Five years after a landmark study scared millions of women off hormones for menopause symptoms, new research suggests the pills may offer some heart benefits for certain younger women who start taking them in their 50s.
Women who took estrogen suffered less hardening of the arteries than those who took dummy pills, researchers reported in Thursday's New England Journal of Medicine.
It was the latest study in recent months to suggest that women who take hormones at the start of menopause seem to gain some health benefits beyond relief from hot flashes. That is in sharp contrast to women who raise their health risks when they start hormones in their 60s and 70s.
In general, experts' advice hasn't changed: Take hormones to treat hot flashes, sleeplessness and other symptoms at the start of menopause. And take them no longer than four or five years.
The new study is the latest attempt to sort out how menopause hormones affect the risk of cancer, Alzheimer's disease, stroke and heart problems, and whether those risks and benefits differ by age.
The research concludes that women who started taking estrogen pills in their 50s were 30 to 40 percent less likely to have measurable levels of blockage-causing calcium in the arteries that lead to the heart.
"It seems to be slowing the rate of plaque buildup," said Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women's Hospital. She is the study's lead author.
The research is based on the Women's Health Initiative, a huge federal study started in the 1990s that focused on the risks and benefits of menopause hormones for women.
One phase of the study was suspended in 2002 after researchers detected higher rates of heart attacks, strokes, breast cancer and other problems in women who took an estrogen-progestin combination pill. Many women were startled by the findings; millions stopped taking hormones.
"The heart attack issue was really the thing that surprised us all," said Dr. Michelle Warren, a Columbia University expert who is a consultant for Wyeth Pharmaceuticals, which makes which makes top-selling hormone pills Prempro and Premarin.
Another phase of the big women's study was stopped in 2004 when researchers saw higher risks for strokes and blood clots in women who took estrogen alone. (Levels of heart disease and breast cancer were unaffected by the solo pill.)
Since then, some scientists have begun to slice the large study's data for more nuanced meaning. They note that most of the women in the study were in their 60s or 70s, several years post-menopausal when the research began. New analyses are focusing on women who were in their 50s when they joined the study.
The scientists are researching a "timing hypothesis" that proposes that estrogen can help against clogged arteries and heart disease, but only when given before problems develop and before natural estrogen levels have been low for an extended period of time. Estrogen can trigger heart attacks in women who have advanced atherosclerosis, experts said.
Warren likened it to exercise: When started earlier in life and done regularly, it can protect a heart. "But if I take a woman who's 63 years old, who's never exercised, and start her on it, I can kill her," she said.
In the new research, Manson and her colleagues focused on more than 1,000 women in their 50s who had hysterectomies. Roughly a quarter of U.S. women in that age bracket have had a hysterectomy, Manson said.
The women were either on estrogen or dummy pills for an average of about 7 1/2 years. They then had cardiac scans in 2005 to check for buildup of calcium in the arteries. The women were 64 years old, on average, at the time of the scans. There was no baseline scan of the women when the study started.
One expert who consults for Wyeth, Dr. Howard Hodis of the University of Southern California, celebrated the results as evidence that estrogen — started at the right time — could be taken for decades.
Other experts said that is going too far.
"Wishful thinking," said Dr. Jacques Rossouw, a federal researcher who oversees the Women's Health Initiative.
Risks for stroke and blood clots remain with continued hormone use, noted Dr. Nanette Wenger, an Emory University expert on heart disease in women. Still, the latest findings should provide some comfort to menopausal women who are considering taking estrogen, she said. "This is quite an important study."
The risk of serious heart problems for women in their 50s is low. An earlier study by Manson and others estimated that for women in that age group, 27 in 10,000 women would suffer a heart attack in a year, and 17 in 10,000 would have a stroke.
For women on estrogen, the estimates were 17 and 15, respectively, per 10,000.
Hardening of the arteries is considered a strong predictor of heart attacks, but heart attack reduction is the real goal. So far, for younger women, there is no conclusive medical evidence about the impact on heart attacks.
Women who want to prevent heart disease should focus instead on healthy eating, exercise and not smoking, Wenger said.
Manson agreed. "Estrogen is known to have other risks and should be used only for the treatment of menopausal symptoms at the lowest dose for the shortest duration necessary," she said.