According to new findings from a memory substudy of the Women's Health Initiative (WHI), older women taking combination hormone therapy had twice the rate of dementia, including Alzheimer's disease (AD), compared with women who did not take the medication. The research, part of the Women's Health Initiative Memory Study (WHIMS) found the heightened risk of developing dementia in a study of women 65 and older taking Prempro, a particular form of estrogen plus progestin hormone therapy.

The study also found that the combination therapy did not protect against the development of Mild Cognitive Impairment, or MCI, a form of cognitive decline less severe than dementia.

"Because of possible harm in some areas and lack of a demonstrated benefit in others, we have concluded that combination hormone therapy should not be prescribed at this time for older, postmenopausal women to maintain or improve cognitive function," says Judith A. Salerno, Deputy Director of the National Institute on Aging (NIA) at the National Institutes of Health (NIH), U.S. Department of Health and Human Services.

The memory substudy WHIMS was funded by Wyeth Pharmaceuticals, which manufactures Prempro, which it provided for use in the WHI trials. The larger WHI trials are supported by the National Heart, Lung, and Blood Institute (NHLBI) of the NIH. The NIA has been involved in reviewing the current findings as the NIH's lead institute on age-related memory change and dementia.

Importantly, the women in the combined estrogen plus progestin arm of the WHI and substudies such as WHIMS are no longer taking the combination therapy as part of the research trials. In July 2002, all combination therapy components of the WHI were halted when it was found that increased risk of breast cancer, heart disease, stroke, and blood clots among participating women on combined estrogen plus progestin therapy outweighed benefits for hip fractures and colorectal cancer.

The current findings address combined estrogen plus progestin therapy, specifically Prempro, among women 65 years of age and older. For younger women, the cognitive risks and benefits of this combination therapy are unknown. Short-term hormone therapy in younger women for some symptoms of menopause has been approved by the U.S. Food and Drug Administration and the new findings do not directly address decisions about such treatment. Researchers and officials at the NIH suggest that women of any age consult with a physician about their individual risks and benefits.

About 4,500 women participated in the WHIMS substudy of women 65 and older. Once the women met the criteria for participation, including screening tests to make sure they did not have dementia at the study's start, they were randomly assigned to take estrogen plus progestin therapy (one pill per day of conjugated equine estrogen (CEE), 0.625 mg, plus medroxyprogesterone acetate (MPA), 2.5 mg -- brand name Prempro or a look-alike placebo. Cognitive status was evaluated annually, and women who showed signsof decline were examined in greater depth to further characterize their cognitive status.

The researchers looked at several other factors that might influence cognitive status, including socioeconomic status, educational attainment, prior estrogen or progestin use history, and use of cholesterol lowering medications or aspirin or other non-steroidal anti-inflammatory drugs. These factors were not significantly different between the therapy group and the placebo group and did not account for the differences in rates of cognitive decline, the researchers said.