Increased Stroke Risk With Combo HRT

But Estrogen-Only Effect Unclear

From the WebMD Archives

Feb. 14, 2003 --The hormone replacement researchers have finished dotting the i's and crossing the t's for the massive estrogen-progestin study that burst the hormone replacement bubble last summer and the news is still discouraging: Postmenopausal taking estrogen and progestin increase their risk for stroke by 33% compared with women who don't take hormones, regardless of whether there's a history of high blood pressure.

The Heart Lung and Blood Institute halted the study when it was discovered that postmenopausal women taking combination therapy -- estrogen plus progestin -- had an increased risk for breast cancer, heart disease, and stroke, which was equivalent to eight, seven, and eight more cases per 10,000 women respectively. But in that study, the average age at which the women were started on therapy was 63, although the optimal age is as close to menopause as possible.

At the time, the "overall increased risk for stroke was reported as 41% greater than postmenopausal women who were taking placebo," says Sylvia Wasserthiel-Smoller, PhD, professor of epidemiology and social medicine at the Albert Einstein College of Medicine, New York. Women who have a history of high blood pressure who took Prempro, the study drug, increased their risk for stroke by 40%, she says. In healthy women the stroke risk increased by 28%. Overall, the increased risk amounts to eight more strokes per year for every 10,000 women.

But Smoller, a principle investigator for the Women's Health Initiative Study, says the findings are still quite clear: Taking combination therapy is hazardous to the brain. She tells WebMD "given the choice between sweating and a stroke, I would recommend that women learn to tolerate the sweating." Nevertheless, HRT is indicated to relieve the symptoms of menopause.

Smoller adds, however, that the Women's Health Initiative is continuing another part of the study that is investigating the effect of estrogen alone on risk for stroke. "That part of the study is continuing so I want to be very clear that we have no final word on estrogen alone," she says. Before the estrogen-progestin arm was stopped last summer, the study investigators had sent out two letters warning participating doctors that there appeared to be excess risk associated with the combination therapy. Asked if similar warning letters have been sent to doctors supervising the estrogen-only arm, Smoller says no such warnings have been sent.


While Smoller was unflinching in her assessment of the risks associated with the combination regimen, adding that use of those hormones can be linked to "4,800 excess strokes each year," Lawrence Brass, MD, professor of neurology at Yale University School of Medicine, New Haven, Connecticut is not so sure. He tells WebMD that the latest word from the Women's Health Initiative researchers is "not the final word on hormones and stroke."

Brass, who was not involved in Smoller's study, says "what is clear is that estrogen has an effect on the system, so we were right about that. It's just not the right effect. It turned the knob the wrong way but it may still be possible to find a way to turn the knob the right way."

He says, for example, that estrogen may actually be beneficial if some other drug -- like aspirin or other blood thinner to prevent blood clots -- is given in combination with the hormone. Or, he says that drugs like Evista, which is a selective estrogen receptor modulator, may provide the protective benefit that Smoller and other researchers have not found with estrogen.

Source: American Stroke Association 28th International Stroke Conference.

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