Estrogen Study on Menopausal Women Is Stopped

Scientists Found the Hormone Alone Increased the Risk of Stroke and Did Not Prevent Heart Attacks

The federal government yesterday stopped a study testing the supposed health benefits of prescribing estrogen to menopausal women who have had hysterectomies because it found the hormone increased the risk of stroke and did not prevent heart attacks, as many physicians once believed it would.

The decision follows by nearly two years a similar decision to end a study of estrogen combined with another hormone, progesterone, in menopausal women who still had a uterus. That combination turned out to increase heart attacks, stroke, blood clots and breast cancer, while decreasing colon cancer and bone fractures. Less than a year later, it became clear that hormones also raised the risk of dementia.

This latest decision by the overseers of the landmark Women's Health Initiative study disproves for good the theory that replacing the sex hormones that fall steeply after a woman reaches menopause would yield an overall benefit to her health. It marks the final collapse of a medical and commercial edifice that had been constructed over three decades.

The results of the first part of the study, announced in July 2002, caused an uproar, triggering a steep decline in a therapy that was used by nearly 40 percent of post-menopausal women as recently as 1995.

Today, hormones are prescribed only half as frequently as they were two years ago. They are used mostly for short periods to treat menopause symptoms, and almost never for long periods to prevent chronic disease.

The leadership of the National Institutes of Health, which sponsored the study, decided on Feb. 2 to end it after seven years, about a year ahead of schedule. The scientists concluded that more time would not uncover cardiovascular benefits of estrogen that had so far failed to appear, to date, but would further expose participants to the small increased risk of stroke that had emerged.

The 11,000 women in the study "do not have to feel this is some grand emergency for them," said Barbara Alving, director of the Women's Health Initiative. But she said the message is clear: "Women shouldn't take hormone therapy to prevent heart disease."

Most women who take hormones after menopause must take both estrogen and progesterone because estrogen alone overstimulates the lining of the uterus, raising the risk of cancer of the organ. But women who have had a hysterectomy -- a common procedure that removes the uterus -- can take estrogen alone.

NIH officials did not provide detailed results of the estrogen-alone study yesterday, saying that will appear in medical journals starting in April. But they did note two major differences between the two phases of the study.

The earlier study showed that 10,000 women taking hormone replacement for a year would suffer seven more heart attacks and eight more cases of breast cancer. In the estrogen-alone study, there were no increases in either disease among women randomly assigned to take the hormone, compared with those assigned to take a placebo.

The estrogen-alone study did find an "increased risk of stroke . . . similar to what was found" in the earlier study -- eight more strokes per year per 10,000 women on the hormone, according to a statement released by NIH. However, women taking estrogen only also had fewer hip fractures, but no numbers were released. Data on dementia have not been analyzed.

Although the apparent lack of increase in breast cancer in women taking estrogen was "reassuring," the finding is not enough to remove worries about that possible effect, said Isaac Schiff, chief of obstetrics and gynecology at Massachusetts General Hospital. Many studies have shown a link between estrogen supplements and increased breast cancer risk.