Estrogen and Alzheimer's Disease

The role of estrogen in maintaining women's health is discussed frequently in the media. Recently, estrogen has received attention because studies have shown an association between the use of this hormone and a lowered risk of Alzheimer's disease (AD). AD is a brain disorder that over time results in irreversible memory loss, behavior and personality changes, and a decline in thinking abilities. Several large studies are exploring the relationship between estrogen and AD. It may be years, however, before the results of these studies will show whether or not estrogen can postpone the onset or slow the progression of AD.

What We Know So Far

At this time, there is no evidence to say that estrogen definitely can prevent AD. This means that we do not know yet whether doctors should recommend estrogen to women for preventing AD. The results of additional large clinical trials are needed before many questions about estrogen can be answered.

Studies to date on the relationship between estrogen and AD have been observational. They have suggested that women who had taken estrogen over time were less likely to have developed AD than those who had not taken estrogen. National Institute on Aging (NIA)-supported researchers at the Columbia Presbyterian Medical Center (CPMC) in New York City and NIA's Baltimore Longitudinal Study of Aging in Maryland have been looking at estrogen. These scientists found that women who took estrogen after menopause had lower rates of AD, or developed AD later in life, than those who never took it.

Researchers at the CPMC also found that among healthy women, those who used estrogen did better on mental function tests than those who had never used estrogen.

While these findings are encouraging, only controlled clinical trials will determine whether estrogen replacement therapy (ERT) can delay or prevent the onset of AD as well as the safety, dose, and duration of estrogen treatment needed to produce these effects.

Estrogen/Hormone Replacement Therapy

To replace hormones women lose after menopause, many doctors prescribe either estrogen replacement therapy (ERT) or hormone replacement therapy (HRT). ERT is estrogen alone for women who have had their uterus removed (hysterectomy). HRT is a mix of estrogen and progestin, a synthetic form of a hormone called progesterone.

Studies Now Under Way

Clinical trials are studies of a treatment's effects in humans. Clinical trials tell researchers if a promising treatment is safe and effective for patients and which among several treatments are more effective than others. In a double-blind clinical trial, volunteers, investigators, and data analysts do not know who is getting the test drug. Placebo-controlled means that some volunteers will receive an inactive substance.

NIA's Alzheimer's Disease Cooperative Study conducts AD clinical trials at a number of research centers. One of these studies is examining whether estrogen can slow the progression of AD. Participants taking estrogen will be followed over time, and their cognitive and other AD symptoms will be evaluated and compared to those of patients taking a placebo.

The National Institutes of Health is sponsoring the Women's Health Initiative (WHI) to study 70,000 women age 50 and older around the country. The WHI will assess the long-term benefits and risks of hormone replacement therapy (HRT) to prevent memory loss, heart disease, osteoporosis, and breast and uterine cancers. It is scheduled to end in the year 2005, and results are expected by 2007.

Focusing on estrogen's anti-oxidant effects, another NIA-supported research team is working to make an estrogen molecule safe for both men and women with AD or at risk for AD. These scientists hope that "designer" estrogen will delay or reduce AD's effects while avoiding some of estrogen's unwanted side effects, such as the development of feminine traits in men or increased risk of breast cancer in some women.

Researchers also are looking at plant-based estrogens, called phytoestrogens. Foods containing soybeans are especially rich in these plant estrogens. Interest in soy as a primary protein source has grown, in part because people who live in some Asian countries, where soybeans and their products are staple foods, have much lower rates of heart disease and certain cancers than do people in Western countries, where most people eat very few soy-rich foods. Further, Asian women report fewer menopausal symptoms such as hot flashes. Several studies are under way to understand how phytoestrogens work in animals and humans. Until studies can show benefits and risks, researchers recommend following a balanced diet.

What Women Can Do Now

Clearly, medical research has yet to answer all of the questions about estrogen and its possible uses in preventing or treating AD. Until more results are available, healthy women considering ERT/HRT should learn as much as they can about the benefits and risks of these treatments and consider their personal and family medical histories, including heart disease, stroke, osteoporosis, and breast cancer.

More information about menopause and ERT/HRT is available in the booklet, Menopause, and the pamphlet, Age Page–Hormone Replacement Therapy: Should You Take It? To request these free publications, contact the National Institute on Aging Information Center (NIAIC) at the address or telephone number listed at the end of this fact sheet.

Whether to use ERT/HRT is an important, complex decision that each woman can make with her doctor's help. At this time, women should base their ERT/HRT decisions on their overall health concerns, not solely on what is known about estrogen's possible effectiveness against AD.

Source: National Institute on Aging, National Institutes of Health, May 1998