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Hormone Replacement Fails Again

In yet another blow to hormone replacement therapy (HRT), scientists have found that a combination pill containing estrogen and progestin fails to improve cognition or prevent dementia in older women and may even accelerate mental decline. The study, part of the massive Women's Health Initiative, eliminates one of the last hopes surrounding HRT, that it can improve or sustain brain function.

For decades, menopausal women and their doctors believed that estrogen and progestin could stave off various diseases associated with aging, including heart disease and dementia. Then last summer, researchers reported that Prempro, a popular combination pill, not only didn't protect against heart disease but actually increased that risk, as well as making breast cancer and stroke more likely (ScienceNOW, 9 July 2002). Still, some researchers held out hope that the drug would at least improve cognitive function, as suggested by a few smaller studies.

That hope has now been dashed. Reporting today in the Journal of the American Medical Association, a team of scientists from the Women's Health Initiative Memory Study (WHIMS), a subset of the larger Women's Health Initiative, report that Prempro provides no boost to cognition or protection against dementia in women 65 years of age and older. Nearly 4400 women participated in the study; roughly half were randomly assigned to receive Prempro, while the other half received a placebo. Neither group knew whether they were taking the drug.

Analyzing the WHIMS data revealed that "there is absolutely no evidence that estrogen plus progestin protects cognition," says Stephen Rapp, a psychologist at Wake Forest University School of Medicine in Winston-Salem, North Carolina, and the lead author of the study. Furthermore, researchers found that women taking the hormones had a 6.7% chance of suffering a "meaningful drop" in cognition from one year to the next, compared to 4.8% on the placebo; Rapp says there's no clear explanation for that effect. Thousands of women in a separate arm of the Women's Health Initiative continue to take estrogen alone, which has not been linked to serious health problems.

Phyllis Wise, a reproductive endocrinologist at the University of California, Davis, agrees that there's no doubt that Prempro doesn't stave off dementia. But she notes that progestin is thought to counteract the effects of estrogen on brain tissue and that estrogen taken by itself may yet be good for the brain.

Related sites
The Women's Health Initiative
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