The Female Brain (26 page)

The lack of joy in life, in the absence of any real-life tragedy, may be caused by low estrogen in the brain, which in turn decreases neurochemicals such as the mood-elevating serotonin, norepinephrine, and dopamine. Irritability, lack of mental focus, and fatigue can be caused by low estrogen and made worse by lack of sleep. A major problem for many perimenopausal women is sleep—either with or without hot flashes. There’s no time in your life when it’s healthy to go without adequate sleep, but this is especially true when you’re over age forty. Sleep is an essential renewing treatment for the brain. Unfortunately, erratic estrogen changes during perimenopause can disturb the female brain’s sleep clock. If you don’t sleep well for several days, it can be hard to concentrate; you may also become more impulsive and irritable than usual and say things you wish you hadn’t. So this may actually be a good time to bite your tongue in order to protect relationships. All these symptoms of the perimenopause in my experience can usually be treated with a combination of estrogen, antidepressants, exercise, diet, sleep, and supportive or cognitive therapy.

Once a woman has officially passed through menopause, her brain has started readjusting to low estrogen. For most women, the disruptive symptoms of perimenopause now begin to abate, though a percentage of women, unfortunately, suffer for another five years or more. Fatigue, mood changes, interrupted sleep, “mental fog,” and memory changes occur for some women, and more than about 15 percent still have hot flashes a decade or more past menopause. Some three out of ten postmenopausal women suffer from periods of low mood and depression, and up to eight out of ten experience fatigue. (All women with fatigue should have their thyroid checked.) Some studies, but not all, found that age-related cognitive functions, such as short-term memory, decline more quickly in the first five years after menopause.

In most cases, the female brain acclimates to lower levels of estrogen as the ovaries gradually retire. If a premenopausal woman has surgery to remove her uterus and ovaries, however, she’ll plunge into menopause with no transition. The sudden loss of estrogen, as well as testosterone, can trigger symptoms including low energy, low self-esteem, and low libido, as well as severe mood and sleep changes along with hot flashes. Most women who have total hysterectomies can avoid these problems if they start on estrogen replacement therapy in the recovery room or even before surgery. Early treatment with estrogen can be especially important to protect memory function posthysterectomy, as Barbara Sherwin’s studies have suggested.

Should I take hormones for my brain, and what can I do to reduce my risk of stroke and breast cancer if I do?

Most doctors now feel that each woman should let her own symptoms at menopause or perimenopause be her guide. For many women, HT, especially with continuous estrogen, helps stabilize mood and improves mental focus and memory. Some women say estrogen therapy gives them back their sharp minds and makes them feel smart again. Other women report unpleasant side effects, such as menstrual bleeding, cramping, breast tenderness, and weight gain, which may cause them to discontinue the therapy.

So what’s the best advice to date on HT? The Food and Drug Administration now recommends that women with menopause symptoms take the lowest dose of hormones for the shortest time possible, since scientists assume that lower doses are likely to be safer. The position statement by the Executive Committee of the International Menopause Society recommends that doctors not change their previous practices in prescribing hormone therapy to women at menopause or stop HT in any woman who is doing well on it because the WHI and WHIMS did not study women during the menopausal transition. Some American scientists, such as Fred Naftolin of Yale, are quite worried that doctors are now denying women the chance to take estrogen for prevention before it’s too late. He says,

So…these menopausal symptoms are warnings of estrogen deficiency [that are] singing out to alert us of the need to test the idea of prevention by timely estrogen treatment. We must rethink the current American position on prevention of menopausal complications by estrogen and thereby afford women the [treatment and] scientific rigor that they deserve.

Some studies indicate that if you are more than six years past menopause you have lost your window for prevention and should not start HT. Bottom line, every woman needs to discuss her personal risks and benefits with a doctor who specializes in hormone therapies. Rogerio Lobo, an expert for thirty years in HT, states that “the appropriate use of hormones largely alleviates concerns about the increased risk of cardiovascular (CV) disease and breast cancer. The appropriate use of hormones pertains to treating younger, healthy women who have menopausal symptoms as well as using low-doses of hormones and switching to estrogen-only therapy whenever possible.”

If you’re suffering from symptoms that are disrupting your quality of life, you may want to consider a few years of hormones to ease your brain through this transition. It’s not a moral issue; you’re not a weak person if you happen to be in the large group of women who need some medical help to be their best selves during this hormonal transition. And don’t feel that you’re making a decision today that will commit you to a particular treatment over the next forty years. You may want to continue HT after you get through the menopause transition, and you may not. Many new scientific discoveries and products regularly become available, and the race is on in the drug industry to develop estrogen-like drugs that help the brain and the bones without posing a risk to women’s breasts, heart, uterus, and vascular system. There are also many nonhormonal and alternative medicines and treatments that can be very helpful—including exercise, SSRIs, soy, high-protein/ low-calorie diet, vitamins E and B-complex, acupuncture, stress reduction, and meditation practice. The smart thing to do is keep informed and reevaluate your decision every twelve months.

If you do decide to take HT, be prepared for a period of trial and error. Responses vary greatly, so you’ll have to test-drive different treatments in your own body. Some HT doctors like to start with bioidentical hormones, which are most like the ones your own ovaries produce. If for some reason these don’t help you feel better, you should discuss other types of hormones; some women feel better on synthetic hormones or on patches, pills, gels, injectables, or pellets. If you still don’t feel good or better, don’t give up. Ask your doctor about alternatives or additions to hormones to treat your symptoms for the next year or two, including prescription serotonin drugs such as Effexor, Zoloft, or Prozac, herbal treatments, or exercise and relaxation therapies. The fact is, you know your own body best. Let your own symptoms be your guide. Above all, since new research is constantly emerging, plan to discuss whatever treatment you’re currently using every year with your doctor—it’s a good idea to set your appointment around your birthday so you won’t forget.

One of the major reasons scientists believe women in the WHI and WHIMS who took HT had somewhat more stroke, dementia, and heart attacks was that taking estrogen on top of already clogged and aging blood vessels makes matters for the heart’s and brain’s blood vessels worse—especially since many of these women were smokers. If you decide to take hormone therapy, keep your blood pressure low, don’t smoke, get at least sixty minutes per week of increased-pulse cardiovascular exercise, keep your cholesterol low, eat as many vegetables as you can, take vitamins, decrease your stress, and increase your social support.

Weight gain, not brain functioning, is actually the biggest concern many women express about HT and the major reason they give worldwide for stopping the treatment. The hypothalamus controls our appetite. Since many of the changes during the menopause happen in this area of the brain, some scientists have speculated that the appetite-controlling cells are adversely affected by declining estrogen. To test whether weight gain was caused by HT, researchers in Norway studied ten thousand women ages forty-five to sixty-five who were and were not on hormone therapy. Their results showed that weight gain is not linked to HT. Instead they found that changes in a woman’s diet and physical activity, both of which may have to do with changes in her hypothalamus at menopause, are the cause of weight gain.

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Estrogen-only therapy, without progesterone, it’s important to note, is appropriate only for postmenopausal women who’ve had hysterectomies. It’s not the same as hormone replacement therapy (HT), with progesterone, which is prescribed for women who still have a uterus. There’s an important difference: HT with progesterone keeps estrogen from building up the uterine lining and possibly producing cancer cells. Progesterone can be taken in pill form combined with estrogen or as an intrauterine device with progesterone or vaginal gel. Progesterone, however, seems to counter some of the positive effects of estrogen in the female brain. Just as progesterone reverses the growth of unwanted cells in the uterus, it seems to reverse some of the growth of new connections in the brain. As a result, the brain benefits of HT with progesterone are a matter of controversy. If a woman is able to take estrogen alone because she has no uterus, she can get all the benefits of estrogen she had at the best part of her menstrual cycle—all the time, but without the PMS-causing progesterone. Some women who do not tolerate progesterone but still have a uterus can have annual removals of their uterine lining through a procedure called dilation and curettage (D & C) or endometrial ablation. They can also get annual vaginal ultrasounds of the uterine lining to make sure it isn’t growing. Women taking the lowest doses of estrogen HT do not usually need to take progesterone even if they still have a uterus.

It’s not until many years after menopause that the natural processes of aging start having a noticeable effect on the functioning of the female brain. Some memory decline does start as early as age fifty, but it is usually not bothersome. Hormone therapy may or may not help slow it down. Many of these aging processes involve decreased blood supply and a breakdown in the body’s ability to repair damage.

It is now clear that estrogen keeps blood vessels in the brain healthy. Researchers at the University of California, Irvine, found that estrogen did this by increasing the efficiency of the mitochondria in the brain’s blood vessels, perhaps explaining why premenopausal women have lower rates of stroke than men their age. Research at Children’s Hospital in Pittsburgh, Pennsylvania, also discovered a sex difference in the way brain cells die after injury. Levels of glutathione, a molecule that helps brain cells survive oxygen deprivation, remain stable in females after a brain injury, but they drop up to 80 percent in males, resulting in greater brain cell death. It may be that male and female brain cells die in different ways following established sex-specific biological patterns and pathways that may be related to why women live longer than men.

Sex differences appear in other aging processes, too. Estrogen and progesterone, for example, seem to help repair and maintain the connecting cables between brain areas. As our brains age and our bodies stop repairing these connections, we lose white matter, and our brains process and send information more slowly or not at all. As a result, some signals get weaker, changing the pathways, patterns, and speed in our aging brains.

One process that often slows down noticeably is memory retrieval. This is common in the older brain even though no specific disease or dementia is present. Alzheimer’s is one of a group of dementia diseases that gradually destroy brain cells and impair mental function. Alzheimer’s makes sticky plaques in the brain, decreasing the ability of brain cells to communicate with one another and eventually killing them. Although men tend to be more vulnerable to age-related memory loss than women, postmenopausal women, it turns out, have three times more risk than men for developing Alzheimer’s disease. Scientists don’t yet understand this gender difference but suspect it may have to do with older men’s brains having more testosterone and estrogen than those of postmenopausal women who don’t take HT. Careful studies of the brains in an animal model of Alzheimer’s have shown deficient levels of estrogen. It remains a mystery, nevertheless, why women are more susceptible to this disease even after correcting for the fact that on average they live longer.

Studies indicate that starting estrogen replacement therapy early in menopause, when neurons are healthy, reduces the risk of Alzheimer’s disease. However, estrogen therapy initiated once the disease has developed or decades after menopause offers no benefit. Evidence from animal experiments and human studies also suggests that estrogen therapy may be able to delay dementia symptoms and brain aging in females. The idea that estrogen therapy may help prevent some cases of Alzheimer’s in women is an attractive one but remains to be proven.

For women—even those past menopause—staying socially connected and supported is an important way to reduce the stresses of living alone and getting older. Women respond to stress differently than do men and get more benefit from social support.

Many activities can counter the effects of aging on the brain. Researchers at Johns Hopkins University found that women and men over age sixty-five who had the widest variety of activities had the lowest rates of dementia. Physical exercise, such as walking and bike riding, helped, but so did mental exercises, such as playing cards. As our bodies age, it’s important to stay active on many levels, and it’s diversity, not intensity, that may be key.

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