The older a postmenopausal woman is, the more likely hormone therapy will increase her risk of heart disease, especially if she is still having hot flashes, according to a new analysis of data from a landmark government study.

The Women’s Health Initiative in 2002 reported that Prempro, a combination of estrogen and progestin, raised postmenopausal women’s risk for heart attack, stroke, blood clots and breast cancer after four years of treatment on average. Less than two years later, a parallel study found that estrogen alone raised the risk of stroke, but not of heart attacks or breast cancer after five years of treatment on average.

Numerous previous studies comparing women who chose on their own to go on hormone therapy found that it protected the heart. Skeptics speculated that the government trial, which randomly assigned volunteers to hormone therapy or a placebo, focused on women who were too old to benefit from estrogen.

“All of our investigators give many talks, and that issue kept recurring,” says Jacques Rossouw of the National Heart, Lung, and Blood Institute and lead author of the new analysis, out Wednesday in The Journal of the American Medical Association. “We said, ‘hey, you know, although this wasn’t our original purpose and design, we still have the best data on this.’ ”

The new analysis pools data from both the estrogen-only and estrogen-plus-progestin components of the trial. On average, U.S. women go through menopause at 51; the average age of women in Roussouw’s trials was nearly 63.

Among participants who had started menopause less than 10 years before enrolling in the study, those on hormones had a lower risk overall of dying and of coronary heart disease than those on placebo, the new analysis found. But there were so few deaths and heart attacks in that group that the difference was not statistically significant, the researchers write. In other words, it could have been due to chance.

By age, the biggest difference in heart disease risk and overall deaths between hormone therapy and placebo was in women 70 to 79. The difference was greatest among women 60 or older and still having hot flashes, who tended to have more risk factors for heart disease, Rossouw says. Breast cancer and stroke risk were not linked to age.

The finding that hormone therapy did not raise the risk of heart disease or death in women 50-59 “offers some reassurance that hormones remain a reasonable option for the short-term treatment of menopausal symptoms,” but extended use could still be harmful, the researchers write. And estrogen plus progestin still raised stroke risk in women 50 to 59, they note.

“Do hormones prevent coronary artery disease?” Rossouw says. “The answer was ‘no’ then (when the data from the estrogen and estrogen-plus-progestin trials were originally reported) and ‘no’ now.”

Perhaps estrogen protects against early coronary artery disease, he says, but eventually, as it advances, estrogen will increase heart attack risk. “At what point does this switch occur? No one knows, and we’ll never know,” Rossouw says, citing the need for a prohibitively expensive trial.

Mitchell Harmon, director of the Kronos Longevity Research Institute in Phoenix, says Rossouw might have found a significant heart benefit had he focused on women in their early 50s.

“Fifty-nine is already too old,” says Harmon, who is enrolling 720 women no more than three years past menopause in a hormone therapy trial.

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