Hormone replacement therapy does not appear to have any effect on stroke prevention in postmenopausal women who already have heart disease, according to a new study published in the February 6 issue of the journal Circulation.

Many studies have produced inconsistent results on the effect of postmenopausal hormone therapy on heart and stroke prevention. In the first clinical trial that examined this issue, researchers found that estrogen-progestin hormone replacement therapy did not alter the risk of stroke in postmenopausal women who have heart disease.

"Our findings indicate that there is no significant association between postmenopausal hormone therapy and the risk of stroke among postmenopausal women with heart disease," says lead author Joel Simon MD, a scientist at the University of California at San Francisco, and a physician at the Veterans Affairs Medical Center in San Francisco, California.

Researchers studied 2,763 postmenopausal women with known heart disease in the Heart & Estrogen-Progestin Replacement Study, dubbed HERS trial, which was conducted at 20 medical centers across the United States. Half the women received the estrogen杙rogestin combination and half took a placebo. The women, who averaged 66 years old, were followed for an average of 4.1 years. By the end of HERS, 7% of the women on the hormone therapy suffered a stroke compared to 5% of those receiving placebo, which was not a statistically significant difference, according to researchers.

The original HERS trial set out to examine whether the estrogen rogestin combination would prevent a recurrent heart attack. The results showed that hormone therapy did not have any significant effect, and they were published in 1998. But the secondary goal of HERS trial was to determine the therapy impact on stroke and transient ischemic attacks, known as TIA or "ministrokes." Again, researchers failed to find any significant effect of hormone therapy in stroke prevention.

Suzanne Oparil, MD, who wrote an editorial accompanying the study, says that she was not surprised at the findings, which confirmed some of the observational results that hormone replacement therapy does not have an effect on stroke prevention.

"From this study, hormones are not harmful but are not helpful either in stroke prevention, if you are postmenopausal and have heart disease," says Oparil, director of vascular biology and hypertension program at the University of Alabama at Birmingham, who is also a professor of medicine, physiology and biophysics. "Women should be aware that taking hormone is not a substitute for proper cardiovascular care. They should pay attention to their other risk factors such as blood pressure and cholesterol."

Todd Tolbert, MD, a cardiology fellow at the UAB who also penned the editorial, says he's concerned that estrogen's role in primary care is not clear. "The key question is --will estrogen be beneficial for women at menopause who do not have prior heart disease, or stroke?" asksTolbert. "Will taking estrogen at that time prevent or delay the onset of heart disease or stroke?"

Tolbert says that animal studies have clearly shown estrogen's beneficial effect in preventing some of the detrimental vascular response to injury. He also points out that the majority of the observational studies seem to be in favor of estrogen in terms of coronary prevention. "It is too early to eliminate the idea of estrogen replacement therapy as being beneficial for the prevention of cardiovascular disease," says Tolbert.

Tolbert cautions that research in this area is still ongoing. One of the largest studies, the Women's Initiative Study, will yield results in 3 to 4 years. "By then, there will be a clear picture of who should be taking estrogen and who should not," says Tolbert.

But now, there is not enough information to tell women who are taking estrogen to stop taking it, Tolbert explains. "If they are on it, and have been on it, I would continue the therapy. However, I would not start women on estrogen if my goal were to prevent cardiovascular disease or stroke. There are many other reasons to take estrogen for its benefits, for example, it is beneficial on bone metabolism."

Researchers also caution 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.

According to the American Heart Association, stroke is a leading cause of death and disability, particularly among older women, many who use the estrogen杙rogestin combination to treat the symptoms of menopause and to prevent osteoporosis.

© 2001 by Medscape Inc. All rights reserved.