Estrogen Alone May Raise Dementia Risk

March 3, 2004

March 3, 2004

Hormone replacement therapy using estrogen alone in women who have had hysterectomies does not increase the risk of breast cancer, but does raise the risk of stroke and possibly dementia in older women, the government concludes.

Doctors had long been hopeful that the female sex hormone estrogen, either alone or together with a related hormone called progestin, would offer an array of benefits for older women. For decades, women have used hormone replacement therapy to ease hot flashes and other symptoms of menopause. Doctors also thought that hormones might help women build stronger bones, ward off heart disease, and possibly protect the brain and memory against the ravages of Alzheimer’s.

Last year, a major study of combination hormone therapy, consisting of estrogen and progestin, found that the combination therapy carries an increased risk of heart attacks, strokes, and breast cancer, as well as an increased risk of dementia. Although the increased risks are small, women have been cautioned about the combination hormone therapy.

Researchers thought that estrogen alone might be safer than the combination treatment. Estrogen alone is available only to women who have had a hysterectomy. Other women are not prescribed estrogen without progesterone, or progestin, because it would place them at risk for uterine cancer. Combining estrogen and progestin protects the uterus from cancer caused by estrogen alone.

The present study, the Women’s Health Initiative, involved 11,000 women aged 50 to 79 who had had a hysterectomy. Half took estrogen, and the others took a placebo (a look-alike “dummy” pill). Estrogen alone did appear to carry some real risks. Among the findings:

  • Estrogen alone doesn’t appear to have beneficial effects for the brain in older women (nor does combination therapy). Preliminary data from this study found that women who took estrogen may even be at slightly increased risk of dementia or mild cognitive impairment, although more follow-up is needed. (A previous study suggested that the hormone combination might even increase the risk of Alzheimer’s and other forms of dementia.)
  • Surprisingly, in the present study, estrogen by itself increased the risk of stroke. For every 10,000 women taking the drug, 8 would be expected to have a stroke as a consequence of taking the hormone.
  • Furthermore, estrogen alone did not prevent heart disease–although it also carried no increased risks for the heart. However, it did not affect the risk for breast cancer. Estrogen-progestin, in contrast, has been shown to slightly increase the chances of having a heart attack or developing breast cancer.
  • Estrogen alone did benefit the bones. It reduced the risk of hip fractures, a common problem in older women with thinning bones. (It also relieves symptoms of menopause such as hot flashes.)

NIH scientists will continue to follow up women who were taking the hormones to gather additional health data. A subsequent report will analyze the specific effects of estrogen on the brain and its possible relation to dementia in greater depth.

Deciding whether to take or continue hormone therapy is a difficult choice for many older women, especially those who might benefit from the drugs. This study adds a new piece to the puzzle. Women should discuss these issues with their doctors.

For more information on hormone replacement therapy and Alzheimer’s disease, visit www.ALZinfo.org.

By www.ALZinfo.org.  The Alzheimer’s Information Site.  Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.


National Institutes of Health, March 2, 2004: “NIH Asks Participants in Women’s Health Initiative Estrogen-Alone Study to Stop Study Pills, Begin Follow-up Phase.” Statement from Barbara Alving, M.D., Director of the Women’s Health Initiative and Acting Director of the National Heart, Lung, and Blood Institute.


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