March 3, 2004
Estrogen Study Stopped Early Because of Slight Stroke Risk
large federal study of estrogen therapy in postmenopausal women has been stopped a year ahead of schedule because the hormone increased the risk of stroke and offered no protection against heart disease, the government announced yesterday.
The study included only women taking estrogen alone, not those who take combined hormones. An earlier study, halted abruptly in 2002 after the researchers found an increased risk of breast cancer, involved only women taking the combined hormones estrogen and progestin.
The National Institutes of Health, which sponsored the estrogen study, part of the Women's Health Initiative, said it stopped the study because ``an increased risk of stroke is not acceptable in healthy women in a research study.''
But health officials also noted that the increased risk was small, estimated at about eight extra strokes per year for every 10,000 women taking estrogen. In addition, they said, a related study found that the hormone may also increase the risk of dementia and mild cognitive impairment in older women.
``Women should not feel that this is some grand emergency for them,'' said Dr. Barbara Alving, director of the Women's Health Initiative. Dr. Alving said that although women in the study had been instructed to stop taking their pills, other women who use estrogen should discuss the findings with their doctors to decide whether to continue taking the hormone or quit.
The study also found that estrogen alone did not increase the risk of breast cancer or heart disease, a result that was unexpected and that differed from the findings of earlier studies of combined hormones.
But Dr. Alving and other researchers cautioned that the results of the estrogen study have not been fully analyzed and will not be final until they are published in a medical journal, probably within a month or so.
The Food and Drug Administration said yesterday that it would assess the findings to determine whether the labeling on estrogen and the directions to patients should be changed.
Consumer advocates, drug makers and medical groups representing doctors who prescribe hormones differed sharply in their reactions to the announcement.
Cindy Pearson, the executive director of the National Women's Health Network, a consumer group, said, ``What is important is that all those hopes of the last 30 years, that in one version of a hormone pill or another there existed a fountain of youth, those hopes are dashed.''
Ms. Pearson added: ``I was most struck by the trend toward a possible increase in dementia. To see a risk, apparently from estrogen alone, that's really shocking.''
But the drug company Berlex, based in Montville, N.J., which makes estrogen products, issued a statement on the study's findings that emphasized the bone-protecting effects of estrogen, the fact that it did not increase the risks of breast cancer or heart disease and its proven ability to ease the hot flashes and vaginal discomfort sometimes experienced at menopause.
Dr. James Simon, president of the North American Menopause Society, said, ``I think the findings for women are actually quite reassuring, namely that the major issue which women fear, breast cancer, was not increased on estrogen alone after approximately seven years.''
As recently as five years ago, hormones were widely believed to prolong youth and prevent heart disease and other ills. Many doctors urged women to take the pills at the first sign of menopause and continue them indefinitely.
But study after study has chipped away at the purported benefits of hormone therapy, finding that combined hormones increase the risk of breast cancer, blood clots, heart disease, stroke and dementia, and that those risks outweigh the drugs' benefits in preventing broken bones and colorectal cancer.
In the last few years, the advice to women has changed, and hormone use has dropped sharply, by more than 50 percent since 2002. Hormones are still recommended for women who want relief from hot flashes and other symptoms. But those women are urged to take the lowest dose for the shortest time possible.
As for preventing osteoporosis, hormones are no longer the first choice of therapy, the Food and Drug Administration says. Other drugs, like Fosamax, are preferred, with hormones recommended only for women with a risk of fractures who cannot tolerate the other drugs.
Still, one question that remained was whether some of the harmful effects of hormones might be limited to combination therapy and might be avoided by using estrogen alone.
The estrogen study helps answer that question. It included 11,000 women ages 50 to 79 who were assigned at random to take either estrogen tablets or a placebo and were followed for an average of seven years.
Because estrogen by itself increases the risk of uterine cancer, all the participants in the study had had hysterectomies. Therefore, the findings apply mainly to women who have also had the surgery. About 600,000 hysterectomies are performed each year in this country.
About 3.4 million women in the United States who have had the operation take Premarin, according to Wyeth, the drug's maker.
Dr. Alving said that the increased risk of stroke from estrogen became apparent several years ago and that patients were informed in 2000 and 2001 so they could decide whether or not to remain in the study. Ultimately, about half dropped out.
In 2003, a patient safety board examined the data, and its members were split about whether to stop the study. Health institute officials decided to end it because of the stroke risk and because they believed that another year would not add meaningful data.