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The latest studies to question long-term use of hormone-replacement therapy conclude that the treatment not only fails to prevent mild memory problems in older women but actually increases their risk of dementia.

The findings published today in the Journal of the American Medical Association come as a surprise because they run counter to earlier research that suggested hormone-replacement therapy might provide protection against Alzheimer's disease and other causes of dementia.

The studies add to the disappointing results reported last year that older women who use hormone-replacement therapy for many years can harm their physical health.

Still, the message for women is not clear-cut.

Researchers, including those in Buffalo, said the findings show that older postmenopausal women should not take the therapy for dementia. But they said many women still might want to use the hormones for a short period to treat such menopause symptoms as hot flashes.

"It's important that women not panic. They need to discuss the therapy and research with their doctors and then make a decision," said Jean Wactawski-Wende, co-author of one of the studies and co-director of the University at Buffalo's Women's Health Initiative Vanguard Center.

Last year, scientists working on the Women's Health Initiative ended the nation's biggest study of a common type of hormone-replacement therapy, saying long-term use of estrogen combined with progestin significantly increases women's risk of breast cancer, strokes and heart attacks.

At the time of the study, 6 million women in the United States took estrogen and progestin for various reasons, including relief of menopausal symptoms and prevention of heart disease, brittle bones and memory loss.

Now, two sub-studies from the Women's Health Initiative show the therapy is no help for dementia. A third study in the journal offered further confirmation of last year's results for stroke, showing that hormone-replacement therapy increased the risk of a brain attack by 31 percent in postmenopausal women.

The Women's Health Initiative Memory Study involved 4,532 women who, on average, used Prempro, a brand of estrogen-progestin pills, for more than four years. It was funded in part by Prempro-maker Wyeth Pharmaceuticals.

Numbers small, but real

One study found that combination therapy doubled the risk of probable dementia and did not prevent less-severe mental decline.

At the close of the study, dementia was diagnosed in 61 women -- 40 among the 2,229 women taking the hormones compared with 21 among the 2,303 women who took a harmless substance. Researchers predicted an additional 23 cases of dementia a year for every 10,000 women on the therapy.

"The numbers are small, but they are real. Considering the millions of women who took the therapy, that's a lot of additional cases of dementia," said Dr. Jennifer Hays, co-author of the second similar dementia study and director of the Center for Women's Health at the Baylor College of Medicine in Houston.

For years, doctors have thought that hormone supplements might sharpen the mind.

Their belief was based on speculation that estrogen prevents cell damage and improves blood flow. In addition, previous studies suggested a lower risk of dementia for women taking estrogen compared with those not taking postmenopausal hormone therapy.

But the previous research consisted mainly of observational studies, in which participants lived their daily lives as they chose and then reported their results to researchers. Physicians don't consider observational studies as valid as controlled trials, in which scientists randomly assign patients to receive medical treatments and then analyze the results.

"The evidence for the therapy being beneficial for dementia was always very thin. The belief that it worked was based more on enthusiasm than real data," said Dr. Maurizio Trevisan, co-director of UB's Women's Health Initiative Vanguard Center.

Since 1993, about 4,000 Western New York women have been involved in the national study, and 151 of them took part in the memory study.

For some, risk worthwhile

Why might the therapy raise the risk of dementia?

One explanation is that hormones increase the risk of strokes, which are known to cause brain damage and contribute to dementia, the researchers said.

Although faith in hormone-replacement therapy has declined, doctors stress that older women should not abruptly stop taking it or rule it out as a treatment.

For some individuals, hormone therapy may be worth the risk for short-term relief of such miserable symptoms as hot flashes and night sweats.

"We face a problem in which many women with terrible symptoms are reluctant to take the therapy, yet may be helped if they use it for a short period," said Dr. Carlos Santos, a gynecologist with OB/GYN Associates of Western New York.

But many patients have grown accustomed to taking hormone-replacement therapy for 10 to 20 years.

"They don't want to stop," Santos said. "Now, they are going to have to make a difficult choice."

In some cases, Santos and others said, physicians can prescribe an alternative treatment.

Lowest dose, shortest use

Wyeth estimates that 1.2 million women continue to take Prempro pills, down from about 3.4 million before the study was halted last summer. Other types of hormone supplements include patches and creams.

Wyeth's Dr. Victoria Kusiak said whether the disappointing results would apply to the drug's typical user -- a younger woman with menopausal symptoms -- remained unclear. Still, she said the company agrees with doctors who say that hormones should be used only to treat menopause problems "for the shortest duration and the lowest dose."

One other study in the Women's Health Initiative is continuing to look at estrogen-only supplements and dementia in women who have had hysterectomies. Estrogen alone is not recommended for women with intact wombs because it increases the risk of uterine cancer.


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