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Might estrogen prevent memory loss?


Probably most of you have thought that it seems as if men and women think differently and are emotionally different. Indeed, the French expression vive la difference suggests much more than simply that men and women look different, but rather that the interaction of masculine and feminine behavior influences our everyday lives in subtle and interesting ways. Most of you have probably also heard the expression "sex is really in your head," implying that sexual fantasy and other higher cognitive and emotional factors are far more important in the human sexual response than the simple physiology of intercourse. And though we are all highly intellectual beings, I wonder if any of us do not go through a day without some sexual fantasy intruding on our thoughts.

Of course, reproduction is as essential to our species as it is to any other, and because our reproductive ability is generally determined by our behavior, would it really surprise you if I told you that human sexual fantasies may be influenced by such gonadal hormones as estrogen? For example, when adult women have their ovaries taken out for medical reasons, a precipitous loss of estrogens occurs. When these ovariectomized women are given oral estrogens to replace their lost estrogens, a significant increase in the frequency of sexual fantasies has been demonstrated. Now fantasy, or imagination, is certainly one of the most sophisticated of human thought processes, so that this is an example of how estrogens may influence human thought. But the effect of gonadal hormones on human thought and emotion may be even more pervasive and significant.

A list of masculine and feminine psychologic characteristics has been gathered from a number of scientific studies. Perhaps the most well recognized of these characteristics is that men have better spatial abilities for such tasks as putting together toy models, and women are better at verbal communication. In addition, men are more oriented to objects, and women are more concerned with people. And of course, we perceive men as generally more overtly aggressive. These differences in behavior are seen even in young children. Little boys, for example, seem to be always running around, while little girls are usually more sedate and calm. Indeed, recent research has shown that differences in the moods of boys and girls less than two years old correlate with their levels of sex hormones.

In fact, sexual differentiation of the brain begins during fetal development. Recent research indicates that, as in the development of the genitals, we begin fetal life with an essentially female brain. In males, under the influence of testosterone, the brain becomes defeminized, and then masculinized. The female continues to develop under the influence of estrogen. Estrogen and testosterone cause specific types of nerve cells to survive and grow, resulting in the development of the circuits in the brain responsible for sexual and other gender-related kinds of behavior.

Although human personality is complex and greatly influenced by society and culture, there appear to be subtle but essential gender differences in behavior in human beings, the result of the effect of gonadal hormones on the development and function of the brain. Although the modern feminist revolution may teach us to change some gender-related behavioral traits (one hopes for the betterment of the lives of both adult women and men), the effects of modern evolution do not negate what has been true since the beginning of mammalian life: that behavioral differentiation of the species according to sexual gender has a hormonal basis.

At the time of the menopause, women almost completely lose their estrogens, and this loss has significant consequences for the health of women, because estrogens also have an important effect on other organs of the body, such as the vagina, the bladder, and the bones.

The study of the menopause and the postmenopausal period of life has become enormously important. At present, there are 30 million postmenopausal women in the United States alone, and postmenopausal women are the most rapidly growing portion of our society.

This enormous population of postmenopausal women has no historical precedent. As recently as 1900, when the average life expectancy was about 40 years, few women lived beyond their reproductive years. And yet the modern woman can expect to live fully one-third of her life in the postmenopausal period. However, the long-term consequences of survival in the postmenopausal period without estrogen--a hormone essential for so many normal female functions--are just beginning to be understood.

The loss of estrogens at the menopause may result in both acute and chronic disease. At the time of the menopause, up to 80 percent of women experience "hot flashes," which may persist for up to ten years. These hot flashes have been shown to be real physiological events, with marked changes in blood flow and skin temperature. These hot flashes appear to result from changes in the part of the brain that regulates temperature control. Vaginal atrophy (causing painful intercourse) and urogenital atrophy (ultimately contributing to incontinence) can also result from the loss of estrogen at the menopause. After the long-term absence of estrogens, serious chronic diseases may occur, including osteoporosis. And recent data suggest that the loss of estrogen at the menopause may contribute to heart disease in postmenopausal women.

In addition to these diseases, normal menopause is often associated with psychologic symptoms: such emotional disturbances as depression, anxiety, and irritability, as well as such cognitive symptoms as memory loss and difficulty concentrating. The cause of these psychologic disturbances at the time of the menopause is not really known. Although grief associated with loss of reproductive capacity or the perceived onset of aging may contribute in psychodynamically predisposed women, psychologic symptoms may be the direct result of the loss of estrogen's effect on the brain.

Data from a number of well-controlled studies indicate that estrogen replacement therapy (ERT) relieves many of the psychologic symptoms during menopause, including depression and memory loss. However, the exact relationship between estrogen replacement therapy and these improvements is not known; much research is needed to further denite the role of psychodynamic factors and hormonal factors in the development of psychologic disorders during menopause.

One of the most common forms of brain disease in postmenopausal women is Alzheimer's disease. Alzheimer's disease is now the fourth most common cause of death in people over the age of 75. This disease, which occurs almost exclusively in the postmenopausal period, has recently been shown in most studies to be more common in women by nearly a two-to-one ratio.

Although we don't know the cause of Alzheimer's disease, we do have some clues. We know that specific core regions of the brain--called the nucleus basalis--degenerate, and that this degeneration appears to have widespread effects on cognitive and emotional function. At Rockefeller University, Dr. Victoria Luine, working with Dr. Bruce McEwen, a pioneer in the field of the effects of sex hormones on the brain, has shown that the functioning of a region in the brains of rats comparable to the nucleus basalis in humans may deteriorate after the ovaries are removed and may be restored by estrogen replacement therapy.

Studies of brains taken at autopsy from patients with Alzheimer's disease have shown that nerve cells degenerate during the course of the disease. Estrogens cause nerve cells to grow in a manner similar in appearance to the reverse of this process of degeneration. Estrogens have also been shown to protect nerve cells against certain kinds of injury. Thus, estrogens have an effect on the brain in two ways: They enhance the growth of nerve cells and influence their function.

As a geriatrician, a physician who specializes in the care of elderly people, I began working with Dr. McEwen's neuroendocrinology group at Rockefeller to understand the cause of Alzheimer's disease. We speculated that the loss of estrogens during the menopause might result in the dysfunction, atrophy, and death of brain cells that require estrogen for their normal function.

Because these estrogen-responsive neurons may have widespread and important effects on cognitive and emotional functioning in women, the appearance of psychologic symptoms during the menopause and postmenopausal period may have a neurobiologic foundation in basic studies on the effects of estrogen on nerve cells.

Thus, we wondered whether Alzheimer's disease in postmenopausal women might be the result of estrogen deficiency and whether postmenopausal Alzheimer's disease could be treated with ERT. At least one study has employed estrogen replacement for the treatment of psychologic dysfunction in elderly postmenopausal women. In a 1968 study by Herman Kantor and his colleagues in Dallas, Texas, elderly women in a nursing home were given estrogens or placebos, and their psychologic functioning was measured. After only three months, a significant difference between the two treatment groups was noted. After three years, while the placebo-treated group had deteriorated significantly, the estrogen-treated group maintained their psychologic functioning without deteriotation. These studies suggested that estrogen replacement therapy may prevent deterioration of psychologic functioning in elderly women.

About three years ago, our group at Rockefeller began to investigate whether estrogens could be employed for the treatment of Alzheimer's disease in postmenopausal women. These studies have been conducted at the Rockefeller University Hospital and Outpatient Clinic in New York City. With current diagnostic capabilities, physicians are able to diagnose Alzheimer's disease with about a 90 percent accuracy. We have found that postmenopausal women with Alzheimer's disease had significantly lower levels of estrogen in their blood when compared to the blood levels of estrogen in age- and weight-matched, normal women. Although these data support the hypothesis that Alzheimer's in postmenopausal women may be related to estrogen deficiency, we are currently seeking confirmation of these data in a larger group of patients.

We have given oral estrogen replacement therapy to postmenopausal women with Alzheimer's disease and have found beneficial results. Initially, we conducted an open trial in eight postmenopausal women with Alzheimer's disease to determine whether such therapy is effective, as well as safe. No serious side effects were encountered. After six weeks of therapy, half the women responded with improvements in cognitive and emotional functioning, as measured by standard psychologic testing. The women who responded to estrogen tended to be older, and they therefore had suffered more prolonged postmenopausal estrogen deficiency. Of interest, the women who responded to estrogen tended to have osteoporosis, another sign of long-term estrogen deficiency. Recent studies have been devoted to further investigating the relationship between the occurrence of osteoporosis and dementia in postmenopausal women.

These results have also been confirmed in a second study of oral ERT in a small number of postmenopausal women with Alzheimer's disease. Although these data support the idea that ERT is of value in the treatment of Alzheimer's disease, we do not recommend the widespread clinical use of estrogen for Alzheimer's disease until further research has proved without doubt that such therapy is both effective and safe.

In this regard, recent evidence indicates not only that the long-term use of ERT in postmenopausal women is safe, but that it may actually have a number of protective beneficial effects. Historically, widespread use of ERT was initiated during the 1950s employing regimens of estrogens without progesterone, which did not mimic the normal cycle of premenopausal women. As a result, in 1975, it was recognized that this method of ERT resulted in a high incidence of uterine cancer. This has become known as the "cancer scare." As a result, researchers around the world have studied the efficacy and safety of cyclical estrogen therapy with progesterone, which mimics the normal menstrual cycle.

Recent data suggest that, compared to the use of estrogens alone, or even to the use of no estrogens at all, the use of cyclical estrogen with progesterone during the postmenopausal period may actually prevent uterine cancer. In fact, the risk of death from uterine cancer, the most serious side effect of ERT, is 1 in 20,000 after years of treatment. And while the risk of death from an airplane flight is 1 in 10,000, the risk of death from hip fractures due to osteoporosis in elderly women who have not taken estrogen replacement therapy is 1 in 60.

Indeed, the risks of long-term postmenopausal ERT are probably far out-weighed by the benefits. Besides preventing osteoporosis, recent data suggest that long-term treatment of postmenopausal women with ERT may prevent heart disease.

And newer, safer forms of estrogens, such as the application of estrogen via the skin patch, which was recently approved for the long-term treatment of osteoporosis in postmenopausal women, will further reduce the side effects of estrogens.

In our modern era, we still need to learn more about the impact of estrogen deficiency in the postmenopausal period of life, a time that can be the crowning pinnacle of a woman's life and accomplishments, a time in which the modern woman will spend fully one-third of her life, a time when thinking clearly would never be more important.
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Title Annotation:loss of memory in postmenopausal women and Alzheimer patients
Author:Fillit, Howard M.
Publication:Saturday Evening Post
Date:Dec 1, 1986
Previous Article:Christmas and the family tree.
Next Article:Is an estrogen skin patch for you?

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