Hormone replacement therapy with estrogen and progestin does not affect risk of stroke in postmenopausal women with heart disease, according to a large clinical trial published by researchers at University of California, San Francisco and San Francisco Veterans Affairs Medical Center.
Hormone therapy neither increased nor decreased the risk of stroke among these women, nor did it affect their risk of a transient ischemic attack (TIA), a blood clot in the brain that causes temporary stroke symptoms, said Joel Simon, MD, MPH, the study's lead author, a physician at SFVAMC, and UCSF assistant professor of medicine and epidemiology.
"This is the first clinical trial of hormone therapy to examine whether such therapy affects the risk of stroke. The bottom line is that the decision to use or not use hormone therapy should be based on its known risks and benefits, and not on any presumed effect on stroke risk," Simon said.
Previous studies that assessed the therapy's stroke risk had yielded mixed results. Some showed a benefit, some found no benefit, and the highly regarded Framingham Heart Study suggested an increased risk of stroke, at least among non-smokers. None of these studies, however, were randomized, controlled clinical trials.
Basic research has also found conflicting evidence for the effects of hormone therapy on stroke, Simon said. Estrogen is known to increase blood clotting, which hypothetically could increase risk of stroke. However, it also can cause beneficial changes in cholesterol - raising HDL cholesterol levels and lowering LDL cholesterol.
Stroke is the third leading cause of death in the US, according to the American Heart Association. A large proportion of these deaths are among older women, many of whom use the estrogen-progestin combination to treat the symptoms of menopause and for the prevention of osteoporosis.
The study is an analysis of data from the HERS (Heart & Estrogen-progestin Replacement Study). In 1993 and 1994, HERS researchers enrolled 2,763 postmenopausal women with heart disease. Over a four-year period, half the women received the estrogen-progestin combination, the most common type of hormone therapy taken by women in the US, and the other half took a placebo.
HERS' primary goal was to test whether estrogen plus progestin would prevent recurrent heart attacks in these women. The results, published in 1998, showed that hormone therapy increased heart attacks during the first year of the study, and then decreased them later on. At the end of the study hormones had no net effect on heart attack risk.
The stroke study found that although there was a slightly increased incidence of strokes among the women taking hormones, that difference was not statistically significant. "Such a small difference could have resulted by chance," Simon said.
He cautioned that the HERS findings may not apply to women taking estrogen without progestin or to postmenopausal women taking the combination therapy who do not have heart disease.
The findings are published in the latest issue of the journal Circulation.
The HERS results will not be the last word on the question of hormone therapy and stroke, Simon said. The large Women's Health Initiative will have data on hormone therapy in healthy women, and a similar trial is also underway in the United Kingdom, he said.
For their part, the HERS researchers will continue to follow the women who participated in the trial, as part of HERS II. "We have another two to three years of observations," Simon said. "We should be able to update this paper in another year or so to say whether these findings have changed."
Co-authors are Stephen B. Hulley, MD, chair and professor of UCSF department of epidemiology and biostatistics; Fran Harris, MS, and Josephine Fong, MS, statisticians in the UCSF department of epidemiology and biostatistics; Judith Hsia, MD, associate professor of medicine at George Washington University; Jane Cauley, DrPH, professor of epidemiology at University of Pittsburgh; Cynthia Richards, MD, Wyeth-Ayerst Research; Elizabeth Barrett-Connor, MD, professor in the department of family and preventive medicine at University of California, San Diego.