Nearly five years after government scientists told women that estrogen replacement therapy increased their risks of heart attack and stroke, researchers have largely reversed their position, concluding that the drugs are beneficial for many after all.
Continuing analysis of the original data indicates that the researchers raised a false alarm for most women and that, if women begin taking the hormones shortly after menopause, the drugs do not raise the risk of heart disease and might even lower it.
The latest findings, published in today's New England Journal of Medicine, show that taking estrogen for seven years or more after menopause reduces calcification of the arteries -- a key indicator of atherosclerosis -- by as much as 60%. High levels of calcification are generally considered a predictor of increased heart attack risk.
The only group of women at significant risk from the drugs are those who delay taking them for at least 10 years after menopause, experts said.
The findings "provide some additional reassurance for women who have been denying themselves relief" from hot flashes and other symptoms of menopause, said Dr. JoAnn Manson of Brigham and Women's Hospital in Boston, who led both the original and the latest research.
The research is based on the Women's Health Initiative, a vast federal study launched in the 1990s.
Virtually all researchers agree that women should not fear using estrogen replacement therapy to mitigate menopausal symptoms. The debate is over how long they may safely continue to do so.
Dr. Elizabeth G. Nabel, director of the National Heart, Lung and Blood Institute, which sponsored the research, said the new findings "do not alter the current recommendations that when hormone therapy is used for menopausal symptoms, it should only be taken at the smallest dose and for the shortest time possible, and hormone therapy should never be used to prevent heart disease."
Dr. Howard N. Hodis, director of USC's Atherosclerosis Research Unit, countered: "There is absolutely no evidence, none, zero, that if you start a woman on estrogen at menopause and continue until she is 80, the risk goes up as she gets older."
There is an increased risk of breast cancer with age for estrogen when combined with progestin, Hodis said at a news conference Tuesday sponsored by Wyeth Pharmaceuticals, and it is not clear whether the risk outweighs the benefits.
"We will never know when we should stop hormones," said Dr. Michelle Warren of the Columbia University College of Physicians and Surgeons, who spoke at the news conference and urged the shortest use possible. But "if you have been on the hormone since the time of menopause, I am not worried anymore."
Dr. Jacques Rossouw, who heads the heart institute's Women's Health Initiative branch, said it was virtually impossible to conduct a study on long-term hormone use because the risks are so low that the number of women required would be prohibitive.
Long-term use of hormone replacement therapy was popularized in 1966 by Dr. Robert A. Wilson's book "Feminine Forever," which touted the treatment as a panacea for menopausal ills. Subsequent animal and small human studies suggested the hormones could help ward off heart attacks and increase bone density.
By the end of the century, an estimated 40% of menopausal women were taking the drugs.
It came as a shock in 2002 when researchers from the Women's Health Initiative reported that the drugs actually increased risks of heart attack and stroke.
Within a year of the report, the number of new prescriptions for estrogen fell by 68% as both physicians and patients shied away from the drugs.
The new study involved a subset of 1,064 women in the Women's Health Initiative study who were ages 50 to 59 and had undergone surgically induced menopause through a hysterectomy. Half were randomized to receive a Wyeth-produced estrogen called Premarin and half a placebo.
The women were on the drugs for an average of 7 1/2 years. About a year after the study was stopped, physicians used CT scans to measure the buildup of calcium deposits, or atherosclerotic plaque, in their blood vessels.
Overall, they found, women taking estrogen had 42% less calcification of their arteries. Women who had taken at least 80% of their daily doses of the drug had 61% less calcification.
The results were "clear and striking," wrote Dr. Michael E. Mendelsohn and Dr. Richard H. Karas of the Tufts University School of Medicine in an editorial accompanying the study. "Now, some clarity about hormone replacement therapy and heart disease is emerging."
Another analysis by Manson and Rossouw, published in the Journal of the American Medical Assn. in April, found a 30% decrease in the number of deaths from any cause among women receiving estrogen during the course of the research.
They concluded that the use of estrogen by women in their 50s would reduce the number of heart attacks per 10,000 women to 17 from 27, and the number of strokes to 15 from 17.