Hormone therapy appears to boost dementia risk in women over age 65

June 22, 2004

CHAPEL HILL – By taking replacement estrogen, postmenopausal women over age 65 appear to raise their risk of developing dementia by a small amount rather than reducing it as earlier research had suggested, a new national study shows.Another closely related finding from the clinical trial indicates that estrogen use also mildly adversely affects the thinking ability scientists call global cognition in a small percentage of such women.The companion reports, published in the June 23 issue of the Journal of the American Medical Association, are part of the multi-center Women’s Health Initiative Memory Study, which is itself part of the much larger national Women’s Health Initiative, a long-term attempt involving some 27,000 volunteers to answer some of the most important lingering questions about ways of improving women’s health.

“We found that for every 10,000 women over age 65 taking a single replacement estrogen there would be 12 cases of dementia that otherwise would not have occurred,” said Carol Murphy, principal investigator of the WHI Memory Study at the University of North Carolina at Chapel Hill. “Among women over 65 taking combined hormone therapy, there would be 23 additional cases.”

“What this means is that there is no longer any indication at all for women of this age or older to take estrogens on a long-term basis,” said Dr. Gerardo Heiss, professor of epidemiology at the UNC School of Public Health and principal investigator for UNC’s WHI center. “The only indication for hormone replacement therapy appears to be short-term use in women experiencing the unpleasant symptoms commonly associated with menopause.”

Overall principal investigators for the dementia and global cognition studies are Drs. Sally A. Shumaker and Mark A. Espeland, respectively, both of the Wake Forest University School of Medicine. Volunteers received either estrogen hormones or placebos and were tested for mental functioning.

“This was the most comprehensive, careful study ever done testing whether the most common forms of hormone therapy reduced the risks of dementia,” Murphy said. “The trial with estrogen alone involved 2,947 women and a trial of a combined therapy of estrogen plus progestin involved 4,532. Two hundred and fifty-eight of the volunteers were screened through the UNC center, one of 39 across the nation.”

Murphy said the new findings were a disappointment.

“Previous work had suggested there was a benefit to estrogen for older women,” she said. “We found no evidence of that, and indeed found just the opposite. The increased risk of dementia for any individual woman was very small. However, from a public health standpoint, we don’t want to create cases that would not have happened without the therapy.”

The combined estrogen and progestin trials ended early in July of 2002 when scientists discovered adverse effects such as raising the risk of strokes, Murphy said.

In an accompanying editorial, Dr. Lon S. Schneider of the University of Southern California wrote that questions remain regarding taking estrogen during and after menopause.

“Most important is whether short-term use of estrogen over several years in early post-menopause is effective in reducing dementia two or three decades later,” Schneider wrote. “This is the crux of the observational data, suggesting that previous hormone therapy during a critical period is protective while recent or current use is not. By initiating hormone therapy at an approximate mean age of 71 years and following up patients to four to five years, WHIMS is intervening fairly late in life while seeking to identify relatively infrequent earlier-onset Alzheimer disease cases around age 75 years.

“The WHIMS results do not prove that estrogen therapy has no effect on Alzheimer disease or dementia, but they do clearly indicate that women older than 65 years should not be treated with conjugated equine estrogens with or without (progestin) to attempt to prevent dementia or enhance cognition,” he wrote.

Dementia is an age-related illness that impairs brain function. In 2000, more than 4 million U.S. residents had Alzheimer disease, a total expected to grow to 13 million by 2050. Milder cognitive impairment affects between 20 percent and 33 percent of older adults and strongly predicts dementia and institutionalization.

WHI researchers nationwide also are continuing to evaluate the potential benefits of low-fat diets on cancer prevention and calcium and vitamin D supplementation to prevent fractures in later life.

Details about menopausal hormone therapy are available at www.nhlbi.nih.gov . The National Cancer Institute, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Aging and the Office of Research on Women’s Health also support the Women’s Health Initiative investigations.

This article was researched and written by David Williamson of UNC News Services.

Note: Murphy can be reached at (919) 560-5606 (or 5607), Heiss at (919) 962-3253, Shumaker and Espeland at (336) 716-4453 and Schneider at (323) 442-2830.

UNC News Services contact: David Williamson, (919) 962-8596