Despite many observational studies linking hormone replacement therapy (HRT) to reduced risk of cardiovascular disease and possibly stroke, Yale researchers have found in a new study that HRT does not reduce the risk of a second stroke or death in women with cerebrovascular disease.
The team also found that HRT was associated with a borderline increase in the risk of fatal stroke.
"We have shown that estrogen replacement therapy for secondary stroke prevention is not beneficial," said study author Lawrence M. Brass, M.D., professor of neurology and in the Department of Epidemiology and Public Health at the Yale School of Medicine. "Conventional estrogen therapy really should not be used solely for stroke prevention. Women who were taking HRT for other reasons, such as bone loss prevention, can now make more informed decisions."
Published in the October 25 issue of the New England Journal of Medicine, the Women's Estrogen for Stroke Trial (WEST) began in 1993. The study was a randomized, placebo-controlled trial of estrogen for prevention of second strokes in 664 postmenopausal women. The women were an average of 71 years old and were recruited from 21 hospitals in the United States. The researchers followed the occurrence of stroke or death for a three-year period.
During the follow-up period, there were 99 strokes or deaths among the women randomized to the estradiol group, and 93 among those in the placebo group. The women who were randomly assigned to receive estrogen therapy had a borderline higher risk of fatal stroke and their nonfatal strokes were associated with slightly worse neurologic and functional deficits. The Yale team found no overall benefit to taking a standard dose of estradiol (1 mg a day).
"Our study is the first of its kind to look at the effects of HRT on post-menopausal women who have had a recent stroke," said first author Catherine M. Viscoli, research scientist at Yale School of Medicine.
A 1998 study of HRT for secondary prevention of heart attacks in post-menopausal women also found that estrogen was not beneficial. The Heart and Estrogen /Progestin Replacement Study (HERS) showed that hormone therapy did not reduce the incidence of heart attacks or death during four years of follow-up.
"It is hoped that the results of these studies will open up new lines of investigation that will help us understand why estrogen therapy did not work and allow us to better target a sub-group of women where estrogen may be beneficial," said Viscoli.
Brass said over half of all strokes occur in women and they account for nearly 60 percent of stroke-related deaths. Strokes are the third leading cause of death and the single leading cause of serious disability in adults. Of those who survive a stroke, 90 percent are left with some permanent disability and 40 percent require significant help with activities of daily living.
Other authors on the study include principal investigator Ralph I. Horwitz, M.D., The Harold H. Hines Jr. Professor of Internal Medicine and Epidemiology and Public Health, chair of internal medicine at the Yale School of Medicine, and chief of the Beeson Medical Service at Yale-New Haven Hospital; Walter N. Kernan, M.D., associate professor of internal medicine at Yale School of Medicine; Philip M. Sarrel, M.D., professor of psychiatry and obstetrics and gynecology at Yale; and Samy Suissa of McGill University in Montreal, Canada.
The study was funded by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health.
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