Nearly five years after government scientists told women that taking estrogen replacement therapy increased their risk of heart attack and stroke, researchers have concluded 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, in fact, might lower it.
The latest piece of evidence, in today's New England Journal of Medicine, shows that taking estrogen for seven years or more after menopause reduces calcification of the arteries - one of the key indicators of atherosclerosis - by as much as 60 percent. High levels of calcification are generally considered a predictor of increased risk for a heart attack.
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 the original study and the one to be published today.
Virtually all researchers agree that women should not hesitate to use hormone replacement therapy, commonly called HRT, to mitigate their symptoms when menopause begins. The debate is over how long they safely can continue to do so.
Dr. Elizabeth G. Nabel, director of the National Heart, Lung and Blood Institute, which sponsored the studies, 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."
But Dr. Howard Hodis, director of the atherosclerosis research unit at the University of Southern California, countered that "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 plus progestin, Hodis said at a news conference Tuesday sponsored by Wyeth Pharmaceuticals, but even there it is not clear that the risk outweighs the benefits.
"We will never know when we should stop hormones," said Dr. Michelle P. Warren of the Columbia University College of Physicians and Surgeons, who spoke at the same news conference and who argued for the shortest use possible. But "if you have been on the hormone since the time of menopause, I am not worried anymore."
The long-term use of hormone replacement therapy was popularized in 1966 after the publication of Feminine Forever by Dr. Robert A. Wilson, who argued that it was a panacea for menopausal ills. A host of animal and small human studies subsequently suggested that the hormones could help ward off heart attacks and increase bone density while alleviating menopausal symptoms.
By the end of the century, an estimated 40 percent of menopausal women were taking the drugs.
It was thus a great surprise in 2002 when researchers from the Women's Health Initiative reported that the drugs could increase the risk of heart attack and stroke, because that finding so contradicted earlier studies. The report was so worrisome that the number of new prescriptions written for estrogen fell by 68 percent within a year 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 percent less calcification of their arteries. Women who had taken at least 80 percent of their daily doses of the drug had 61 percent less calcification.
Thomas H. Maugh II writes for the Los Angeles Times.