When estrogen declines for any reason, including the gradual slowing of estrogen production that occurs with aging, a woman is at risk of developing a broad array of health issues. Understanding how estrogen keeps you healthy and vital is one of the first steps to owning your health. Let’s take a look at what happens as estrogen begins to decline or becomes deficient and why considering bioidentical hormonal therapy can address and ameliorate symptoms, reverse certain conditions, and even protect against the development of certain diseases.
For all the years your body produces estrogen in relative abundance, your cardiovascular system benefits from significant protection against the precursors to heart disease, including hypertension, high blood pressure, and blood sugar imbalance. As estrogen declines, your risk for cardiovascular disease begins to climb. Heart disease claims the lives of more than 290,000 women in the United States each year. By the time you enter menopause, the estrogen buffer begins to disappear. Eventually, women’s risks for heart attack and other forms of cardiovascular disease become roughly the same as those for men.
The loss of estrogen results in
Taking bioidentical estrogen, along with progesterone, can protect you from developing cardiovascular disease by controlling blood pressure, preventing plaque from forming in arteries, managing levels of unhealthy cholesterol, and preventing the thickening of the heart wall. Estradiol, or E2, has particular importance to cardiovascular function and health. An abundant body of research has demonstrated that E2
Maintaining healthy levels of estrogen can contribute significantly to your cardiovascular function, as well as offer you protection against heart attack and stroke.
Estrogen’s Role in Metabolism and Weight Management
One of the major reasons for weight gain in women throughout their forties and fifties (and even earlier) is dwindling estrogen levels. Too little estrogen can make you struggle to lose weight, even when you are making all the right choices in your diet and exercise. This weight struggle can be mentally and emotionally debilitating, as well as physically unhealthful. Indeed, many women think that estrogen replacement can cause weight gain—again, this is another misconception about HRT!
Inflammation is a source of aging, a catalyst for disease, and a trigger for pain and discomfort throughout the body. That’s not to say that inflammation is inherently bad or dangerous. The inflammatory response evolved for good reason. Inflammation serves an important function, mobilizing the immune system to respond to injury and the presence of foreign, potentially harmful substances. It’s when inflammation becomes chronic and excessive that it causes problems, which can affect and undermine nearly every physiological system, organ, tissue, and cell in the body. From cancer and cardiovascular disease to osteoporosis and obesity, excess inflammation is a cause of and contributor to disease and dysfunction.
With people living longer than ever before, the long-term dangers of inflammation have become increasingly relevant to our health. Inflammation is the result of a mobilization of the immune system to neutralize a threat to the body, whether in the form of a virus or other pathogen, a chemical toxin or other environmental irritant, or an injury or trauma. Sometimes inflammation is perceptible—we can feel its effects in our stiff muscles and joints, our aching knees. Common symptoms of inflammation include the following:
But inflammation often exists in the body without symptoms and without our awareness. This silent presence of inflammation is no less dangerous—in fact, it is more so. What causes inflammation? A lack of estrogen and other hormones is one significant factor, but there are other triggers of inflammation, including
It is impossible for any of us to shield ourselves completely from these inflammatory triggers, but you can do a lot to reduce excessive, chronic, and unhealthy inflammation by eating well, getting high-quality sleep, managing stress, and taking steps to minimize your exposure to chemical toxins. Bioidentical estrogen and other hormones can also help you limit inflammation and oxidative stress. Estrogen works as a powerful anti-inflammatory agent, increasing production of biochemicals that limit and reduce inflammation. One of estrogen’s important tasks in a woman’s body is its function as an antioxidant, limiting the proliferation of free radicals, which, along with making the body more vulnerable to cancer, further add to oxidative stress, exacerbating aging.
Free radicals create by-products, or oxidative stress, which, like inflammation, corrode the body and cause aging and disease. When a woman loses estrogen over the course of perimenopause and menopause, she loses a great deal of this protective antioxidant power. Without sufficient estrogen, women are more likely to experience excessive, aging, damaging inflammation—as well as the pain that often accompanies it. The pain and stiffness that many women experience during perimenopause and menopause is related to their declining hormones, including declines in estrogen.
Estrogen plays a significant role in the health, vitality, and function of your immune system, priming it to ward off infection and disease. As estrogen fluctuates and declines—whether during your monthly cycle, during and after pregnancy, or as part of perimenopause and menopause—your immune system can become vulnerable. Specifically, estrogen deficiency reduces levels of B cells and T cells, the workhorse cells of the immune system. Estrogen deficiency also increases levels of pro-inflammatory cytokines, which interfere with healthy immune function.
Women are disproportionately affected by autoimmune diseases. To date, researchers have identified more than 80 autoimmune diseases, and more than three-quarters of these diseases, such as multiple sclerosis, rheumatoid arthritis, Crohn’s disease, and thyroid disorders, occur more often in women than in men. Over the past few decades, there has been a dramatic rise in autoimmune diseases—a disturbing trend that scientists cannot fully explain, and one that will continue to affect women in far greater numbers than men.
Besides declining estrogen and hormonal levels, other risk factors for disrupted immune function and autoimmune disease include genetics, lifestyle, and behavior (including stress, sleep, diet, and exercise, all of which are themselves affected by estrogen). Exposure to environmental toxins is also a likely culprit in the development of autoimmune disease. A woman’s risk for autoimmune disease also increases as she ages, as does the risk of cancer, cardiovascular disease, and other diseases, in part because women are living longer than in previous generations.
All autoimmune diseases have one unifying characteristic: they are the result of the immune system turning on the body, attacking healthy cells rather than foreign invaders that pose a threat. While autoimmune diseases display a range of symptoms, several symptoms are common to many of them:
Estrogen protects your immune system. Women with chronically low estrogen and women who enter perimenopause or menopause earlier in life are at greater risk for developing some autoimmune diseases than are women who begin menopause later in life. If you already suffer from one or more immune disorders, continued low estrogen might worsen your situation. Multiple sclerosis, rheumatoid arthritis, and Sjögren’s syndrome (which causes dry eyes and dry mouth) are some common autoimmune diseases exacerbated during menopause because of deficient estrogen.
Pregnancy, on the other hand, with its flood of estrogen, progesterone, and other hormones, frequently has a beneficial effect on autoimmune disease. Many women with autoimmune diseases such as multiple sclerosis and rheumatoid arthritis experience an alleviation or cessation of symptoms while they are pregnant and see a return or increase of symptoms after giving birth, which corresponds to falling levels of estrogen.
Estrogen stimulates the production of anti-inflammatory, immune-boosting cytokines, which in turn protect against and help alleviate and slow progression of certain autoimmune diseases. My patients who have multiple sclerosis, rheumatoid arthritis, Sjögren’s syndrome, and other autoimmune diseases respond to estrogen treatment. If you are dealing with any one of these conditions, discuss with your physician how you can be helped with an HRT plan.
Vivienne became my patient when she had turned sixty-five. A professor of art history at a nearby university, Vivienne had short white hair and piercing blue eyes. She had lived an interesting life—lecturing in Europe, the Middle East, and the United States on her specialty, Islamic art—and was well known for being a mesmerizing teacher.
Vivienne sought me out because she’d heard that I might be able to address her “slipping memory,” as she described it. I would treat Vivienne for the last twenty years of her life. However, what we didn’t know when Vivienne first came to see me was that she’d been in early menopause since she was in her late forties, when she began to have memory lapses, which now were worsening. Although she was able to stem the tide of total cognitive decline for the twenty years she was my patient, we were not able to eradicate all the damage already done. I can say with confidence that, had I met Vivienne when she first noticed her symptoms, she would have lived to see ninety with all her mental faculties intact.
Estrogen is essential to the overall health and function of your brain. Estrogen fuels and regulates brain activity, and it helps maintain the brain’s structural health and integrity. Estrogen participates directly in supporting cognitive functions, protecting and enhancing learning and memory, alertness and focus, decision-making and planning. Estrogen is a major player in the dynamic biochemical balance of hormones, neurotransmitters, and other neurochemicals that affect every aspect of how a woman thinks, feels, and functions. Estrogen receptors throughout the brain’s complex networks work with those neurotransmitters and other neurochemicals to process and stabilize memory, learning, and emotion.
Changes to estrogen levels affect mental clarity, the sharpness and responsiveness of mental function, and memory—often particularly verbal memory and spatial memory. Brief, temporary cognitive and mental deficits can be associated with low estrogen points in the monthly cycle. Feelings of mental fogginess or sluggishness, difficulty with word retrieval, and other symptoms of cognitive fatigue may occur when estrogen levels fall during the month. The overall gradual decline of estrogen during perimenopause and menopause often brings significant and lasting changes to the cognitive function and memory of women in middle age and beyond. Diminishing estrogen also increases the risk of developing neurodegenerative disease.
Estrogen exerts powerful effects over memory, learning processes, and other cognitive functions. Estrogen elevates production of several neurotransmitters (serotonin, norepinephrine, and dopamine, the chemical messengers that communicate between cells in the brain). These neurotransmitters influence memory and emotional processing. Estrogen supports brain plasticity and the formation of dendrites, tiny neural fibers that facilitate the brain’s ability to process information.
Verbal facility and memory may change noticeably during menopause, when estrogen declines. Many women experience this symptom of menopause, the fumbling to remember a commonplace word, forgetting a person’s name or the name of a street you drive along routinely. Almost every day, a new patient arrives telling me of her frustration at her cognitive decline.
Estrogen provides a crucial protection against deterioration of brain cells and loss of cognitive skills and memory. Estrogen increases BDNF, brain-derived neurotrophic factor, a neurochemical that helps brain cells survive longer and is essential to overall brain health. Estrogen also provides specific, powerful protection against the development of neurodegenerative disease, including Alzheimer’s disease and Parkinson’s disease, two of the most common neurodegenerative diseases for women. Indeed, women are twice as likely as men to develop Alzheimer’s disease.
There is much we do not yet know about the catalysts for and development of neurodegenerative disease or about the factors that protect against it or make it worse. That said, there is tremendous evidence indicating that, for women, estrogen plays a significant role in protecting against or delaying neurodegeneration and the development of Alzheimer’s and Parkinson’s. Estrogen promotes healthy neural growth and repair and encourages and supports the growth of new brain cells. Estrogen also supports healthy blood flow to the brain and reduces beta-amyloid, a neurotoxic protein linked to Alzheimer’s disease. Estrogen’s stimulation of dopamine production and support for dopamine’s effectiveness may guard against Parkinson’s.
The anti-inflammatory powers of estrogen may be another form of protection against these neurodegenerative diseases—and the loss of this protection against inflammation when estrogen diminishes may be one way that estrogen influences women’s risk of developing neurodegenerative disease. Women who use estrogen replacement therapy have significantly lower incidence of Alzheimer’s disease.
Estrogen can not only prevent and slow the progression of neurodegenerative diseases but can also be used to treat them. The timing of estrogen therapy appears to make a significant difference in its ability to protect the brain and cognitive functions. Research suggests that estrogen therapy used during midlife, near the time of the initial, dramatic declines in estrogen during perimenopause and the beginning of menopause, has the greatest impact on long-term cognitive health. Estrogen therapy used later in life, after prolonged estrogen deficiency, may not be as effective in protecting and restoring cognitive function. In other words, memory loss that comes with estrogen deficiency may not be entirely recoverable, even after estrogen therapy is started.
Research also indicates that it isn’t your age but the length of estrogen deficiency that affects the ability of supplemental estrogen to protect the hippocampus, a brain area critical to learning, memory, and emotion. (The earliest degeneration associated with Alzheimer’s disease begins in the hippocampus.) The timing of estrogen therapy may also play a role in a woman’s risk for Alzheimer’s disease. While many studies show the protective effects of estrogen in reducing risk for Alzheimer’s, there is also evidence that estrogen therapy has its most powerful protective effects against Alzheimer’s when it is used early, at the beginning of menopause. Evidence also suggests that intermittent dosing of chemicalized estrogen may interfere with healthy cognition.
Bioidentical estrogen and other bioidentical hormones fortify and improve cognition, memory, and the structural health of the brain, without many of the risks posed by chemicalized hormone substitutes. As previously stated, they also can serve a critical purpose in slowing or preventing neurodegenerative diseases like Alzheimer’s and Parkinson’s.
Estrogen plays a significant role in regulating mood, preventing mood swings, and triggering or exacerbating depression and anxiety. When estrogen is low, you are likely to feel unmoored emotionally. You may feel you can no longer control, manage, or predict your emotions from one day, or even one hour, to the next. During the years before and throughout perimenopause and in early menopause, many of my patients complain of severe and erratic mood swings. They also experience an increase in a general, almost constant anxiety. Some women experience a creeping kind of depression that seeps into and sometimes dominates their lives. Not all women experience these, but anxiety, depression, and other mood problems become increasingly common with age—and the decline of estrogen contributes to that escalating risk.
Estrogen is critical to regulating mood. Specifically, estradiol (E2) is the estrogen compound that contributes most directly and effectively to regulating and balancing mood. The dips in mood that many women experience at points during their monthly cycles—days of feeling low, depleted, sometimes overcome with sadness—are largely due to natural drops in estrogen. One of estrogen’s important functions is as a monoamine oxidase (MAO) inhibitor. MAO is an enzyme that inactivates serotonin. By capping levels of MAO, estrogen enables serotonin and other mood-regulating neurotransmitters to remain active at healthy levels. Estrogen also works to control anxiety and panic attacks.
Estrogen is a powerful natural bulwark against depression. Insufficient estrogen can trigger depression even in women who might not otherwise be vulnerable to this debilitating emotional disorder. As mentioned, depression is more common for women in perimenopause and menopause, in large part because there is a diminishing supply of estrogen to balance and regulate mood. Fluctuating estrogen levels also affect mood and depression that are connected to pregnancy and childbirth. The plummeting of estrogen that occurs in the immediate aftermath of giving birth is one key factor that contributes to postpartum depression and, less frequently, to postpartum psychosis.
Major depression disorder (MDD) affects tens of millions of adults in the United States, causing hidden pain—and women suffer in greater numbers than men do. According to the National Institutes of Health, MDD afflicts slightly more than 8 percent of women in a given year, compared with 5 percent of men. Millions more women struggle with chronic or recurrent depressive symptoms that degrade their quality of life, interfere with their relationships, undercut their professional abilities, and diminish their energy and joy.
Bioidentical estrogen and other hormones are highly effective at alleviating depression in women—in my experience, far more so than conventional antidepressant pharmaceuticals. This is not to dismiss or discount the efficacy of these medications and their importance for many women who struggle with depression. However, while recognizing that SSRIs and other antidepressant drugs are necessary and sometimes lifesaving medications for women, I also believe they are overprescribed and overused, and their side effects not well understood. (See chapter 6 for more information on the impact of medications, including antibiotics.)
If you suffer from depression, taking bioidentical estrogen may provide significant protection and relief without some of the risks associated with conventional pharmaceutical depression treatment. While estrogen therapy for depression and other mood disorders won’t be right for every woman, I believe it can be effective for many who are currently not being treated at all or who are being treated with medicines.
A word of caution: never go off medication or switch medications on your own without the close guidance and support of your physician.
Estrogen exerts significant influence over anxiety levels. Estrogen-related anxiety occurs as part of the monthly cycle, as well as during perimenopause and menopause. Postpartum anxiety is also related to the steep drop in estrogen after birth. Estrogen helps increase calming neurotransmitters, including serotonin and GABA, while regulating levels of norepinephrine and adrenaline, which have an excitatory effect. In this way, you can think of estrogen as having a balancing effect on your mood.
In the extreme, low estrogen can lead to panic attacks—a frightening form of anxiety that can lead to a disorder requiring a physician’s care. The hallmark symptoms of panic attacks include a racing and/or irregular heartbeat, shortness of breath, chest pain, and intense feelings and sensations of fear and even terror. Although not common, some women in perimenopause experience panic attacks for the first time in their lives—though often these do not lead to a full-blown disorder. (Again, by understanding your body and how it changes over time and even within a particular month, you can cue in to these symptoms of anxiety and take steps to curtail the reactions so they don’t develop into a more serious disorder.)
Specifically, estrogen helps regulate and stimulate production of several neurotransmitters that have positive, stabilizing effects on mood. Estrogen also stimulates production of serotonin, norepinephrine, dopamine, and GABA, important mood-regulating neurotransmitters.
Sleep’s Effects on Mood, Depression, Anxiety, and Stress
If you are in perimenopause or in menopause, then you, like many of my patients, are probably experiencing difficulty sleeping; indeed, it’s a hallmark of estrogen deficiency. Estrogen-related sleep problems are also common for women at points in their monthly cycle when estrogen is low. Regardless of her age or stage in life, when a woman has naturally low levels of estrogen or uses the low-dose chemicalized estrogen found in oral contraceptives, she is more likely to experience sleep difficulties.
Even women who have slept soundly and well for most of their lives can find themselves struggling to fall asleep and stay asleep as their estrogen levels fluctuate throughout perimenopause and menopause. Other symptoms of menopause, particularly night sweats, can intrude on sleep and be disruptive to sound nightly rest.
Sleep problems and mood problems go hand in hand. Sleep and mood exist in a bidirectional relationship—each exerts a significant influence over the other. They are both a symptom of depression and a trigger for the condition. Depression and sleep often exist in a debilitating cycle, each making the other worse. Insomnia is common among women (and men) who are depressed, and so is oversleeping or sleeping at the wrong times, which makes routine nighttime rest more difficult.
Stress is also a trigger for upsetting your sleep cycle. Our brains are unsettled, anxiety begins to rise, and, as a result, our circadian rhythms can be disrupted.
An essential step in taking care of your well-being is being proactive about your sleep habits and making sure that you get enough sound sleep. The importance of sleep cannot be overemphasized; sufficient sleep on a regular basis has the power to revitalize the brain, rebalance hormones, and restore your overall physiological, mental, and emotional functioning.
Stress is a major contributor to disease risk, weakening immune function and leaving you more vulnerable to getting sick. Stress is rampant in our society, and loss of estrogen makes you even more vulnerable to stress. Regardless of your present situation—married or single, caring for children or empty nester, managing a career or working part-time—you are more than likely trying to manage a full, demanding schedule. I can’t bring to mind one patient of mine who does not have a constant, chronic amount of stress in her life. And although I cannot give advice on how to mitigate the individual sources of this stress, I can and do offer advice on how to better manage the stress so that it doesn’t create disease and steal your health.
Oftentimes, my patients are not fully aware of the impact of stress on their physical and mental health. Indeed, the feeling of heightened tension, of the need for action and response under fire, can drain the body and mind of energy and wear down your immune system. Over time, this state of high alert—the physical manifestation of stress—erodes physiological health right down to the cellular level.
I know from firsthand experience the toll that stress can take. I used to work 120 hours a week in practice, never stopping, always exhausted, trying to meet and keep up with my family and professional demands. I, too, had to make meaningful changes to my lifestyle so that I could experience more balance and peace of mind. For you, this balance is of huge importance.
Stress causes a cascade of problems that undermines your ability to experience pleasure, to enjoy activities, relationships, and work. I think of stress as a sinister, very adept, and skillful thief: under the cloak of being productive and measuring up, stress steals your rest, joy, health, and vitality. At a biological level, stress interferes with hormone function and balance, diminishes cognitive function, and threatens the structural health of the brain. Stress exacerbates mood disorders, disrupts emotional balance and processing, and wears away at emotional resilience. To be blunt: stress ages you.
At a neurobiological level, stress is the consequence of the brain and body’s response to perceived threat. That threat can be real (a car veering toward you in oncoming traffic) or perceived (the anticipation of a difficult conversation with your spouse). The brain-body knows no difference between actual threats and possible or perceived threats. Its response is the same, whether you are fretting while paying bills, nervously thinking about a job interview, or running from a bear. Whatever threat looms, the brain’s hypothalamus signals the pituitary and adrenal glands to release the hormone cortisol. This hormone supplies you with heightened attention and vigilance, immediate energy to marshal a physical response—to fight or to flee. When this physiological response—designed to protect you from immediate and serious harm—occurs frequently enough, over time it damages the body at the cellular level. The damage affects every organ, every tissue, every physiological function—and makes you vastly more vulnerable to disease.
The exhaustion and depletion that results from stress leaves you increasingly vulnerable to more stress. Under chronic stress, your cortisol levels are consistently elevated and your adrenal glands are perpetually overworked. Eventually, the adrenal system stops functioning properly—it physically exhausts itself. At that point, the adrenal system can no longer operate at full, normal capacity, and the body has reached a condition of adrenal fatigue or exhaustion. Cortisol levels drop—the adrenal gland can no longer produce cortisol in abundance, even in response to highly stressful triggers. In a state of adrenal exhaustion, your energy levels plummet, you feel a deep and pervasive fatigue, and you have trouble functioning during the day and difficulty sleeping at night. A daily routine that once felt manageable and even enjoyable may now feel like an insurmountable effort. Severe adrenal depletion can, in rare cases, lead to Addison’s disease, a life-threatening condition.
Estrogen is one of several hormones that, when in healthy, abundant supply, helps protect you from stress and its harmful consequences.
Cortisol: The Stress Hormone
Cortisol serves important metabolic and immunological functions, but, when chronically elevated, cortisol can cause physiological damage and increase risk for disease. Excessive cortisol
Migraines and other forms of debilitating headaches occur more frequently among women than men. Women are three times more likely than men to experience migraines, and roughly 30 percent of women will suffer from one at some point in their lifetime. Migraine headaches are tremendously painful, often paralyzing, and temporarily disabling to normal life. Intense pressure, stabbing, and throbbing pain (in many cases localized to the temples) are often accompanied by nausea and vomiting, numbness in the extremities, and extreme sensitivity to light, sound, and smell. Many migraine sufferers experience visual disturbances, including flashing lights, blind spots, and blurred vision.
Levels of estrogen and other hormones are an important factor in a woman’s risk of developing migraines. (Other significant factors are stress and lack of sleep, which are affected by both the presence of estrogen and estrogen deficiency.) When estrogen declines during the monthly cycle, you become more vulnerable to developing migraines or other severe, debilitating headaches. Once girls begin menstruating, they are more likely to get migraines. Migraines are most likely to occur in the week before your period, when estrogen is falling, and during menstruation, when estrogen is at its lowest. However, some women experience milder forms of migraines over the course of a month, when estrogen drops even slightly. Estrogen—specifically estradiol (E2)—acts as an anti-hyperalgesic, which means it lessens one’s sensitivity to pain.
Progesterone can also be a factor in migraine onset for women. Falling progesterone and falling estrogen together can trigger migraines during the premenstrual week. Migraines that occur during menstruation itself are more likely to be the result of low estrogen.
For women with a history of migraine, pregnancy—with its soaring estrogens—can be a respite from these difficult headaches. But immediately after childbirth, a woman’s body undergoes an abrupt, dramatic drop in estrogen, which can trigger a recurrence of migraines.
Perimenopause often brings an increase in migraines as a consequence of the irregular, often abrupt fluctuations of estrogen amid the hormone’s overall decline. Migraines continue to be more frequent and severe for women during menopause itself. As menopause progresses and estrogen levels stabilize, the incidence of migraine may lessen and quiet.
Women are especially vulnerable to bone loss and osteoporosis as they age, and estrogen acts as an antioxidant and anti-inflammatory, playing a vital role in slowing bone loss. Estrogen and other hormone deficiencies increase your risk for osteoporosis. Women become more vulnerable to bone loss and osteoporosis during menopause, when estrogen levels decline. Women who use low-dose estrogen birth control are also at particular risk for bone loss and osteoporosis, since they have a perpetual deficit of estrogen. (The progestin-only birth control Depo-Provera is also a factor in osteoporosis.) Antidepressant SSRI medications contribute to the risk for osteoporosis; maintaining estrogen levels guards against depression and reduces the need for these medications. When you get into a state of chronic low estrogen, you are vulnerable to weakening bones and muscle tissue because estrogen helps maintain lean muscle mass and also helps in muscle healing.
Please keep in mind that many emotional or behavioral symptoms, such as anxiety, depression, or sleep disturbances, can have causes other than hormonal ones. The same is true for certain autoimmune illnesses, such as thyroid disorders (Graves’ disease or Hashimoto’s), osteopenia, diabetes, and cardiovascular disease, which have multiple causes that come together to wreak havoc on your body. Chronic stress, for instance, can have a cascade effect on multiple parts of your brain and body. These overlapping, interacting systems are exactly why I practice integrative medicine; by looking at your body and brain as a whole, I can more easily assess your underlying issues so that you can address problems directly. Your hormonal health is one way to understand how to both protect your health and ward off disease, but there are many other systems at play in preserving your brain and body wellness.
YOUR HEALTH JOURNAL: CHECK YOUR MEDICINE CABINET
This is a good time for you to take note of all your current medicines, as well as any other prescriptions—for antibiotics, for instance—that you have taken in the last twelve months. Make a list of these medicines in your journal, since it will be important information for your doctor to consider.