25,000 women taking part in a federal study of hormone replacement therapy have been informed by researchers that, far from protecting the heart as many researchers had assumed, the therapy may have put the women at a slightly higher risk of heart attacks and strokes.

The study, known as the Hormone Replacement Therapy trial of the Women's Health Initiative, is the first large-scale controlled clinical trial asking whether the therapy prevents heart disease in healthy post-menopausal women.

But in letters sent out on Friday, participants were told that those who had been randomly assigned to take estrogen were having slightly more heart attacks, strokes and blood clots in the lungs than those who had been assigned to take dummy pills for comparison. While the effect was not sufficiently pronounced to stop the study, the researchers themselves were taken aback.

An estimated 10 million American women take Premarin, an estrogen that was approved only to alleviate the symptoms of menopause, like hot flashes, and for the prevention and management of osteoporosis.

The drug's maker, Wyeth-Ayerst Laboratories, a subsidiary of the American Home Products Corporation, says the estrogen is the best-selling prescription drug in America.

Doctors and individual women say that one reason for estrogen's popularity is that there is a widespread belief that it will prevent heart disease. But that hypothesis came from indirect evidence.

Dr. Claude Lenfant, director of the National Heart, Lung and Blood Institute, said in a statement on Monday that the new information is "preliminary." It does not address the larger issue of long-term benefits and risks of hormone replacement therapy, he said, "and, therefore, it should not influence current medical practice."

Previous studies have shown that women who take estrogen after menopause have fewer heart attacks than women who do not.

But since women who take the hormone tend to be better educated, less likely to smoke and more likely to eat balanced diets and exercise, it was hard for researchers to tell whether the therapy or other factors in their lives contributed to their lower risk. The only way to know for sure was to do a large study like the current one.

Dr. Jacques E. Rossouw, who is acting director of the hormone replacement trial, said in an interview yesterday that even though it was too soon to say whether the increased risk of heart attacks and strokes would hold up as the study continued, he felt morally obliged to inform the women about the finding.

"This wasn't anticipated when they enrolled," Dr. Rossouw said. "We told them all about the risks and benefits but we didn't tell them there might be an increased risk of heart disease."

He added that he fervently hoped that the women would stay in the study and that other women would not panic because the number of women who had had heart attacks and strokes was minuscule.

"If my women friends ask me, 'How does this affect me?', my advice is it doesn't change a thing," Dr. Rossouw said. "I would say there never was proof that hormones help heart disease and there still isn't. The only qualifier is, if you're expecting an early benefit from heart disease it looks less likely."

Investigators emphasize that only a small number of women in the study actually had heart attacks, strokes or blood clots in the lungs or the legs. The exact numbers were in the hands of an independent committee that oversees the study, and its members would not reveal them even to the study investigators. But overall, only about 1 percent of all the women, who were 50 to 79, had these problems in the first two years of the study. The effect seems to be diminishing as the study continues, the researchers say. Yet apparently, these grave medical problems were disproportionately concentrated in the women taking hormones that were supposed to prevent them.

"This is the most widely prescribed drug in America," said Cindy Pearson, the executive director of the National Women's Health Network, an advocacy group in Washington. "A lot of the women are taking it because they've been told by their doctors that it will prevent a heart attack. Those are the women who should be sitting up and taking notice and going to their doctors and saying, 'Why am I taking this? What's the point of this?' "

Ms. Pearson said that in her opinion no woman should be taking estrogen to prevent heart disease outside of a clinical trial asking if it has that effect.

Some heart disease researchers said that they already were wary about estrogen because it can elicit blood clots, which can cause heart attacks and strokes. Birth control pills, which contain estrogen, may cause clots, and a recent study found that women who already had heart attacks might not be protected from new ones if they take estrogen.

The study, directed by Dr. Stephen Hulley of the University of California at San Francisco, found that in the first year, women taking estrogen actually had more heart attacks and other manifestations of heart disease than those taking a placebo. The effect diminished in subsequent years, and by the fifth year the women taking estrogen did better than those taking the placebo. But the study failed to show that overall, women who had had heart attacks were helped by estrogen.

Another study, decades ago, in which men took estrogen in the hope of preventing heart attacks, had to be discontinued because the hormone was causing heart attacks instead.

Those who hoped estrogen might benefit healthy women pointed to the studies showing that women who happened to take estrogen had fewer heart attacks than those who happened not to take it. They also noted that estrogen increased the amount of beneficial cholesterol in the blood, the HDL fraction, while decreasing the fraction of the harmful LDL cholesterol. But, Dr. Hulley noted, his study of women who had had heart attacks indicated that those changes could be misleading.

Yet, investigators said, the Women's Health Initiative remains scientists' best hope of learning whether estrogen replacement therapy is helpful or harmful to healthy women.

"No one else is going to do a study this big on hormone replacement therapy," said Dr. Marcia Stefanick, a Stanford University professor who is chairwoman of the study's steering committee. "If we don't answer the questions on hormones, they're never going to be answered."

In the letters they received, participants in the Women's Health Initiative were urged to stay in the study. The study, they were told, "is more important than ever." So far, said Dr. Rossouw, the women are reacting calmly.

In the meantime, said Dr. Michael Criqui, an investigator in the study who is a professor of family and preventive medicine at the University of California at San Diego, "one cannot recommend to a woman to take estrogen to prevent heart disease at this time." So far, he said, "there's no evidence that it will."