By Rob Stein
Washington Post Staff Writer
Tuesday, February 14, 2006
Estrogen does not increase the risk of heart disease for women in their fifties and may even be protective, according to a new analysis that reassures women it is safe to use the hormone for short-term relief of hot flashes and other symptoms of menopause.
The first analysis of data focusing specifically on younger women in a landmark government study found no increase in heart disease among those age 50 to 59 taking estrogen, and some hints that the hormone may reduce their risk of the most common killer.
The findings are the latest development in a long, often confusing history of hormone use during and after menopause. Millions of women stopped taking estrogen after earlier research concluded it was dangerous. The new findings should ease their concerns about heart disease, experts said.
"These findings are reassuring for women who want to use these hormones around the age of menopause in the short term for the relief of symptoms," said Jacques Rossouw of the National Heart, Lung and Blood Institute, which funded the research published yesterday in the Archives of Internal Medicine. But experts, including some of the researchers involved in the new analysis, disagreed sharply about whether the findings also support a controversial theory that the hormone may prove to be effective for cutting a younger woman's risk of heart disease.
"We're not suggesting at this point that women use estrogen for the express purpose of preventing cardiovascular disease," said JoAnn E. Manson of Brigham and Women's Hospital in Boston. "But this does suggest that more research is needed on younger women and recently menopausal women to explore this question. There may be a window of opportunity when women will have some heart protection from estrogen."
Others, however, said the findings were so weak that no one should interpret them to support the idea that estrogen protects against heart disease.
"That's really a deceptive message," said Marcia L. Stefanick of Stanford University, noting that the hormone may increase the risk for other health problems, including strokes and blood clots. "It confuses the public, and at this point it is just not helpful to add confusion. We tested that hypothesis and showed very clearly that one should not take hormones to prevent cardiovascular disease. Some people just don't want to accept that."
For years, millions of women used estrogen alone or in combination with progesterone on the advice of doctors who believed it would alleviate hot flashes, memory problems and other symptoms; protect their bones; and reduce the risk of heart disease.
The Women's Health Initiative, a large federally funded study, stunned women and the medical establishment in 2002 when it concluded that estrogen combined with progesterone not only did not reduce the risk of heart disease but also appeared to increase the chance of suffering heart attacks, strokes, blood clots and breast cancer. Use of the hormones plummeted.
Some researchers questioned the findings, however, saying they may not apply to younger women because most of the subjects in the study were in their sixties and seventies, when they may have been too old to benefit from estrogen.
The new findings address the main concern about estrogen's safety -- heart disease -- and stem from one part of the initiative that evaluated 10,739 women, age 50 to 79, who had undergone hysterectomies and took estrogen alone. (Women with an intact uterus are not given estrogen alone because it increases the risk of uterine cancer.) The initial results of that study, released in 2004, found no evidence that estrogen either increased or decreased the risk of heart disease.
As part of the study's final analysis, researchers examined data collected from 3,310 women who were 50 to 59 when the study began. About half took estrogen, and the other half took a placebo.
After about seven years, the younger women on estrogen were no more likely to have a heart attack or die of heart disease than those on the placebo. In fact, they were about 37 percent less likely to have a heart attack, although that finding could have been the result of chance. But when the researchers added together women who died of heart disease, had heart attacks, and were treated for or had symptoms of cardiovascular disease, they found a 34 percent lower risk in the estrogen-taking group. That difference did pass a statistical threshold, making it unlikely to be due to chance. Forty-six women taking hormones suffered one of those events, compared with 70 of those taking placebo.
That finding was seized upon by proponents of the "window of opportunity" hypothesis that estrogen may be protective if women take it before their arteries start to become diseased.
"All of this points to the idea that if you start estrogen early, you might protect women," said S. Mitchell Harman of the Kronos Longevity Research Institute in Phoenix, which is sponsoring one of two studies on that question. "Timing may be important."
But skeptics remained unconvinced, saying the number of women in the new study and the type of analysis make the findings highly questionable.
"I'm underwhelmed," said Deborah Grady of the University of California at San Francisco. "You really have to be careful when you take data from a trial and start slicing it up based on certain characteristics to try to prove the drug works differently in one group than another."
Both sides agreed, however, that at the very least women in their fifties should be reassured that they can safely use hormones for short periods to relieve symptoms without fear that they will endanger their hearts.
"The pendulum has swung back. We went from the early '90s, when you thought estrogen was a panacea to be given to everybody, to when it was almost thought estrogen ought to be outlawed," said Isaac Schiff of Massachusetts General Hospital in Boston. "For a woman in her fifties whose life has become miserable because she's having hot flashes 25 times a day and other symptoms, this is very reassuring."