updated 2/17/2006 4:00:00 PM ET 2006-02-17T21:00:00

Women who have higher natural estrogen levels also may have a higher risk of stroke — a novel finding that suggests a possible new way to prevent this deadly disease, doctors reported Friday.

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More study is needed to confirm these results, but they fit with much of what is already known about hormones, said several experts who were not connected with the new work.

“This is really interesting,” said Dr. JoAnn Manson, a women’s health researcher and chief of preventive medicine at Harvard-affiliated Brigham and Women’s Hospital in Boston.

“These findings would be consistent with the increased risk of stroke seen in the Women’s Health Initiative,” the landmark federal study that prompted many women to stop taking estrogen pills after menopause, she said.

The new research was led by Dr. Jennifer Lee of University of California in San Francisco and presented Friday at an American Stroke Association conference.

It involved 7,290 women who participated in a recent study of raloxifene, a “designer estrogen” that blocks that hormone’s action in some parts of the body, like the breast, while increasing its effects in others, like bones.

The study’s main aim was testing raloxifene for treating the bone-thinning disease osteoporosis, a use for which the drug ultimately won approval. Women with osteoporosis who were at least two years past menopause were randomly assigned to get raloxifene or dummy pills for four years.

Lee then analyzed these women’s levels of estradiol, the most potent form of estrogen that circulates in blood.

Estradiol dramatically drops after menopause, and half of the 2,447 women given the dummy pills had no detectable levels of it. Among the rest, those with lower estradiol levels had a 70 percent lower risk of stroke than those with higher levels, she found.

“To see this effect in such a large population ... is quite striking and is surprising,” Lee said.

Check estradiol levels
Among the 4,843 women given raloxifene, the drug seemed to lower stroke risk in those with the highest levels of estradiol. However, these results were so weak that they could have occurred by chance.

A larger study would have to be done to test this possibility, and in healthy women without osteoporosis, Lee said. If the results reported on Friday held up, it would suggest that for every 78 women given raloxifene, one stroke might be prevented, she said.

The study was paid for by Eli Lilly & Co., makers of raloxifene, sold as Evista. Lee has no financial ties to the company.

Should women with a strong family history of stroke have their estradiol levels checked?

“Yes,” said Dr. Daniel Hanley, a stroke specialist at Johns Hopkins University in Baltimore who had no role in the study. “For a woman to know where she might be in this risk profile cannot hurt,” he said.

Dr. Constantino Iadecola, a neurologist at Weill Medical College of Cornell University in New York, agreed.

Lee’s finding “highlights the complexity of these hormonal systems,” he said. “Most likely it is not just whether estrogen is there or not,” but how much is present and how it affects various parts of the body that determines the risk of stroke, breast cancer and heart disease, he said.

Manson noted that high levels of estrogen are linked to obesity, and obesity is known to raise stroke risk — further evidence that Lee’s study is onto something. Lee’s results took into account the women’s weights as well as their ages and other heart and stroke risk factors.

Researchers are interested in doing a similar analysis now of the federal Women’s Health Initiative study results to see whether it bears out what Lee found, Manson said.

It might be that taking hormones after menopause is especially risky for women who already have high natural estradiol levels, she and others said.

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