as little as two weeks can reduce</p><p>the biodiversity of your microbiome by 40 percent and, at the same time,</p><p>put your estrogen-balancing bacteria in jeopardy and your health with it.</p><p>Our society’s tendency to go on diets low in fiber and high in low-quality</p><p>nutrients is wreaking havoc on us, like it or not. Fortunately, there is a</p><p>foolproof way to restore our microbiome. You guessed it: eating more</p><p>plants mends the mess. To restore your gut bacteria, focus on foods rich in</p><p>prebiotics, probiotics, and the lesser-known bitters:</p><p>Prebiotics are nondigestible carbohydrates, your gut bacteria’s</p><p>favorite menu. Garlic, onions, asparagus, beets, cabbage, leeks, and</p><p>artichokes are fantastic sources, as are legumes like beans, peas, and</p><p>lentils.</p><p>Probiotics are live bacteria that repopulate the microbiome. Find</p><p>these in fermented foods like sauerkraut, kimchi, unsweetened</p><p>yogurt, and brine-fermented pickles. Probiotic supplements can also</p><p>be helpful, especially those containing at least three different strains:</p><p>lactobacillus, rhamnosus, and bifidobacterium.</p><p>Bitters are a group of plants that are defined by exactly what their</p><p>name implies: their bitterness. Bitter herbs like dandelion greens,</p><p>endive, radicchio, and arugula are powerful digestive stimulants that</p><p>love up the microbiome. Toss these veggies with lemon juice or</p><p>vinegar for maximum benefits.</p><p>THE CASE FOR PHYTOESTROGENS</p><p>Estrogen is an ancient hormone that we produce as humans. However, it is</p><p>not unique to us, as many other animals and plants make it, too. Case in</p><p>point, scientists have identified almost 300 plants that produce</p><p>phytoestrogen, or plant-based estrogen, similar in its chemical makeup to</p><p>the estrogen made by our ovaries and with similar functionalities. Now,</p><p>there is some confusion over what phytoestrogens can and can’t do for</p><p>women’s health. Some people believe that phytoestrogens pump up</p><p>estrogen levels, calling them fertility heroes, while others declare them</p><p>villains that render you potentially prone to certain cancers (which is how</p><p>soy got a bad rep). Others still regard phytoestrogens as ineffective or</p><p>useless. The internet weighs in, some sites claiming you shouldn’t consume</p><p>them at all to avoid developing estrogen dominance. I could write a treatise</p><p>on this topic, but I figured you might appreciate the quicker Q&A that</p><p>follows.</p><p>Which Foods Contain Phytoestrogens?</p><p>There are three main types of phytoestrogens:</p><p>Isoflavones are found in soybeans, tofu, tempeh, lima beans,</p><p>chickpeas, and lentils.</p><p>Lignans are found in seeds like flaxseed and sesame; fruits such as</p><p>dried apricots, dates, peaches, and berries; and vegetables like</p><p>garlic, winter squash, and green beans. They are also in grains such</p><p>as wheat and rye and nuts like pistachios and almonds.</p><p>Coumestans are found in sprouting seeds such as alfalfa.</p><p>Do Phytoestrogens Have Any Effects on the Human Body?</p><p>Phytoestrogens have a molecular structure similar to that of the estrogen</p><p>produced by our ovaries, and they bind to the same receptors. As such, they</p><p>function similarly to our own estrogen but are weaker. Their ability to latch</p><p>on to estrogen receptors is only a thousandth</p><p>of the strength of estradiol. As</p><p>a result, their effects are much milder, unless you combine them together in</p><p>specific amounts. In this case, their activity is amplified. Nonetheless, these</p><p>foods have an effect only when consumed consistently. (In case you’re</p><p>wondering, no, phytoestrogens won’t stop your body from making its own</p><p>estrogen.)</p><p>Are Phytoestrogens Dangerous?</p><p>On the contrary, these compounds show a protective role in hormonal</p><p>health. Phytoestrogens are peculiar compounds. They carry out both</p><p>estrogenic and anti-estrogenic activities and are selective in their</p><p>application. In fact, they are very similar to the selective estrogen receptor</p><p>modulators, or SERMs, used for cancer treatment. While the exact</p><p>mechanisms of their action are still under investigation, phytoestrogens tend</p><p>to adjust to the estrogen level in your bloodstream and may be in cahoots</p><p>with the estrobolome in your gut. When estrogen levels are high enough,</p><p>phytoestrogens may gently block estrogen receptors, protecting you from</p><p>excess exposure. When estrogen levels are low, phytoestrogens may step in</p><p>to bolster those levels, though in a much milder way than your own</p><p>estrogen.</p><p>Can Phytoestrogens, Soy in Particular, Cause Cancer?</p><p>Soy is one of the most controversial foods on the planet. You will find it</p><p>promoted as a superfood one minute and listed as a cancer-inducing poison</p><p>the next. However, Asian women eat soy regularly and are four times less</p><p>likely to get breast cancer than their Western counterparts. While genetic</p><p>and cultural factors also play a role, many studies have shown a lower rate</p><p>of breast cancer in populations consuming soy as a regular part of the diet.</p><p>These women are less likely to suffer from hot flashes, osteoporosis, and</p><p>heart disease, too. At the very least, that’s an indication that soy is unlikely</p><p>to be dangerous.</p><p>Overall, there is no evidence that soy or the phytoestrogens it carries</p><p>cause cancer. For many years, professional societies recommended avoiding</p><p>soy and other estrogenic plants. However, more rigorous research led both</p><p>the American Institute for Cancer Research and the American Cancer</p><p>Society to revise their position in 2013. Today, soy is considered safe for</p><p>women, including patients with breast cancer. Extensive research has shown</p><p>that soy does not increase the odds of breast tumor recurrence and, in some</p><p>cases, may even reduce mortality. Additionally, soy has no adverse effects</p><p>on endometrial, ovarian, or other cancers.</p><p>One caveat: People who are allergic to soy should avoid both soy and its</p><p>derivatives. Also, the type of soy you’re eating matters. The traditional soy</p><p>products consumed in Asia are clean, unprocessed, and often fermented,</p><p>which most of our soy is not. In the Western world, most soy products are</p><p>made of genetically modified soybeans rife with pesticides and</p><p>preservatives. Worse yet, processed soybean oil, soy lecithin, and isolated</p><p>soy protein lace everything from packaged foods and breakfast cereals to</p><p>lattes and infant formulas—and have nothing to do with good health. Stay</p><p>clear of considering these versions of soy as anything resembling a</p><p>superfood. If you are interested in eating soy to support a healthy</p><p>menopause, seek organic and fermented soy, such as fresh edamame, miso,</p><p>and tempeh.</p><p>Are There Benefits to Eating Phytoestrogens?</p><p>While the findings are not always consistent, clinical trials indicate that</p><p>eating soy and, more generally, isoflavones potentially lessens the number</p><p>of hot flashes. In a recent study published by the North American</p><p>Menopause Society, a plant-based diet rich in soy reduced moderate to</p><p>severe hot flashes by as much as 84 percent, lowering a five-a-day</p><p>occurrence to fewer than once a day. In this study, postmenopausal women</p><p>experiencing hot flashes were randomly assigned to a plant-based diet,</p><p>including half a cup of cooked soybeans added to a salad or soup each day.</p><p>The remaining participants made up the control group and were given no</p><p>dietary changes. During the twelve-week study, over half of participants on</p><p>the plant-based, soy-enriched diet became free of hot flashes. Most</p><p>participants also reported an improved quality of life, mood, libido, and</p><p>overall energy. Although this was a small study, the results are impressive,</p><p>meriting consideration.</p><p>FOCUS ON ESSENTIAL FATS</p><p>Just like carbohydrates, not all fat is created equal. While for many years,</p><p>people were advised to reduce the overall quantity of fat in the diet, it turns</p><p>out that the type of fat is more important than the actual amount being</p><p>consumed. There are three main kinds of fat, each with its distinct effects:</p><p>Unsaturated fat can be monounsaturated, as in olive oil and</p><p>avocado) or polyunsaturated, found in fish, shellfish, and various</p><p>nuts and seeds, as well as some vegetables, grains, and legumes.</p><p>Saturated fat is abundant in dairy, meat, and certain oils (like</p><p>coconut oil).</p><p>Trans-unsaturated fats, or trans fats, are produced when unsaturated</p><p>oils are processed using a procedure called hydrogenation. This</p><p>makes them become similar to saturated fats, achieving a longer</p><p>shelf life. These trans fats typically lurk in processed foods and are</p><p>the worst fat you can eat, so much so that they’re banned in many</p><p>countries. We’ll discuss them later in “Foods to Avoid.”</p><p>Omega-3s Are the Real Stars</p><p>Much women-based research reveals that polyunsaturated fat supports</p><p>women’s health, showing a reduced risk of heart disease, obesity, diabetes,</p><p>and dementia. These female-friendly fats come in different varieties, the</p><p>most common being omega-3 and omega-6 fatty acids. Omega-3s are</p><p>particularly helpful thanks to their anti-inflammatory and antioxidant</p><p>effects. In contrast, women who don’t consume enough omega-3s may</p><p>experience more menstrual pain, fertility issues, and postpartum as well as</p><p>menopausal depression.</p><p>There are different types of omega-3s:</p><p>ALA, or alpha-linolenic acid, found exclusively in plant foods.</p><p>EPA, or eicosapentaenoic acid, and DHA, or docosahexaenoic acid,</p><p>found mainly in fish and seafood, but also seaweed and algae.</p><p>ALA, EPA, and DHA are all referred to as essential fats because the body</p><p>cannot produce them on its own and you can obtain them only by eating the</p><p>proper foods. However, ALA is the only omega-3 that’s literally essential.</p><p>That’s because the body can use ALA to make the other two, EPA and</p><p>DHA. However, quite a bit of ALA is lost in the process, so it’s important</p><p>to be mindful of this.</p><p>Most dietary guidelines for women recommend getting at least 1,100 mg</p><p>of omega-3s every day. This dosage is easily achieved, for example, by</p><p>using flaxseed (linseed) oil. This beautiful golden oil is made from</p><p>flaxseeds that have been ground and pressed to release their natural oil. Just</p><p>one tablespoon (15 ml) contains an impressive 7,200 mg of omega-3 ALA,</p><p>so you’re set for the day. Other excellent alternatives include ground</p><p>flaxseed, hempseed, walnuts, and almonds. Olives, olive oil, avocados, and</p><p>soybeans are also excellent sources, as are broccoli, sweet peas, and many</p><p>leafy greens. Algae and seaweed are important sources of omega-3s for</p><p>people on vegan or vegetarian diets, or anyone who doesn’t eat fish, as they</p><p>are one of the few plant foods containing preassembled DHA and EPA.</p><p>Monounsaturated Fat Makes Your Heart Happy</p><p>Monounsaturated fat is known for its protective effects on heart health. Nuts</p><p>like almonds, pistachios, Brazil nuts, cashews, and hazelnuts are high in</p><p>monounsaturated fat, as are fatty fruits like avocados and olives, and some</p><p>seeds like sesame and sunflower. In a study of over 86,000 women, those</p><p>who frequently consumed nuts had a much lower risk of heart disease and</p><p>stroke. A handful of nuts or seeds (about an ounce) once a week, with the</p><p>peel still on, delivers targeted results. Avoid blanched, flavored, salted,</p><p>sweetened, or seasoned nuts and seeds. This snack is often mistaken for</p><p>healthy, but it’s processed and laden with chemicals and sugars.</p><p>Saturated Fat Is Best from Plant-Based Sources</p><p>Saturated fat comes from both animal</p><p>sources, such as meat and dairy, and</p><p>plant-based sources, like coconuts, avocados, and nuts, such as cashews and</p><p>macadamia nuts. There is increasing evidence that saturated vegetable fat</p><p>supports women’s health through its beneficial effects on our hormones,</p><p>while saturated fat from animal sources does not show the same result. A</p><p>possible explanation is that vegetable fat seems to have a gentler impact on</p><p>blood lipid levels than animal fat. For example, in randomized clinical</p><p>trials, dairy butter increased LDL cholesterol significantly, whereas olive oil</p><p>and coconut oil did not. To be clear, we are referring to vegetable fat</p><p>derived from whole foods, and not from products like margarine or</p><p>processed plant-based spreads.</p><p>Too much animal fat has also been linked to an increased risk of</p><p>hormone-related cancers. In the Nurses’ Health Study, women who</p><p>consumed more animal products, especially red meat and high-fat dairy, had</p><p>three times the risk of developing breast cancer compared with those who</p><p>consumed fewer of these foods. This could be because animal fat, contrary</p><p>to fiber, has negative effects on the estrogen-balancing SHBG molecule.</p><p>Possibly as a result, replacing some animal fat with vegetable fat, especially</p><p>oils high in antioxidants like extra-virgin olive oil and flaxseed oil, has been</p><p>linked to a reduced risk of breast cancer, heart disease, and diabetes in</p><p>women.</p><p>Cholesterol Is Important for Hormonal Health</p><p>Cholesterol often gets a bad rap, but in truth, this type of fat plays a crucial</p><p>role in many bodily functions, from forming healthy cell walls to making</p><p>enough estrogen. However, too much of certain types of cholesterol can get</p><p>you in trouble. There are different kinds of cholesterol:</p><p>HDL (high-density lipoprotein), aka “good” cholesterol.</p><p>LDL (low-density lipoprotein) and VLDL (very low-density</p><p>lipoprotein), which are considered “bad” cholesterol. High levels of</p><p>bad cholesterol have been linked to plaque buildup in the arteries</p><p>and other heart issues, too.</p><p>Measuring your cholesterol levels is an effective way to determine your</p><p>risk of heart disease and stroke. There are two ways to do this. One way is</p><p>to measure your total cholesterol. Typically, you want this number to be</p><p>below 200. An even better way is to calculate your cholesterol ratio. The</p><p>latter will give you a breakdown of your good vs. bad cholesterol,</p><p>delivering a clearer picture of your health. If your total cholesterol is 200</p><p>and your HDL cholesterol is 50, your ratio is 4. A ratio lower than 4.5 is</p><p>considered good, but 2 or 3 is best.</p><p>If your cholesterol is above limits, it’s important to lower it. Cholesterol</p><p>comes from two sources: Some 80 percent or so is made by the liver, while</p><p>the rest comes from the foods you eat. Traditionally, doctors advised their</p><p>patients to reduce their consumption of cholesterol-rich foods, especially</p><p>eggs, to lower their cholesterol levels. However, newer research has shown</p><p>that cholesterol from food doesn’t raise the cholesterol in the blood nearly</p><p>as much as other types of fats do, chiefly trans fats and saturated fats from</p><p>animal sources, so that’s another reason to avoid or reduce those other fats.</p><p>Eating more plants is also helpful in this regard because plants simply don’t</p><p>contain any cholesterol to start with. Some multitasking plant-based foods</p><p>can also help lower your bad LDL while at the same time promoting the</p><p>production of good HDL. These include avocados, lemons, oranges, beans,</p><p>legumes, and whole grains like oats and brown rice. Cooking and seasoning</p><p>with fruit oils (such as olive and coconut oils) rather than butter or animal</p><p>fats also fit the bill.</p><p>LEAN PROTEIN</p><p>The word protein often conjures up images of bodybuilders and dumbbells.</p><p>But this macronutrient is so much more than that. In fact, protein is a</p><p>critical building block that our bodies use in a multitude of ways, from</p><p>making new cells and repairing damaged ones to being a component of</p><p>many hormones. Protein also keeps our bones sturdy by maintaining a</p><p>process known as bone remodeling, thus reducing the risk of osteoporosis.</p><p>Further, a diet including adequate amounts of protein combined with regular</p><p>exercise works to regenerate muscle mass. So eating adequate protein</p><p>during menopause can help keep our metabolism running smoothly while</p><p>supporting a healthy weight.</p><p>As with the carbs and fats, protein comes in many types. The one we</p><p>want to prioritize is high-quality lean protein. Lean protein is typically</p><p>lower in saturated fat and therefore calories—hence the word lean. It is</p><p>found in a wide variety of foods of animal origin, such as fish, poultry, and</p><p>lean meat cuts, as well as a variety of foods of plant origin, which we’ll</p><p>discuss in greater detail below. First, let’s address the common concern that</p><p>diets rich in plant foods may lack sufficient protein.</p><p>Protein is made up of chains of molecules known as amino acids. There</p><p>are twenty amino acids found in nature that your body uses to build protein.</p><p>Out of these, nine are considered essential. Remember, essential means that</p><p>your body cannot produce these nutrients on its own, so you need to eat</p><p>them in your diet. Protein of animal origin contains all nine essential amino</p><p>acids, typically in sufficient amounts per portion. As such, it’s referred to as</p><p>complete protein. Plants also contain these essential amino acids, though</p><p>typically have a limited amount of at least one of them. For instance,</p><p>vegetables and legumes tend to contain low amounts of cysteine and</p><p>methionine. Grains, nuts, and seeds tend to be lacking in lysine. Because of</p><p>this, many people refer to plant foods as incomplete protein. However, as</p><p>long as you eat a variety of plant-based foods, you can easily tally up</p><p>sufficient amounts of essential amino acids by combining different plant</p><p>foods in the same meal. The renowned rice and beans combo is a good</p><p>example. Besides, some plant foods actually contain more protein per</p><p>portion than some animal products. For example, green peas, which are</p><p>actually part of the bean family. Believe it or not, a cup of these yummy</p><p>peas has more protein than a cup of milk. For another honorable mention,</p><p>spirulina (a type of blue-green algae) contains 8 grams of complete protein</p><p>per just 2 tablespoons of the green stuff. Nutritional yeast, a common vegan</p><p>cheese substitute, also delivers 8 grams of complete protein in just half a</p><p>tablespoon. I am not suggesting you consume these foods if you don’t enjoy</p><p>them. Rather, the aim is to clarify that plant-based foods are viable sources</p><p>of protein. Returning to our starting point, if you eat animal foods, fish,</p><p>eggs, and poultry are readily found sources of lean protein. Plant foods that</p><p>contain a good amount of lean protein per serving include:</p><p>seitan (25 grams of protein per 3.5 ounces, or 100 grams)</p><p>tofu, tempeh, and edamame (12–20 grams per 3.5 ounces, or 100</p><p>grams)</p><p>lentils (18 grams per cooked cup, or 170 grams)</p><p>beans (15 grams per cooked cup)</p><p>spelt and teff (10–11 grams per cooked cup, or 250 grams), making</p><p>these ancient grains higher in protein than quinoa</p><p>quinoa (8–9 grams per cooked cup, or 185 grams)</p><p>green peas (9 grams per cooked cup, or 160 grams)</p><p>spirulina (8 grams of complete protein per 2 tablespoons)</p><p>hempseed (9 grams per 3 tablespoons)</p><p>oats (5 grams of protein per ½ cup of dry oats)</p><p>IRON</p><p>Iron is another concern that often pops up when considering a plant-focused</p><p>diet. Plant foods contain a type of iron called non-heme iron, which is</p><p>generally less bioavailable (less easily absorbed by the body) than the iron</p><p>found in meat, called heme iron. So the problem is not simply the quantity</p><p>of iron present in the foods but our bodies’ ability to absorb it. In fact, many</p><p>plant foods are perfectly good sources of iron, including oats, soybeans,</p><p>legumes, and leafy greens. Some of these foods contain even more iron than</p><p>meat. For example, 3 cups of spinach or 1 cup of lentils have more iron than</p><p>an 8-ounce steak. However, their iron is not as promptly put to good use.</p><p>One way to increase the absorption of plant</p><p>iron is to combine these foods</p><p>with other foods rich in vitamin C. For example, sprinkle some berries on</p><p>your oats or lemon juice into your salads and, voilà! mission accomplished.</p><p>VITAMIN B12</p><p>Vitamin B12 is the only vitamin you can’t obtain from plants. In this case,</p><p>eating a flexible diet that contains B12 or taking a supplement is in order.</p><p>That said, even with a proper diet, many people over the age of fifty may</p><p>need vitamin B12 supplements to make sure they’re hitting the</p><p>recommended intake. According to the National Institutes of Health (NIH),</p><p>up to 43 percent of older adults suffer from a B12 deficiency. More on this</p><p>in chapter 15.</p><p>CALCIUM-RICH FOODS</p><p>It is no big secret that we need more calcium and vitamin D to support bone</p><p>health as we age. But contrary to popular belief, you don’t need dairy to get</p><p>calcium; many plant-based foods are just as good. Various vegetables pack</p><p>a punch, like spinach, turnips, kale, bok choy, and mustard greens, as well</p><p>as legumes like soybeans, tofu, beans, and peas. Seeds can be good sources,</p><p>too. Consider this: A glass of whole milk contains about 280 milligrams of</p><p>calcium, as does 1 cup of cooked spinach or 2 tablespoons of tahini.</p><p>Another easy way to swap out animal-based for plant-based calcium is by</p><p>drinking plant-based milk; many of these beverages have roughly the same</p><p>amount of calcium as cow-dairy.</p><p>Vitamin D is difficult to obtain from diet alone, no matter what you eat.</p><p>It’s not called the “sunshine vitamin” for nothing. Our bodies manufacture</p><p>vitamin D from cholesterol when our skin is exposed to the sun. Get your</p><p>vitamin D levels checked, and if they’re low, you’ve got a doc’s note to</p><p>book that tropical vacation you’ve always wanted! Otherwise, stock up on</p><p>foods fortified with vitamin D or take a supplement (discussed in the next</p><p>chapter).</p><p>A final note on dairy products. There is a great deal of conjecture that the</p><p>hormonal residues in dairy from growth factors fed to dairy cows may</p><p>contribute to tumor growth in humans, though this has not been thoroughly</p><p>researched. While the jury is still out on the role of dairy products on breast</p><p>cancer, focusing on organic dairy free of growth hormone is important</p><p>should you choose to consume it. Goat or sheep milk is also more easily</p><p>digestible than cow’s milk.</p><p>MELATONIN FOR SLEEP SUPPORT</p><p>Believe it or not, some foods contain melatonin, the sleep-cuing hormone.</p><p>Pistachios in particular are the most melatonin-rich food on the planet.</p><p>Eating a whole handful of pistachios is equivalent to popping a melatonin</p><p>supplement before bed. This shell-snapping snack is also a great source of</p><p>fiber, vitamin B6, and some essential amino acids. Melatonin can also be</p><p>found in some mushrooms, especially the portobello variety, as well as</p><p>various sprouted seeds and lentils. Wheat, barley, and oats are also good</p><p>sources, as are grapes, dark cherries, and strawberries. Imagine a dinner</p><p>salad garnished with sprouted lentils, roasted mushrooms, and pistachios—</p><p>with a strawberry sorbet for dessert. Your estrobolome will love you for it,</p><p>and perhaps you won’t have to count sheep that night.</p><p>FOODS TO AVOID</p><p>Whenever someone asks me for my number one diet tip for brain health, I</p><p>always, without fail, give the same answer: do not eat processed foods.</p><p>People in the United States, Canada, and the UK consume almost 50</p><p>percent of their daily calories from processed foods, many of which are not</p><p>only processed but ultra-processed. That means nearly half of the food we</p><p>eat daily has been significantly modified from its original state, with the</p><p>most detrimental versions of salt, sugars, fats, additives, preservatives, and</p><p>artificial colors and flavors. Ultra-processed foods undergo multiple</p><p>processes (extrusion, molding, milling, and so forth), contain long lists of</p><p>added chemicals, and are highly manipulated. Examples are commercial</p><p>white bread loaves, packaged pastries, snacks, and all industrialized</p><p>confectionery and desserts; commercially fried and prepared foods; and all</p><p>fast food, including but not limited to soft drinks, soda, and sugar-</p><p>sweetened beverages; processed meat and cold cuts; processed cheeses;</p><p>margarine, shortening, and lard; instant noodles and soups; frozen or shelf-</p><p>stable meals; most bottled condiments, spreads, and creamers; chips,</p><p>chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups,</p><p>chicken nuggets, burgers, hot dogs, and so forth (the list, unfortunately,</p><p>could fill its own book). Depending on where you’re shopping,</p><p>supermarkets may carry more processed and ultra-processed foods than</p><p>minimally or unprocessed foods. In chapter 17, we’ll go over specific tips</p><p>to recognize and avoid the toxic ingredients in these foods.</p><p>For now, suffice it to say that the more ultra-processed foods you eat, the</p><p>poorer the overall nutritional quality of your diet, and the poorer your</p><p>health. The World Cancer Research Fund and the American Institute for</p><p>Cancer Research state that ultra-processed foods may well cause one-third</p><p>of all the world’s cancers. Processed foods, such as salty snacks and</p><p>processed meat in particular, have also been identified as the culprit behind</p><p>an estimated 45 percent of deaths from heart disease, stroke, and diabetes.</p><p>After evaluating over 800 studies, the World Health Organization (WHO)</p><p>concluded that processed meat is also carcinogenic, much like tobacco</p><p>smoking and asbestos. Processed meat is meat that is salted, cured,</p><p>fermented, smoked, or otherwise processed to enhance flavor and improve</p><p>preservation, such as most lunch meats sold at your deli counter,</p><p>supermarket, or sandwich shop. These meats include commercial boiled</p><p>ham, roast beef, turkey, chicken, bologna, and hot dogs.</p><p>CUT DOWN ON ALCOHOL, CAFFEINE, AND SPICY FOODS</p><p>Navigating the culinary landscape of menopause can be quite the adventure.</p><p>It’s no secret that certain foods—chiefly spicy foods, alcohol, and caffeine</p><p>in coffee, tea, or energy drinks—have a knack for aggravating those pesky</p><p>symptoms. As every woman is different, it’s important to play detective</p><p>with your taste buds and notice whether these foods trigger or worsen any</p><p>symptoms you have, and experiment with reducing or avoiding these foods</p><p>and drinks.</p><p>Generally, spicy foods can contribute to the sensation of heat rising in</p><p>your body or make your hot flashes perform an encore. Alcohol is also</p><p>famous for worsening hot flashes. While many think a drink may help them</p><p>fall asleep, it may be the culprit behind your midnight wake-up call.</p><p>Additionally, while red wine can still have its cardio-protective charms in a</p><p>5-ounce glass per day, moderation is key to keep the breast cancer risk at</p><p>bay.</p><p>Now, let’s talk caffeine. As much as many of us adore the morning java</p><p>jolt, it’s worth noting that caffeine can be a double troublemaker—it can</p><p>make hot flashes worse while also having negative effects on sleep.</p><p>Caffeine can take up to twelve hours to leave your system, so why not limit</p><p>yourself to one cup per day, savored before noon? Here’s an interesting</p><p>twist: contrary to popular belief, freshly brewed espresso can actually be</p><p>gentler on your menopausal woes compared to an Americano. The shorter</p><p>extraction time of espresso means it contains less caffeine than its diluted</p><p>counterpart. You can thank me later!</p><p>SERIOUSLY, DRINK WATER</p><p>When it comes to what drink is the healthiest, the best advice I can give you</p><p>is to drink water. Given how critical water is for the brain, I dedicated an</p><p>entire chapter to this remarkable nutrient in Brain Food. Moreover, proper</p><p>hydration is just as crucial for hormonal health and menopause. Here’s a</p><p>brief overview:</p><p>Even mild dehydration can trigger dizziness, confusion, fatigue, and</p><p>big-time brain fog, at any age. Keeping hydrated reduces the risk of</p><p>all these symptoms, which are common in menopause.</p><p>Staying hydrated can help support the body’s hormone production</p><p>and balance.</p><p>Proper hydration helps to regulate body temperature, helping to</p><p>lessen hot flashes.</p><p>Proper hydration is also key to vaginal lubrication, which comes in</p><p>handy after menopause.</p><p>Drinking water aids in digestion, circulation, and elimination,</p><p>ensuring the body can function optimally and fight inflammation.</p><p>Hydration is crucial for maintaining healthy joints, reducing</p><p>discomfort and stiffness.</p><p>Drinking water helps keep the skin and hair hydrated, promoting</p><p>elasticity and reducing dryness.</p><p>This may sound weird, but the type and quality of water actually matters.</p><p>See, water isn’t just water. Our bodies, brains, and hormonal systems don’t</p><p>just need something wet. We specifically need natural water, complete with</p><p>its native minerals, salts, and electrolytes. Drinking spring water, mineral</p><p>water, or filtered tap water that retains its electrolytes is the best way to</p><p>support hydration. Purified water, club soda, and seltzer don’t cut it, since</p><p>they don’t contain any of the hydrating nutrients that actual water does.</p><p>Soda (Coke or other similar beverages) is not water in the first place, and</p><p>can do a number on your ovaries, as it’s associated with an increased risk of</p><p>ovulatory infertility.</p><p>Another smart way to support hydration is to eat your water. An ounce of</p><p>water-rich fruits or vegetables is equivalent to an ounce of water trapped in</p><p>a web of nutrients—fiber, phytonutrients, and antioxidants. Think radishes,</p><p>watermelon, cucumbers, strawberries, tomatoes, watercress, apples, celery,</p><p>melons, lettuce, peaches, and cauliflower—these fruits and vegetables are</p><p>quick to quench!</p><p>EAT MINDFULLY</p><p>The obesity epidemic has spawned an entire industry of weight-loss</p><p>programs. Currently getting a lot of attention is intermittent fasting, which</p><p>broadly involves alternating intervals of eating and not eating, or eating</p><p>fewer calories at specific times. This may help shed pounds and stabilize</p><p>weight more efficiently than other types of diets, while also reducing</p><p>inflammation and risk of heart disease. As a result, intermittent fasting is</p><p>often also recommended for menopausal women.</p><p>Here’s my take on this. First, while there is rigorous research behind</p><p>time-restricted feeding in laboratory animals, scientific evidence for the</p><p>health benefits of intermittent fasting in humans is more limited than you</p><p>may think. Research studies in people have small sample sizes and focus on</p><p>very specific populations, mainly overweight individuals with or without</p><p>diabetes or well-trained athletes. Second, there are several trendy versions</p><p>of this practice that have nothing to do with science. Instead, they come out</p><p>of people’s personal opinions about what one should eat and not eat to</p><p>break the fast or throughout the rest of the day. Many of these plans border</p><p>on nonsense. Just as important, research on intermittent fasting in women is</p><p>still relatively limited compared to studies involving men. Even less work</p><p>has been done concerning this practice during menopause, not even in</p><p>animals, so better be wary of the headlines.</p><p>In many parts of the world, there is a form of “fasting” that’s been around</p><p>for centuries, if not millennia, and is both doable and sensible. It’s</p><p>called . . . sleeping. The world’s healthiest dietary patterns all involve</p><p>having a light dinner early in the evening, and then refraining from eating</p><p>overnight, which is when you should be winding down and sleeping</p><p>instead. Once you get up the day after, usually ten to twelve hours later, you</p><p>have a proper breakfast and are ready to go on with your day.</p><p>In the end, the only successful diets—whatever the goal—involve</p><p>sustainable and long-lasting changes in eating habits that are conducive to</p><p>health. I’d argue that how we approach our food is just as important, if not</p><p>more so, than a specific eating schedule. Making smart food choices and</p><p>eating mindfully throughout the day are both key in this respect. Mindful</p><p>eating stems from the broader philosophy of mindfulness, a widespread</p><p>centuries-old practice in many cultures and religions. Eating mindfully</p><p>means using your physical and emotional senses to experience and enjoy</p><p>your food choices. This focus encourages options that are both satisfying</p><p>and nourishing. Most of us are busy, rushed, and poised over our keyboards</p><p>as we gobble our meals. What if we slowed down and paid better attention?</p><p>When we do, we know when we’re genuinely physically hungry as opposed</p><p>to having eaten enough. This also helps to alleviate digestive upset like</p><p>bloating and heartburn, your body’s way of avenging that spicy calzone you</p><p>inhaled in seventeen seconds flat. As most people in Western countries tend</p><p>to overeat to start with, paying more attention to the moment-to-moment</p><p>experience of eating can help improve the quality of your diet, too. This</p><p>consciousness in turn may allow us to manage cravings more efficiently,</p><p>reduce stress-eating, and lose weight when necessary.</p><p>In conclusion, when it comes to dietary choices during menopause, the</p><p>key is to focus on a balanced, nutritious, and sustainable approach. Instead</p><p>of falling for fad diets or restrictive eating patterns, prioritize consuming</p><p>whole foods, proper hydration, and plenty of plants. Incorporating a variety</p><p>of fruits, vegetables, whole grains, lean protein, and healthy fats is key to</p><p>providing the necessary nutrients to support your hormonal health and</p><p>overall well-being. While it’s important to be mindful of portion sizes and</p><p>caloric intake, it’s equally important to listen to your body’s hunger and</p><p>fullness cues. Avoid overly strict or rigid approaches that may lead to</p><p>feelings of deprivation or disrupt a healthy relationship with food.</p><p>Remember, there is no one-size-fits-all approach to nutrition during</p><p>menopause. By embracing a sensible approach to eating, you can nourish</p><p>your body, brain, and hormones throughout the menopausal transition and</p><p>beyond, keeping your inner thermostat in check and your zest for life</p><p>vibrant.</p><p>15</p><p>Supplements and Botanicals</p><p>THE POWER OF PLANTS</p><p>While HRT has long been a standard treatment for menopausal symptoms,</p><p>concerns about its risks have made for a history of fits and starts. These</p><p>stumbles, combined with a renaissance of interest in herbal remedies and</p><p>supplements for hormonal health, produced a dramatic increase in so-called</p><p>natural solutions. As a result, up to half of all women in industrialized</p><p>countries now rely on plant-based supplements for menopause.</p><p>Generally, supplements can be divided into botanicals (like soy extracts,</p><p>black cohosh, and ginseng) and non-botanicals (such as vitamins and</p><p>minerals). Botanicals are often divided into having and not having</p><p>estrogenic effects, which makes the latter more suitable for women with</p><p>concerns about breast cancer. From ancient times to the present day, every</p><p>culture around the world has employed a variety of plants as the basis for</p><p>their medicinal needs. Several types of herbs have been used to manage hot</p><p>flashes, including black cohosh, dong quai, evening primrose, ginseng,</p><p>flaxseed, red clover, St. John’s wort, and wild yam. Other botanicals, such</p><p>as maca and horny goat weed, are used to boost sex drive, while lemon</p><p>balm, valerian, and passionflower are often recommended for the insomnia,</p><p>anxiety, and fatigue that can accompany the transition. However, while</p><p>some of these preparations are supported by scientific evidence, others are</p><p>not. For example, wild yam creams used to soothe hot flashes show no</p><p>effect in clinical studies, whereas phytoestrogen supplements (a more</p><p>concentrated, potent version of the phytoestrogens present in our foods)</p><p>figure prominently as having positive effects. Ideally, one would want to try</p><p>out the latter and avoid the former, so check out my notes to each</p><p>supplement.</p><p>A word of caution before we begin. Many people attempt to employ</p><p>supplements as shortcuts, sidestepping dietary demands, and are upset when</p><p>supplements fail to achieve their goals. So keep in mind that nutritional</p><p>supplements are complementary in nature and cannot replace a healthy diet</p><p>or lifestyle.</p><p>Another consideration is that supplements are not subject to the scrutiny</p><p>of federal regulatory bodies like the FDA. Unlike prescription drugs,</p><p>2</p><p>Busting the Bias Against Women</p><p>and Menopause</p><p>SEXISM AND NEURO-SEXISM</p><p>This book is a neuroscientist’s take on the ups and downs of menopause.</p><p>Before we reveal the future of the field, however, it’s useful (albeit a bit</p><p>dismaying) to review the cultural and clinical perspectives on menopause to</p><p>date. I warn you that retracing some key sociohistorical steps on the topic</p><p>might leave you feeling gloomy at first. After all, the combo of culture and</p><p>conventional medicine is the reason we equate menopause with “ovarian</p><p>failure,” “ovarian dysfunction,” “estrogen depletion,” and another slew of</p><p>negative outcomes. But stick with me; I promise that if we draw from</p><p>modern science, there’s a very different and more balanced story to tell.</p><p>From a cultural perspective, however, the outlook is unequivocally dim.</p><p>If we dig a little deeper, it’s clear that many of the demeaning stereotypes</p><p>around menopause originate from a broader negative understanding of</p><p>women[*] as the “weaker sex.” If we start with the age-old sense that</p><p>women are physically more fragile than men, this reference is also applied</p><p>to our brains and intellect in the form of what we now call neuro-sexism—</p><p>the myth that women’s brains are inferior to men’s brains. So before we can</p><p>even address the complexity of medical frameworks for menopause, we</p><p>need to address the complexity of the same frameworks for women as a</p><p>whole.</p><p>However astoundingly flawed the doctrine of female inferiority may be,</p><p>it’s nothing short of the backbone of modern science. According to Charles</p><p>Darwin, the father of modern biology, “a man attains a higher eminence, in</p><p>whatever he takes up, than can women—whether requiring deep thought,</p><p>reason, or imagination, or merely the use of the senses and hands.” This</p><p>theory gathered momentum and proliferated unchallenged throughout the</p><p>nineteenth century, when male scientists made an “impressive discovery.”</p><p>They realized not only that women’s heads were anatomically smaller than</p><p>men’s but that women’s brains weighed less than men’s as well. This was</p><p>an era in which the biological premise that “bigger is better” reigned</p><p>supreme. Therefore, a woman’s slender brain was conveniently interpreted</p><p>as a sign of lack of intelligence and mental inferiority. The pundits of the</p><p>day were quick to correlate that with a lack of aptitude for a variety of</p><p>tasks. For example, George J. Romanes, a leading evolutionary biologist</p><p>and physiologist of the time, went on to say this: “Seeing that the average</p><p>brain-weight of women is about five ounces less than that of men, on</p><p>merely anatomical ground we should be prepared to expect a marked</p><p>inferiority of intellectual power in the former.” These assumptions were by</p><p>no means unique, as most intellectuals back then were perfectly</p><p>comfortable embracing an interpretation that suited the status quo. Those</p><p>“missing five ounces” of women’s brains were thus used to justify the</p><p>difference in the social status between men and women, cementing the</p><p>denial of women’s access to higher education or to other rights that might</p><p>have rendered them independent.</p><p>I’m going to go out on a limb here and guess that the following goes</p><p>without saying: the fact that, on average, men’s bodies are larger and</p><p>heavier than women’s might have made the observation that their heads</p><p>were more or less made to match a no-brainer (pun intended). If one has a</p><p>bigger body, the skull and the brain within should be bigger as well. In fact,</p><p>once head size is taken into account, the fabled brain-weight difference</p><p>disappears into the thin air whence it came.</p><p>Just the same, for centuries, women’s brains continued to be weighed and</p><p>found wanting, keeping women out of universities and prestigious jobs.</p><p>Eventually, female scientists and human rights activists joined forces to</p><p>denounce how such biased interpretations were nothing more than political</p><p>weaponry subverting women’s efforts to attain equity and equality. Thanks</p><p>to their efforts, the brain-weight intelligence theory was fully debunked in</p><p>the early twentieth century. The later advent of brain imaging fostered</p><p>further progress in dispelling many of the base assumptions behind neuro-</p><p>sexism, leveling the playing field once and for all.</p><p>Or has it?</p><p>Today, while overtly sexist statements no longer have a place within the</p><p>scientific community, many argue that neuro-sexism is still alive and</p><p>kicking. The thing is, in many respects women’s brains do differ from</p><p>men’s. We’ll talk more about this in just a moment. For now, I want to point</p><p>out that disparities between the genders are too seldom used to modernize</p><p>medical care, and far too often used to reinforce demeaning gender</p><p>stereotypes instead. Consciously or not, we are coerced into gender roles</p><p>from birth, further fed by pop science claims about how our “Venus/Mars”</p><p>behaviors differ due to our brains. It may start with the age-old tradition of</p><p>accessorizing our infants in pink and blue, but it ends with the propagation</p><p>of rigid, derogatory biases that relentlessly cast women as the lesser gender.</p><p>As it now stands, we face a triple challenge: sexism, ageism, and</p><p>menopause-ism. From the moment we are born, the message from our</p><p>society is that we are lesser as women, if for no other reason than the fact</p><p>that men are bigger and stronger. But these baseline beliefs proliferate in</p><p>ways both subtle and not as we traverse the playground, the classroom, and</p><p>the workplace, culminating in middle age. In this timeline, menopause is</p><p>the final blow. After women endure decades of messaging that undermines</p><p>them, here it is yet again, another fundamental female physiological process</p><p>reduced to evidence for weakness and disease. Viewed through a dark</p><p>patriarchal lens, in addition to the widely held belief that a woman’s age</p><p>renders her less attractive, the loss of utility in bearing children is an</p><p>additional unwelcome cultural tax—one that only adds fuel to the fire of</p><p>inferiority, physically, mentally, personally, and even professionally.</p><p>While there is a shortage of reliable science regarding menopause, there</p><p>is certainly no lack of misleading claims or even misogyny surrounding this</p><p>topic. In popular culture, menopausal women have often been portrayed</p><p>through a distressing lens of erratic moods and explosive rages. We’re all</p><p>too familiar with the stereotype of the belligerent menopausal woman,</p><p>tormented by hot flashes and mood swings, depicted as causing turmoil for</p><p>her unfortunate and exasperated husband. This view is nothing new. It is</p><p>deeply rooted in centuries, even millennia, of deep-seated patriarchal</p><p>mistrust of female bodies. Ready for this?</p><p>MENOPAUSE AND THE ANTI-MENOPAUSE MOVEMENT</p><p>The first scientific references to menopause originate around the year 350</p><p>BC, when Aristotle first observed that women would stop having menstrual</p><p>discharge sometime between the ages of forty and fifty. However, given that</p><p>lifespans were shorter back then, not many women had the opportunity to</p><p>traverse the whole of menopause and live to tell the tale. Besides, in ancient</p><p>Greece as well as in many other ancient civilizations, a woman’s value was</p><p>linked to her ability to bear children. Those who could no longer do so were</p><p>evidently not worthy of much interest or study.</p><p>Aside from some vague mentions, menopause remained basically</p><p>invisible to medicine until the nineteenth century. Right around the time</p><p>male physicians “discovered” women’s brains, they also stumbled upon</p><p>another disconcerting phenomenon: menopause. It might have been overall</p><p>progress in scientific inquiry, or perhaps that more women were living long</p><p>enough for menopause to not be ignored, but doctors eventually realized</p><p>menopause wasn’t some kind of freak accident. By then, there were indeed</p><p>colloquial expressions for menopause all over Europe, such as “women’s</p><p>hell,” “green old age,” and “death of sex.” The word menopause, though,</p><p>entered our vocabularies only in 1821, when French physician Charles de</p><p>Gardanne came up with the term, borrowing from Greek men (month) and</p><p>pauein (to cease or stop),</p><p>they</p><p>provide no guarantee of efficacy or safety. Since they’re not regulated, there</p><p>is also no double check to ascertain the supplement contains the indicated</p><p>amount of active ingredients listed. Because of this, selecting standardized</p><p>formulations is imperative. To make sure a formula is standardized, you’ll</p><p>want to check the percentage of active ingredients listed. For example,</p><p>when searching for a ginkgo biloba supplement, you want to be sure</p><p>extracts are standardized to contain a certain percentage (typically 25</p><p>percent) of ginkgo flavone glycosides, the herb’s active constituents.</p><p>Another way to ensure a dietary supplement is of high, uncontaminated</p><p>quality is to purchase products indicating testing by either the U.S.</p><p>Pharmacopeial (USP) Convention Dietary Supplement Verification</p><p>Program or ConsumerLab.com. Finally, while most supplements and herbal</p><p>remedies carry a low risk of side effects, some can interact with prescription</p><p>medications or come with contraindications, as noted below.</p><p>Botanicals</p><p>▷ BLACK COHOSH</p><p>Black cohosh (Actaea racemosa, Cimicifuga racemosa) belongs to the</p><p>North American buttercup family and is one of the most extensively</p><p>researched herbs for menopause. Native American women have used black</p><p>cohosh for centuries to relieve menstrual cramps and menopausal</p><p>symptoms. Clinical trials have examined this herb with about half reporting</p><p>decreases in hot flashes, which is not considered a consistent effect.</p><p>Nonetheless, this buttercup seems to specialize in soothing mild to</p><p>moderate night sweats and mood swings. In Germany, black cohosh is</p><p>approved for premenstrual discomfort and menopausal symptoms such as</p><p>hot flashes, heart palpitations, nervousness, irritability, disturbed sleep,</p><p>vertigo, and depression.</p><p>Although more research is needed, black cohosh doesn’t appear to have</p><p>estrogenic effects. As such, it may be helpful for cancer patients.</p><p>Usage: Hot flashes.</p><p>Scientific proof of efficacy: Medium.</p><p>Dosage: 40 mg per day of standardized extract. Due to the lack of long-</p><p>term safety studies, it should be used for a maximum of six months.</p><p>Precautions: Although black cohosh is generally well tolerated, it can</p><p>cause headaches. Rare cases of liver damage have been reported.</p><p>▷ CHASTE TREE BERRY</p><p>Contrary to what its name suggests, chaste tree berry (Vitex agnus-castus) is</p><p>often recommended to boost fertility and improve some symptoms of</p><p>menopause. However, while chaste tree berry seems to have hormone-</p><p>balancing effects, clinical trials have yet to show consistent relief of</p><p>menopause symptoms.</p><p>Usage: Menopausal complaints of various origin.</p><p>Scientific proof of efficacy: Low.</p><p>Dosage: 200–250 mg per day.</p><p>Precautions: Generally well tolerated. It may interact with some</p><p>medicines, such as birth control pills or drugs used to treat Parkinson’s</p><p>disease or psychosis.</p><p>▷ DONG QUAI</p><p>Dong quai (Angelica sinensis) has been used in traditional Chinese</p><p>medicine for over 1,200 years to treat menstrual pain and irregularity, as</p><p>well as hot flashes in menopause. Yet very little research has been</p><p>conducted to test its efficacy and clinical trials to date have not shown</p><p>effects on hot flashes. Caveat: Experts in Chinese medicine point out that</p><p>the preparations used in these trials are not the same as those used in their</p><p>practice.</p><p>Usage: Hot flashes.</p><p>Scientific proof of efficacy: Low.</p><p>Dosage: Up to 150 mg per day.</p><p>Precautions: Dong quai may interfere with blood-thinning medications,</p><p>such as warfarin, heparin, or aspirin.</p><p>▷ EVENING PRIMROSE</p><p>Evening primrose oil originates from the seeds of the flowering plant</p><p>Oenothera biennis. A rich source of omega-6 fatty acids, this oil is often</p><p>recommended for treating hot flashes, although clinical trials have shown it</p><p>to be no more effective than placebo. Nonetheless, combined with vitamin</p><p>E, it may help with breast tenderness.</p><p>Usage: Hot flashes.</p><p>Scientific proof of efficacy: Low.</p><p>Dosage: 2–6 g per day.</p><p>Precautions: Generally well tolerated. It may increase the effects of the</p><p>HIV medicine lopinavir.</p><p>▷ GINSENG AND MACA ROOT</p><p>The ginseng root is considered an adaptogenic herb, meaning it promotes</p><p>resistance to external and internal stressors, thereby supporting our physical</p><p>and mental health. In traditional medicine, Asian ginseng (Panax ginseng or</p><p>Panax quinquefolius) and maca root (Peruvian ginseng, Lepidium meyenii)</p><p>are said to heighten concentration, improve sexual function, and promote</p><p>arousal. A systematic review of randomized controlled trials indicates that</p><p>ginseng can improve symptoms of menopausal depression and low mood</p><p>while supporting libido and overall well-being. Despite its success in these</p><p>ways, ginseng doesn’t consistently help with vasomotor symptoms,</p><p>memory, or concentration.</p><p>Usage: Mood and libido.</p><p>Scientific proof of efficacy: Medium.</p><p>Dosage: 400 mg per day of standardized extract. Because of the lack of</p><p>long-term safety studies, its use should be limited to a maximum of six</p><p>months.</p><p>Precautions: Generally well tolerated. Insomnia is the most common side</p><p>effect, so it is best taken early in the day. Other potential side effects include</p><p>menstrual problems, breast pain, increased heart rate, high or low blood</p><p>pressure, headache, and digestive issues. Ginseng may interfere with blood-</p><p>thinning medications, such as warfarin, heparin, or aspirin.</p><p>▷ KAVA</p><p>Kava (Piper methysticum) is a pepper from the Pacific Islands. While kava</p><p>supplements possibly reduce anxiety to some extent, they have not been</p><p>shown to decrease hot flashes.</p><p>Usage: Hot flashes and anxiety.</p><p>Scientific proof of efficacy: Low.</p><p>Dosage: 50–250 mg per day.</p><p>Precautions: The FDA has issued a warning about kava because of its</p><p>potential to damage the liver. Kava can also cause digestive upset,</p><p>headache, and dizziness.</p><p>▷ PHYTOESTROGENS</p><p>Phytoestrogens are estrogen-like substances found in cereal, soy,</p><p>vegetables, and some herbs that act as weaker estrogens in the body. The</p><p>most common phytoestrogen supplements are isoflavones extracted from</p><p>soy and red clover, while flaxseeds are also often recommended. A review</p><p>of as many as twenty-one clinical trials indicates that phytoestrogens</p><p>decrease the number and frequency of hot flashes and improve vaginal</p><p>dryness. However, results differ depending on the type of phytoestrogen</p><p>used, as reviewed below.</p><p>SOY ISOFLAVONES</p><p>Some soy isoflavones (such as soy protein isolate, isoflavone-rich soy</p><p>extracts, or isoflavone capsules) can be effective in relieving mild-to-</p><p>moderate perimenopausal hot flashes. For example, a study of 60</p><p>postmenopausal women compared soy isoflavone supplements to HRT</p><p>for relief of hot flashes. After sixteen weeks, those taking isoflavones</p><p>experienced a 50 percent reduction in hot flashes, while those on HRT</p><p>had a 46 percent reduction. While more research is needed to confirm</p><p>these results, soy isoflavones may also have positive effects on bone</p><p>mineral density, reducing the risk of osteoporosis. However, they are not</p><p>effective against night sweats, insomnia, or depression. Something to</p><p>keep in mind is that soy effects vary according to genetic background,</p><p>and only 30 to 50 percent of Western women experience beneficial</p><p>effects. The main soy isoflavones are called genistein, daidzein, and S-</p><p>equol.</p><p>Usage: Hot flashes.</p><p>Scientific proof of efficacy: Medium.</p><p>Dosage: 40–80 mg per day. Because of the lack of long-term safety</p><p>studies, the use of isoflavones should be limited to a maximum of six</p><p>months.</p><p>Precautions: Generally well tolerated. The most common side effects</p><p>are gastrointestinal issues. Current evidence indicates that it’s safe for</p><p>women who have had or are at risk for cancer to eat soy foods, while it’s</p><p>still uncertain whether soy isoflavone supplements are safe for them.</p><p>Professional societies do not endorse soy isoflavone supplements for fear</p><p>of overconsumption.</p><p>RED CLOVER ISOFLAVONES</p><p>Red clover (Trifolium pratense) is one of the most widely researched</p><p>herbs for menopausal health. According to systematic reviews, red clover</p><p>isoflavones are not consistently effective for daytime hot</p><p>indicating the time at which a woman’s period</p><p>ends.</p><p>On brand for those times, the realization that menopause was something</p><p>worth addressing led clinicians to build a framework for it... as an actual</p><p>disease. A remarkable number of medical conditions, ranging from scurvy</p><p>to epilepsy and schizophrenia, were readily blamed on this baffling new</p><p>condition. This should come as no surprise considering the general mindset</p><p>was that some obscure connection between the uterus and the brain</p><p>rendered women susceptible to madness, or hysteria (from the Greek word</p><p>hystera, meaning uterus). For instance, what we now refer to as</p><p>premenstrual syndrome (PMS) was thought to be caused by the</p><p>“suffocation” of the womb filling with blood, or even the upward migration</p><p>of the womb within a woman’s body to suffocate her. Clearly, they argued,</p><p>this unhealthy link will also result in “climacteric insanity” after</p><p>menopause.</p><p>Consequently, drastic and often highly toxic practices emerged to deal</p><p>with the rebellious wandering womb. Hypnosis, vibrating devices, and</p><p>blasting the vagina with a jet of water are just a few well-documented</p><p>techniques. Opium, morphine, and lead-based vaginal injections are others.</p><p>Then physicians came up with an even more radical solution: surgery. They</p><p>argued that if the womb was diseased, it should be removed. In hindsight,</p><p>we now know that hysterectomies (the surgical removal of the uterus and</p><p>ovaries) plunge a woman into menopause almost overnight, potentially</p><p>worsening its symptoms altogether. So as surgery only exacerbated issues,</p><p>the asylum beckoned instead. Accounts abound of how women</p><p>experiencing symptoms of menopause were wrongly diagnosed as “crazy”</p><p>or “demented,” and as such, were locked up in mental institutions. The truth</p><p>is that these women likely suffered such tragic ends due to the misguided</p><p>treatments administered by their own doctors.</p><p>Fast-forward to the twentieth century. As women gained lifespan,</p><p>suffrage, and cultural power, menopause finally came to be understood as</p><p>worthy of medical attention, as opposed to institutionalization. One of the</p><p>most significant contributions to this shift in perspective came in 1934,</p><p>when scientists discovered the hormone estrogen. Notably, the term</p><p>estrogen itself was derived from the Greek oistros, which means frenzy or</p><p>mad desire—further reinforcing a historical trend to frame female</p><p>physiology through the lens of mental instability. Nonetheless, as science</p><p>moved forward, the link between loss of estrogen and menopause was also</p><p>found—which led only to updating the definition of menopause to be a</p><p>disease of “estrogen deficiency.” By extension, estrogen became a magical</p><p>elixir of youth in people’s imagination, and as such a profitable drug.</p><p>Pharmaceutical companies jumped at the opportunity, and estrogen</p><p>replacement therapy quickly became the treatment of choice for</p><p>menopause. As recently as 1966, Robert A. Wilson, MD, author of the</p><p>national bestseller Feminine Forever, declared the condition “a natural</p><p>plague,” calling menopausal women “crippled castrates.” But, Wilson</p><p>wrote, with estrogen replacement, a woman’s “breasts and genital organs</p><p>will not shrivel. She will be much more pleasant to live with and will not</p><p>become dull and unattractive.” Later, and perhaps unsurprisingly, evidence</p><p>emerged that the influential book had been backed by pharmaceutical</p><p>companies. Not all the propaganda was explicitly sponsored, though—it</p><p>just spread across culture like wildfire. David Reuben’s Everything You</p><p>Always Wanted to Know About Sex but Were Afraid to Ask (1969) had this</p><p>to say: “Once the ovaries stop, the very essence of being a woman stops.”</p><p>He added that “a postmenopausal woman comes as close as she can to</p><p>being a man,” correcting, “not really a man, but no longer a functional</p><p>woman.” Little by little, the idea that menopause was an estrogen</p><p>deficiency syndrome took hold, and it is still common in medical textbooks</p><p>and practices today.</p><p>On the other hand, the actual mechanisms by which estrogen impacts</p><p>mental health are a strikingly modern discovery. Only in the late 1990s did</p><p>scientists make a powerful breakthrough: our so-called sex hormones were</p><p>key not just for reproduction but for brain function as well. In other words,</p><p>the hormones inextricably involved with our fertility, with estrogen leading</p><p>the charge, turned out to be just as crucial in the overall functioning of our</p><p>minds. To give you a sense of how recent a finding this is, men had walked</p><p>on the moon thirty years prior. During those same thirty years on earth,</p><p>scores of women had been taking hormones in spite of the fact that nobody</p><p>had a clue about how estrogen really worked from the neck up.</p><p>MEDICINE AND BIKINI MEDICINE</p><p>Which brings us back to the twenty-first century. Today, menopause is</p><p>strictly ob-gyn territory, and the connections between our reproductive</p><p>system and our brain are no longer demonized but are mostly unaddressed.</p><p>At the same time, in a bizarre turn of events, most scientists now accept that</p><p>sex hormones are important for brain health, but also believe men’s and</p><p>women’s brains to be roughly the same, except for some functionalities</p><p>involved in reproduction.</p><p>Enter one of the major healthcare challenges of our times: bikini</p><p>medicine. Bikini medicine is the practice of reducing women’s health to</p><p>those body parts found beneath a bikini’s confines. It is saying that, from a</p><p>medical perspective, what makes a woman “a woman” is our reproductive</p><p>organs and nothing more. Aside from those organs, men and women have</p><p>been studied, diagnosed, and treated in the same exact way—as if we were</p><p>all men. This, as it turns out, is not only counter to reality but also</p><p>destructive in guiding medicine and science to protect women’s brains,</p><p>including those in menopause.</p><p>In the simplest terms, the vast majority of medical research has used the</p><p>male body as its exclusive prototype, “boobs and tubes” notwithstanding.</p><p>On top of that, as recently as the 1960s, the FDA made it standard practice</p><p>to deny women of childbearing potential access to experimental drugs and</p><p>clinical trials, claiming that doing so avoided any potential adverse effects</p><p>on the fetuses. The phrase woman of childbearing potential, however, was</p><p>taken to mean “any woman capable of becoming pregnant,” not solely those</p><p>who were. This meant that any woman from the age of puberty through</p><p>menopause, regardless of sexual activity, use of contraceptives, sexual</p><p>orientation, or even any desire to have a child in the first place, was</p><p>excluded from clinical trials. Where women’s brains had been dismissed for</p><p>centuries as flawed, they were now being rendered invisible for other</p><p>reasons entirely.</p><p>This woman-wide ban was enforced well into the nineties, which means</p><p>we have decades of medical research based on nearly male-only samples.</p><p>Shockingly, this is true right up to the present day, as countless drugs have</p><p>been put on the market that have never actually been tested on women. In</p><p>fact these drugs often haven’t been tested even on female animals. The vast</p><p>majority of preclinical studies still use only male animals, arguing that</p><p>variability in sex hormones may “confound empirical findings.” This</p><p>profoundly biased unisex system has been supplying the medical field with</p><p>data that either doesn’t apply or, at best, applies inconsistently to an entire</p><p>half of the world’s population.</p><p>Given that the male-dominated medical system has a long history of</p><p>vilifying menopause while sidelining the study of women’s brains, and that</p><p>research has been done mostly on men, and that men don’t go through</p><p>menopause, it’s really no surprise that the effects of menopause on brain</p><p>health have remained a mystery—a mystery “solved” with stigma and</p><p>stereotypes rather than with facts and information. To state the obvious, this</p><p>has had a catastrophic effect on medical research on the whole, and on the</p><p>field of women’s health in particular.</p><p>The consequences are especially clear when it comes to the health of our</p><p>brains. Because the truth is, women’s</p><p>brains are not the same as men’s</p><p>brains. They are hormonally, energetically, and chemically different. While</p><p>these differences have no deterministic effects on intelligence or behavior</p><p>and should never be used to reinforce gender stereotypes, they are crucial to</p><p>supporting brain health, especially after menopause. For some statistics</p><p>most people aren’t familiar with, women are:</p><p>Twice as likely as men to be diagnosed with an anxiety disorder or</p><p>depression.</p><p>Twice as likely to develop Alzheimer’s disease.</p><p>Three times more likely to develop an autoimmune disorder,</p><p>including those that attack the brain, such as multiple sclerosis.</p><p>Four times more likely to suffer from headaches and migraines.</p><p>More likely to develop brain tumors such as meningiomas.</p><p>More likely to be killed by a stroke.</p><p>Notably, the prevalence of these brain conditions changes from broadly</p><p>equal between men and women before menopause to a 2:1 or higher</p><p>female-to-male ratio after menopause. As for the impact of this change, a</p><p>woman in her fifties is twice as likely to develop anxiety, depression, or</p><p>even dementia in the course of her lifetime as she is to develop breast</p><p>cancer. Yet breast cancer is clearly recognized as a women’s health issue (as</p><p>it should be), while none of the brain conditions above are. And since</p><p>breast cancer fits within the “bikini medicine” framework, research and</p><p>resources have been appropriately devoted to curing it, while hardly any</p><p>effort has been directed toward menopause care for brain health.</p><p>Let’s be clear that menopause is not a disease and doesn’t cause any of</p><p>the mentioned illnesses. However, the underlying hormonal changes can put</p><p>a targeted strain on many organs, including the brain, especially when</p><p>ignored or left unattended. For most women, this can lead to various well-</p><p>known symptoms such as hot flashes and insomnia. For others, menopause</p><p>can potentially trigger severe depression, anxiety, or even migraines. For</p><p>others still, it might be a higher risk of developing dementia down the line.</p><p>So while the notions of hysteria and womb suffocation were made up, these</p><p>risks are real. They call for a clear, urgent response: comprehensive</p><p>research and effective strategies necessary to address the impact of</p><p>menopause on the brain. Not only do we need help minimizing those initial</p><p>symptoms, but it’s time to accelerate our understanding to prevent the</p><p>development of more severe issues in the future. Women’s medicine must</p><p>raise its sights—not only beyond the bikini but beyond reproduction as a</p><p>sole goal. It’s time to take an honest and rigorous look at what’s happening</p><p>in women’s bodies and brains as a whole, and to fully acknowledge the</p><p>systemic impact of menopause in the mix.</p><p>OUR BODIES, OUR BRAINS</p><p>Thus far, we have been looking at the effects of scientific knowledge (and</p><p>ignorance) at systemic and cultural altitudes. Historically, women have been</p><p>nothing short of tortured, both physically and psychologically, in the name</p><p>of menopause. We’ve been made to believe that menopause can render a</p><p>woman medically insane, while women of menopausal age and beyond</p><p>have been rendered invisible in society. This is dangerous, as culture has a</p><p>powerful effect on how we understand and experience menopause itself—</p><p>and Western culture has conditioned us to see the symptoms surrounding it</p><p>as the only meaningful aspects of this transition. While things have</p><p>certainly improved over time, this trauma has embedded itself into the</p><p>collective unconscious, influencing not only how a woman is perceived but</p><p>also how we at times perceive ourselves and our self-worth.</p><p>Many women have direct individual experiences with the effects of these</p><p>frameworks, and not just when going through menopause. Thanks to the</p><p>one-two punch of bogus beliefs and outdated conventions covered above,</p><p>our health concerns are routinely downplayed or dismissed. In cardiac care</p><p>and pain management, for example, it’s now a well-documented</p><p>phenomenon that female patients are much more likely than male patients</p><p>to be sent home and not treated at all, resulting in poorer outcomes. How</p><p>does this play out? When they are in pain, women are more likely than men</p><p>to be told their pain is psychosomatic, hypochondriacal, or stress-related.</p><p>This sounds like the nineteenth century, but it’s happening right now, all too</p><p>often culminating in a prescription for antidepressants or psychotherapy</p><p>rather than targeted care.</p><p>Given these tendencies, I’m sure you can imagine (or recall) the response</p><p>to any issues related to menopause being treated as fabricated or</p><p>unimportant. More broadly, healthcare professionals have often engaged in</p><p>a disheartening form of medical gaslighting, where they have historically</p><p>downplayed women’s health issues as a whole, and specifically neglected</p><p>women’s concerns around their mental health. As patients, we can therefore</p><p>grow accustomed to downplaying our own symptoms in turn, for fear of</p><p>appearing silly or oversensitive or even to avoid being patronized.</p><p>Unfortunately, brushing off a woman’s symptoms can lead to delays in</p><p>diagnosis and treatment, potentially costing us our quality of life and, if</p><p>we’re unlucky, worse.</p><p>As women, we’ve been taught to fear our hormones and doubt our brains.</p><p>Women’s brain health remains to this day one of the most under-researched,</p><p>underdiagnosed and undertreated fields of medicine. Not to mentioned</p><p>underfunded. Women in menopause in particular have been</p><p>underrepresented and underserved not only in medicine, but also in culture</p><p>and media. This is seriously overdue for a change—one that I hope science</p><p>will help bring forth, this time to support women instead of harming them.</p><p>In this chapter, we address the persistent issue of gender bias in</p><p>medicine, particularly the exclusion of women, and the inadequate</p><p>representation of various demographics within the existing research. The</p><p>glaring neglect of menopausal women in scientific studies is further</p><p>exacerbated by the insufficient inclusion of women of color, individuals</p><p>from diverse socioeconomic backgrounds, and those with differing gender</p><p>identities, among other important factors. This lack of representation is</p><p>detrimental to us all. Just as it is fundamentally flawed to consider women</p><p>and men as medically identical, it is erroneous to assume that all women</p><p>share the same access to well-informed doctors, fitness centers, or nutritious</p><p>food options. The disparities in access and resources can lead to negative</p><p>outcomes for brain health, which may in turn affect the experience of</p><p>menopause. Despite the significance of these considerations, there is a</p><p>surprising absence of research examining how these factors play out in real-</p><p>life situations. In an ideal world, accurate information and effortless access</p><p>to necessary resources and specialists would be available for optimal care</p><p>throughout our lives. However, given that our world is far from perfect, this</p><p>book aims to bridge some of these gaps and tackle potential challenges</p><p>specifically related to menopause. As a scientist, I strive to ensure that my</p><p>own research addresses these concerns and actively advocate that other</p><p>investigators adopt a similar approach and interest. By addressing these</p><p>disparities, we hope to foster a more inclusive and comprehensive</p><p>understanding of the neuroscience of menopause for all.</p><p>In this spirit, I’d like to remind everyone that the field of women’s health</p><p>advances as women’s rights evolve. Generations of women have fought for</p><p>us to have access to healthcare, to be included in clinical trials, to benefit</p><p>from higher education, and to be acknowledged as lauded contributors in</p><p>society. Nonetheless, we still strain under the yoke of income, power,</p><p>representation, and healthcare gaps. It’s time to take down the last taboos</p><p>regarding our bodies and our brains and, in doing so, create a culture of</p><p>understanding, acceptance, and support around menopause. While the work</p><p>of overcoming the stigma does not fall upon women alone, speaking out</p><p>loud in our collective voice has the power to yield</p><p>significant impact. This</p><p>is a legacy we could be proud to pass onto our daughters and</p><p>granddaughters, lightening the load for generations to come.</p><p>3</p><p>The Change Nobody Prepared You</p><p>For</p><p>WHAT IS MENOPAUSE?</p><p>After years of discussing menopause with patients, healthcare providers,</p><p>and the media, I realized there’s a great deal of confusion and</p><p>misinformation about menopause. Two things can help bring clarity and</p><p>reduce worry: (1) clarifying what menopause is and isn’t, and (2) separating</p><p>fact from fiction. Our ideas arrive to us and are transmitted through</p><p>language. So let’s start by looking at terminology, not necessarily as it is</p><p>commonly used in conversation but rather the way it is used in clinical</p><p>practice. The most important concepts are summarized in table 1 and</p><p>described below.</p><p>•••</p><p>Table 1. Glossary: What You Need to Know About Menopause</p><p>TERMINOLOGY</p><p>Premenopause, or reproductive stage</p><p>MEANING</p><p>The whole reproductive period before the menopause transition.</p><p>TERMINOLOGY</p><p>Menopause transition</p><p>MEANING</p><p>The period before menopause when the timing of the menstrual cycle</p><p>wobbles and the hormonal and clinical symptoms of menopause begin.</p><p>TERMINOLOGY</p><p>Menopause</p><p>MEANING</p><p>The ending of the menstrual cycle. Clinically speaking, the menopause</p><p>transition is complete after twelve consecutive months since the final</p><p>menstrual period. There are different ways menopause can occur: it can be</p><p>spontaneous or induced (see below). All women go through one or the</p><p>other.</p><p>TERMINOLOGY</p><p>Perimenopause</p><p>MEANING</p><p>A phase that starts toward the end of the menopausal transition and</p><p>continues into the first year after the final menstruation period. You’ve</p><p>exited perimenopause and begun menopause once you’ve had twelve</p><p>consecutive months without a period.</p><p>TERMINOLOGY</p><p>Postmenopause</p><p>MEANING</p><p>The stage starting twelve months after the final menstrual period.</p><p>TERMINOLOGY</p><p>Spontaneous, or “natural” menopause</p><p>MEANING</p><p>Menstruation stops when the ovaries run out of egg cells and the</p><p>production of estrogen and progesterone declines, as part of the aging</p><p>process. The vast majority of women worldwide will enter menopause aged</p><p>forty-nine to fifty-two years. Age can differ based on geographical location</p><p>and ethnic background.</p><p>TERMINOLOGY</p><p>Early or premature menopause</p><p>MEANING</p><p>Menopause occurring before age forty (premature) or forty-five (early). It</p><p>can occur as a result of:</p><p>Genetic factors</p><p>Polycystic ovary syndrome (PCOS)</p><p>Autoimmune disease</p><p>Infections</p><p>Surgery</p><p>Medical treatment</p><p>TERMINOLOGY</p><p>Induced menopause</p><p>MEANING</p><p>Menstruation ends due to the surgical removal of the ovaries</p><p>(oophorectomy) or the lapsing of ovarian function due to medical</p><p>procedures such as chemotherapy or radiation.</p><p>TERMINOLOGY</p><p>Surgical menopause</p><p>MEANING</p><p>Menopause provoked by surgical procedures. It can occur at any age as a</p><p>result of:</p><p>Bilateral oophorectomy: both ovaries are removed.</p><p>Bilateral salpingo-oophorectomy (BSO): both ovaries and fallopian tubes</p><p>are removed.</p><p>Total hysterectomy: the uterus, cervix, ovaries, and fallopian tubes are</p><p>removed.</p><p>Note that a partial hysterectomy (removal of the uterus but not the</p><p>ovaries), ovarian cyst removal, or endometrial ablation does not cause</p><p>menopause but can affect blood flow to the ovaries, prompting</p><p>menopausal symptoms at an earlier age.</p><p>TERMINOLOGY</p><p>Medical menopause</p><p>MEANING</p><p>Menopause provoked by medical treatments that cause temporary or</p><p>permanent damage to the ovaries. It can occur at any age, often as a</p><p>result of:</p><p>Radiation or chemotherapy</p><p>Estrogen blockers (tamoxifen): medications that block estrogen’s action in</p><p>specific tissues</p><p>Aromatase inhibitors: medications that stop estrogen production</p><p>throughout the body</p><p>GnRH agonists: medications that keep the ovaries from making estrogen</p><p>and progesterone, thus stopping ovulation</p><p>In medical terms, menopause is the one-year anniversary of your final</p><p>menstrual period (FMP). Long story short, it is confirmed only once you</p><p>have missed your period for a year or more, which means a yearlong</p><p>waiting game is required before you can deem your final period genuinely</p><p>final. Then, and only then, are you officially postmenopausal.</p><p>While this makes sense from a clinical perspective, this framework can</p><p>be quite confusing in real life, and for good reason. This description of</p><p>menopause implies that one will experience a singular moment that starts</p><p>on a specific day, much like menstruation did some decades prior. You’d</p><p>think that one day you suddenly stop having your period, and that’s that.</p><p>Many women who have gone through menopause might utter a wry chuckle</p><p>at this, knowing better. In actuality, menopause is not a day that arrives but</p><p>a dynamic and sometimes lengthy process that can span many years. It is</p><p>also a time during which whatever your previous sense of normalcy has</p><p>been, it’s now in a state of flux and change.</p><p>How Menopause Unfolds: Ages and Stages</p><p>The complexity of the menopause transition is just starting to be formalized</p><p>in medical textbooks, some of which now describe menopause as coming in</p><p>several phases. In more succinct terms, we are looking at three main stages:</p><p>premenopause, perimenopause, and postmenopause.</p><p>Figure 2. The Three Stages of Menopause</p><p>As shown in figure 2:</p><p>▷ PREMENOPAUSE</p><p>As long as you have a regular cycle, you are in the “reproductive” or</p><p>premenopausal stage. It starts with puberty and ends as the menopause</p><p>transition begins.</p><p>▷ PERIMENOPAUSE</p><p>Once your period starts becoming irregular, you’re entering the menopause</p><p>transition, which is often called perimenopause. At first, your period might</p><p>go a little wonky. It might show up early or late, be longer or shorter, get</p><p>more or less painful, or be heavier or lighter. In other words, it won’t be</p><p>consistent—everything is up for grabs. And then at some point it won’t</p><p>show up at all for two months or more. At this time, symptoms like hot</p><p>flashes, as well as possible shifts in sleep quality, mood, and cognition are</p><p>more likely to flare up, and even the bravest among us may feel they’ve</p><p>stayed too long at the fair. The average age that perimenopause starts is</p><p>forty-seven years, but it varies depending on ethnicity, genetics, and</p><p>lifestyle factors. The transition usually lasts four to eight years, but can be</p><p>as long as fourteen years.</p><p>▷ POSTMENOPAUSE</p><p>A full year after your final menstrual period, you are considered</p><p>postmenopausal. However, let’s say you don’t have a period for a year, and</p><p>then, boom, you suddenly have a surprise one—the clock resets, and you</p><p>are once again in perimenopause! Back at square one, you will again work</p><p>toward the postmenopausal stage. Importantly, symptoms typically start to</p><p>recede or disappear a few years after the final menstrual period, though this</p><p>is not always the case. Most women experience menopause between age</p><p>forty and fifty-eight, and the average age at menopause is fifty-one to fifty-</p><p>two. However, the exact timing varies widely from person to person.</p><p>Additionally, this map applies only to women undergoing spontaneous</p><p>menopause, which occurs when menstruation stops in midlife as a result of</p><p>the endocrine aging process. Many women experience menopause at</p><p>younger ages and for different reasons.</p><p>▷ EARLY OR PREMATURE MENOPAUSE</p><p>Some women develop menopause before age forty-five (early menopause)</p><p>or even before age forty (premature menopause). About 1 to 3 percent of</p><p>women who experience early or premature menopause do so due to the</p><p>ovaries producing low levels of reproductive hormones, a condition known</p><p>as primary ovarian insufficiency (POI). Other women experience</p><p>menopause prematurely or early because of autoimmune or metabolic</p><p>disease, infection, or a genetic cause. However, the most common causes of</p><p>premature or early menopause are surgery and some medical treatments. In</p><p>this case, menopause is called induced, and differs from spontaneous</p><p>menopause in many ways.</p><p>▷ INDUCED MENOPAUSE</p><p>Many women undergo induced menopause, which is when ovulation ends</p><p>due to either the surgical removal of the ovaries (oophorectomy)</p><p>or the</p><p>lapsing of ovarian function due to medical procedures such as</p><p>chemotherapy or radiation. Women who have their ovaries surgically</p><p>removed while still having a menstrual cycle will find themselves in</p><p>menopause soon after the intervention. Women whose ovaries stop working</p><p>for other medical reasons can also develop menopause earlier in life. This is</p><p>referred to as medical menopause. Surgical menopause may come on very</p><p>quickly, whereas medical menopause can happen over a time frame of</p><p>weeks or months. It’s important to note that a partial, or simple,</p><p>hysterectomy, where the uterus is removed but the ovaries are left in place,</p><p>will stop menstruation but not ovulation. As such, it will not prompt early</p><p>menopause. However, hormonal production may decrease, and blood flow</p><p>to the ovaries may be reduced, too. This may prompt the symptoms of</p><p>menopause earlier than expected.</p><p>How Does Menopause Happen?</p><p>To fully appreciate what our bodies experience during menopause, we first</p><p>need to clarify how hormones function before menopause. During our</p><p>reproductive years, an intricate dance of hormonal feedback loops occurs</p><p>approximately every 28 days. The main sex hormones involved are estrogen</p><p>(the technical term is estradiol), progesterone, follicle-stimulating hormone</p><p>(FSH), and luteinizing hormone (LH). As you can see in figure 3, they rise</p><p>and drop at varied points during the menstrual cycle, spanning from the first</p><p>day of your period through the day before your next period.</p><p>The first half of the menstrual cycle is called the follicular phase. At this</p><p>time, the hormones FSH and LH rise to stimulate the growth of several</p><p>follicles, each containing an egg cell from the ovaries. As the follicles grow,</p><p>estrogen prompts the growth of the uterine lining to provide the egg with</p><p>the support it needs to host a baby. Once estrogen levels are sufficiently</p><p>high, a surge in LH causes the so-called dominant follicle to burst and</p><p>release the mature egg into the fallopian tube. This process is known as</p><p>ovulation, which occurs mid-cycle. That’s when pregnancy is most likely to</p><p>occur.</p><p>Figure 3. Sex Hormones During the Menstrual Cycle</p><p>The second half of the cycle is called the luteinizing phase. If pregnancy</p><p>has occurred, estrogen and progesterone remain high to prevent the womb’s</p><p>lining from being shed so the placenta can develop. If pregnancy has not</p><p>occurred, these hormone levels drop instead, prompting the uterus to shed</p><p>its lining, cuing menstruation.</p><p>Although the menstrual cycle is relatively complex, all generally goes to</p><p>plan as long as these hormones are on the same page, supporting and</p><p>regulating one another in harmony. That is, until a major event occurs to</p><p>disrupt this fine-tuned balance: the arrival of menopause. When a woman is</p><p>transitioning toward menopause, her ovaries run out of eggs and start</p><p>producing less estrogen. However, this isn’t a linear or steady process, as</p><p>estrogen doesn’t give up so easily.</p><p>As you can see in figure 4, estrogen’s concentration doesn’t drop all at</p><p>once but can fluctuate wildly as it declines. While not all women exhibit</p><p>these changes, the “before menopause” part of the graph looks broadly flat.</p><p>That’s because estrogen concentration remains consistent thanks to its</p><p>levels rising and falling at a regular rhythm with the menstrual cycle. The</p><p>“after menopause” graph is also virtually flat, as estrogen levels are steadily</p><p>low at this stage. But the “during” graph looks like the output of a</p><p>seismograph during an earthquake. As the length and frequency of the</p><p>menstrual cycle become increasingly irregular during the menopause</p><p>transition, estrogen’s dramatic peaks and valleys make its concentration</p><p>fluctuate just as widely. Estrogen is not the only hormone that’s having ups</p><p>and downs. As the feedback loops that were so carefully regulating all sex</p><p>hormones go out of synch, progesterone eventually bottoms out, while FSH</p><p>and LH increase instead. This hormonal roller coaster can create or</p><p>contribute to the seemingly random and often unpredictable physical and</p><p>psychological repercussions many women experience during menopause.</p><p>Figure 4. Estrogen Concentration Before, During, and After the Menopause Transition</p><p>So now we’re looking at two ways that the clinical framework for</p><p>menopause can make the whole process confusing. First off, menopause</p><p>doesn’t happen overnight. Second, while all women experience menopause,</p><p>every woman’s experience is different. Each of us has a unique hormonal</p><p>fingerprint, a unique reproductive system, and a unique brain. While this</p><p>individuality has yet to be formalized in medicine, it’s clear that both the</p><p>timeline and the symptoms of menopause can vary greatly from person to</p><p>person. All of this has led not only to lack of clarity among patients, but</p><p>also to some widespread inaccuracies around menopause itself, which we’ll</p><p>now proceed to debunk.</p><p>MENOPAUSE FAQS</p><p>Is menopause an illness or a disease?</p><p>Menopause is a physiological stage of life. While the symptoms</p><p>may not feel normal and the actual challenges surrounding it can</p><p>feel anything but ordinary, menopause is not an illness, a disease, or</p><p>a pathological condition. It is a transition. It doesn’t need curing or</p><p>fixing. It does need addressing and managing, if necessary.</p><p>Does menopause happen when you’re old?</p><p>Most women develop menopause in their forties and fifties. On</p><p>average, menopause occurs around age fifty-one to fifty-two, which</p><p>is not old by any standards. Besides, recent studies indicate that the</p><p>actual average age of menopause across the globe is forty-nine, so</p><p>even earlier. As mentioned already, the exact timing also varies</p><p>widely from person to person, spanning from the late thirties to the</p><p>early sixties.</p><p>Are blood tests necessary to diagnose menopause?</p><p>Since periods become less frequent during the menopause</p><p>transition and one gets more used to missing them, it may be hard to</p><p>know when they’ve stopped for good, leaving many women</p><p>wondering if they’re in menopause or not. I am often asked if</p><p>there’s a simple hormone test that can tell if you’re nearing</p><p>menopause or are already past it. The answer is no. Blood tests can</p><p>be helpful but are not necessary to diagnose menopause. If you</p><p>suspect that you’re in perimenopause or want to know if you’re past</p><p>menopause, the best thing to do is to have a complete medical</p><p>examination by a qualified healthcare professional. The diagnosis is</p><p>based on age, medical history, symptoms, and period frequency.</p><p>Blood work can be used as supportive information, but more often</p><p>than not, it isn’t needed.</p><p>Generally speaking, hormone tests are unnecessary to tell if a</p><p>forty-seven-year-old woman with irregular periods is in</p><p>perimenopause (most likely she is), or if a fifty-eight-year-old</p><p>woman with no period for years is postmenopausal (most likely she</p><p>is). Testing is instead recommended to evaluate fertility problems or</p><p>when periods stop at an early age, as with POI. Another reason to</p><p>test is for polycystic ovary syndrome (PCOS), a hormonal condition</p><p>that can impact menstrual regularity and fertility. Labs may also</p><p>help determine menopausal status for women who no longer have a</p><p>period due to medical interventions. These include a partial</p><p>hysterectomy (the surgical removal of the uterus but not the ovaries)</p><p>or an endometrial ablation (a procedure that removes the lining of</p><p>the uterus). These procedures stop your menstrual period but don’t</p><p>stop ovulation. In this case, the occurrence of menopausal</p><p>symptoms is the first indication of menopause, with blood work</p><p>providing supporting evidence. In such cases, the levels of estrogen</p><p>and other hormones, chiefly FSH and another hormone called</p><p>inhibin B, are measured. Inhibin B regulates FSH production, and it</p><p>can serve as a marker for ovarian function and follicular content.</p><p>Normative values are in table 2. When estrogen and inhibin B are</p><p>low, FSH is high, and a woman has not had a menstrual period for a</p><p>year, it is generally accepted that she has reached menopause.</p><p>However, a single lab test can be tricky because these</p>
- Relato de Experiênci1
- Prevenção de ISTs e AIDS
- Cartilha IST: Prevenção e Sexualidade
- Comportamento_Agressivo_no_TEA_CP_107
- Plano de Ensino Mamografia
- beneficios-leite-materno-mae
- Cancer de Mama
- Metodos não farmacologicos de alivio da dor
- Exame Papanicolaou: Coleta e Prevenção
- A IMPORTÂNCIA DA ANTROPOLOGIA E SUAS INTERFACES NA SOCIEDADE MODERNA
- Problema 06- módulo 10
- Problema 09-módulo 10
- anamnese vasectomia
- GINECO-OBSTETRICA INATIVO - 2022 Código da questão: 172321 O assoalho pélvico é um conjunto de partes moles que fecham a pelve, sendo formado por m...
- Questão 4 A lâmina produzida com amostra coletada no teste de Papanicolaou, de uma paciente com diagnóstico colpocitológico negativo para lesões de...
- São funções do enfermeiro assistencial, exceto: a) Diagnosticar as necessidades de enfermagem, elaborar e executar planos de Sistematização da Assi...
- Questão 4 I FISIOPATOLOGIA CLINICA EM UROLOGIA E Código da questão: 103099 GINECO-OBSTETRICA INATIVO - 2022 0 períneo fica localizado na parte infe...
- mulheres brasileira rastreio do cancer do colo do utero qual o intervalo
- Pacientes que apresentam hiperatividade da musculatura do assoalho pélvico podem apresentar como sintomas: a. Distopias. b. Fraqueza da musculatu...
- A incontinência urinária de urgência é caracterizada por: a. Perda de urina quando tosse. b. Sensação de não esvaziamento da bexiga. c. Noctúria...
- Qual o benefício do decúbito lateral esquerdo durante o parto? a. Promove maior oxigenação fetal. b. Aumenta o plano de saída da pelve. c. Posiç...
- A eclâmpsia nas grávidas é caracterizada por: Escolha uma opção: a. Hipertensão arterial. b. Afastamento dos músculos retoabdominais. c. Diabete...
- A eclâmpsia nas grávidas é caracterizada por: a. Convulsões. b. Proteinúria e aumento de peso. c. Hipertensão arterial. d. Afastamento dos músc...
- 0- De acordo com o Manual de Controle dos Cânceres do Colo do Útero e da Mama (2013), qual é a recomendação de conduta no resultado do exame mamogr...
- Sobre a infecção por Treponema pallidum, o agente etiológico da sífilis, é correto afirmar que: Não causa nenhuma doença congênita. Causa abort...
- deveres do psicologo em relação á possibilidade de quebra de sigilo profissional, relacionado a violencia de genero
- Iniciativas de promoção da saúde mental
- Políticas de gestão de resíduos sólidos
Perguntas dessa disciplina
Grátis
Grátis