Combination Hormone Replacement Therapy Doubles Dementia Risk Report Researchers at Wake Forest University Baptist Medical Center

May 27, 2003

Older women who take the most common form of hormone replacement therapy (combined estrogen plus progestin) may double their risk of developing dementia according to research reported by Wake Forest University Baptist Medical Center researchers in this week’s issue of the Journal of the American Medical Association.

“The Women’s Health Initiative Memory Study (WHIMS) is the most comprehensive and rigorous study to date to test whether estrogen plus progestin would reduce the risk of dementia in older women,” said Sally A. Shumaker, Ph.D., the national principal investigator and a professor of public health sciences at Wake Forest. “Because of the potential harm and lack of benefit found, we recommend that older postmenopausal women not take the combination hormone therapy to prevent dementia and we hope that doctors will incorporate what we’ve learned in their recommendations to women.”

The WHIMS study, a sub-study within the Women’s Health Initiative (WHI), found that combination hormone therapy (0.625 milligrams a day of conjugated equine estrogen plus 2.5 milligrams per day of medroxyprogesterone acetate) doubled the risk for probable dementia in women 65 and older and did not prevent mild cognitive impairment.

Translated to a population of 10,000 women taking the combined hormone therapy, there would be an additional 23 cases of dementia per year.

“The overall individual risk to women is low, although there is reason for concern,” said Shumaker.

The study involved 4,532 postmenopausal women age 65 and older who were followed for an average of 4.05 years at 39 of the 40 WHI clinical centers.

Almost half (2,229) of the women received a daily tablet of the combination estrogen plus progestin, marketed as Prempro™, and the other women (2,303) received a placebo or “inactive” drug.

Dementia occurs when memory, judgment and thinking ability declines substantially to the point that it interferes with basic day-to-day activities. Alzheimer’s disease was the most common form of dementia found among the study groups.

Women in the WHIMS study, like women in the larger WHI study, stopped taking the estrogen plus progestin therapy in July 2002 when it was found that the risks for developing breast cancer, strokes and cardiovascular disease outweighed the benefits. At that time, not all of the memory study data had been analyzed and the dementia risk had not been established.

In addition to evaluating the effects of the combination hormone therapy on dementia and mild cognitive impairment, the study also looked at global cognitive function including concentration, language, memory and abstract reasoning.

In this area, women taking the estrogen plus progestin therapy performed slightly worse than the placebo group.

“What’s important is that these results paint a consistent picture with those for dementia by reinforcing the fact that estrogen plus progestin was not beneficial when compared to placebo,” said Stephen R. Rapp, Ph.D., professor of psychiatry and behavioral medicine at Wake Forest.

Women in the combination hormone therapy study arm continue to be followed and the WHIMS investigators continue to look at estrogen alone on the risk of dementia.

Additional information about hormone replacement therapy and dementia can be found at,, or

The study was funded by Wyeth Pharmaceuticals and the National Institutes of Health.


Media Contacts

Wake Forest: Barbara Hahn, (; Karen Richardson, (; or Mark Wright, ( at (336) 716-4587.

NIH: or Office of Communications 301-496-1752

Broadcast Editors: Video and audio clips of Dr. Shumaker are available at

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