MONDAY, April 28 (HealthDay News) -- No matter when postmenopausal women start hormone replacement therapy (HRT), high doses of the treatment increase their risk of stroke, a new study finds.

The risk for stroke does appear lower in younger women taking HRT and in those taking the lowest doses of estrogen, Harvard researchers say. However, in women who took high doses of hormones, that increased risk was as much as 62 percent.

"If you take medium to higher doses of hormone therapy, you are at increased risk of stroke," said Dr. James Liu, chairman of the Department of Obstetrics and Gynecology at MacDonald Women's Hospital, University Hospitals Case Medical Center in Cleveland.

"If you are on estrogen, the risks of clotting abnormalities are slightly increased versus if you are not on estrogen," Liu said. "So, the risk of stroke is increased."

The report was published in the April 28 edition of the Archives of Internal Medicine.

In the study, Francine Grodstein and colleagues at Brigham and Women's Hospital and Harvard Medical School collected data on 121,700 women who participated in the Nurses' Health Study from 1976 to 2004.

The researchers looked at the association between HRT and stroke. Over the course of the study, 360 women who had never used HRT had strokes compared with 414 women taking hormones, Grodstein's team found.

"This increased risk was observed for women initiating hormone therapy at young ages or near menopause and at older ages or more than 10 years after menopause," the researchers wrote.

However, women taking HRT for less than five years at younger ages did not have a clear increase of stroke, which might be due to the small number of cases studied, the researchers noted.

"The incidence of stroke was relatively low in younger women, and the attributable risk in women aged 50 through 54 years indicated approximately an additional two cases of stroke per 10,000 women per year taking hormones," the researchers added.

Liu noted that older women are at an increased risk of stroke due to their age, whether or not they are taking HRT.

In addition, higher doses of estrogen were associated with an increased risk for stroke, Grodstein's group found. In fact, women taking high doses of estrogen increased their risk of stroke by 62 percent.

"In summary, our findings in the Nurses' Health Study indicate that hormone therapy is associated with an increased risk of stroke, regardless of the hormone regime or the timing of hormone therapy initiation," the researchers concluded. "However, in younger women, who are at lower absolute risk of stroke, the attributable risk of stroke owing to hormone use is modest, and our data suggest that risk might be further minimized by lower doses and shorter duration of treatment."

Liu noted that HRT is given differently than it was in 1976. "The doses we're using now are much, much lower," he said.

"The advice to women is, if you are on HRT, you should be on the lowest dose that will control your symptoms," Liu said. "In addition, you should be monitored and evaluated, and if you are going to continue on it; you need to understand what the risks are."

Another expert thinks only women with the most severe symptoms should start HRT, and then only at the lowest dose.

"You don't really see an increased risk of stroke with the lowest estrogen does," said Dr. Jennifer Wu, an obstetrician/gynecologist at Lenox Hill Hospital in New York City. "This study confirms that you should be on hormone replacement therapy for the shortest time possible at the lowest dose."

Wu thinks only women with the most severe menopausal symptoms who can't function well on a daily basis should start HRT. "We try to start [on] the lowest dose possible and decrease that dose even further, if possible," she said. "We keep them on a low dose for six months, and then take them off and see how they do."

Wyeth Pharmaceuticals, which sells the hormone therapy called Premarin, said in a statement that the findings reflect previous research and the current labeling on all hormone therapy products.

"Hormone therapy continues to be an effective option for many women when used at the lowest dose for the appropriate duration consistent with treatment goals and risk for the individual woman," Danielle Halstrom, senior director of global public relations at Wyeth Women's Health Care, said in a statement. "Hormone therapy is the most effective FDA-approved treatment for menopausal symptoms, and the benefits of hormone therapy may outweigh the risks for many symptomatic menopausal women."

More information

For more on hormone replacement therapy, visit the Women's Health Initiative.

SOURCES: Jennifer Wu, M.D., obstetrician/gynecologist, Lenox Hill Hospital, New York City; James Liu, M.D., chairman, Department of Obstetrics and Gynecology, MacDonald Women's Hospital, University Hospitals Case Medical Center, Cleveland; April 28, 2008, statement, Danielle Halstrom, senior director, global public relations, Wyeth Women's Health Care; April 28, 2008, Archives of Internal Medicine

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