Hormone Replacement Therapy (HRT) Trial Halted< July 23, 2002 > Researchers have pulled the plug on one part of a massive review of health risks to post-menopausal women. The national study was examining the effects of hormone replacement therapy (HRT), using a combination of estrogen and progestin, but it was cut short after the health risks were found to outweigh the benefits. The trial was cancelled after 5.2 years of average follow-up, or more than three years before its expected duration of 8.5 years. An article in the July 17 issue of the Journal of the American Medical Association (JAMA) reports that women taking the common combination hormone therapy experienced a 29 percent increased rate of coronary heart disease problems, compared to women taking a placebo. In addition, stroke rates were 41 percent higher in women receiving both hormones; the rates of blood clots doubled; invasive breast cancer rates were 26 percent higher; and total cardiovascular disease increased by 22 percent. On the plus side, the women taking the estrogen and progestin experienced a 37 percent drop in colorectal cancer rates; hip fracture rates declined by one-third; and total fractures decreased by 24 percent. Dr. Philip Sarrel, a professor emeritus of obstetrics, gynecology, and psychiatry at Yale University School of Medicine, says the study's results may be traced to the type of progestin (medroxyprogesterone acetate) that was used. Basically, the type of progestin used counteracted the beneficial effects of estrogen, Sarrel says. "What we know from the basic research and many, many other trials is that the effects of estrogen are protective, but their mechanism of action depends on estrogen receptors. And the drug that was used in the trial that was stopped is a combination of estrogen with a progestin which is a very potent down regulator of the estrogen receptor," Sarrel adds. The study was part of a broader review known as the Women's Health Initiative (WHI). "We have long sought the answer to the question: Does post-menopausal hormone therapy prevent heart disease and, if it does, what are the risks? The bottom-line answer from WHI is that this combined form of hormone therapy is unlikely to benefit the heart," Dr. Claude Lenfant, director of the National Heart, Lung, and Blood Institute, says in a prepared statement. "The cardiovascular and cancer risks of estrogen plus progestin outweigh any benefits—and a 26 percent increase in breast cancer risk is too high a price to pay, even if there were a heart benefit," Lenfant adds. "Similarly, the risks outweigh the benefits of fewer hip fractures." The WHI is a large ongoing clinical trial sponsored by the National Institutes for Health (NIH) that is designed to look at the major causes of death and disability in post-menopausal women. The overall goal is to reduce coronary heart disease, breast and colorectal cancer, as well as fractures caused by osteoporosis in women in this age group. The cancelled portion of the trial was looking at the risks and benefits involved in using the most commonly prescribed hormone preparation in this country. Seven million women currently use this combination daily. According to the authors of an editorial in the same issue of the Journal of the American Medical Association, some 38 percent of post-menopausal women in the United States use HRT. The US Food and Drug Administration (FDA) has approved HRT for relief of menopausal symptoms and prevention of osteoporosis, but many women use it to stave off other infirmities of old age. The trial—the first randomized, controlled study of combination hormone therapy—recruited 16,608 healthy women between the ages of 50 and 79. Formal monitoring began in 1997 and, by late 1999, the trial's Data and Safety Monitoring Board noticed some of the women were having cardiovascular problems, though not enough to cancel the review. In the spring of 2000 and 2001, the board saw more indications of increased heart attacks, strokes, and blood clots, but still felt the overall picture was unclear. In May 2002, when it was clear the dangerous cardiovascular effects were persisting, the study was stopped. The authors of the JAMA article emphasize the numbers are still low: Over the course of one year, 10,000 women taking estrogen and progestin might experience seven more "cardiovascular events," eight more strokes, eight more invasive breast cancers, six fewer colorectal cancers and five fewer hip fractures than women not taking the hormones. However, when multiplied by the millions of women who use combination estrogen with progestin, the harm could be significant, the authors say. The other portion of the hormone replacement trial, which is assessing the effects of estrogen alone, is continuing. In the meantime, officials are urging women to look to other, proven methods for preventing various health problems. "Menopausal women who might have been candidates for estrogen plus progestin should now focus on well-proven treatments to reduce the risk of cardiovascular disease, including measures to prevent and control high blood pressure, high blood cholesterol, and obesity," Lenfant says. "This effort could not be more important; heart disease remains the number one killer of American women." Always consult your physician for more information. Online Resources:(Our Organization is not responsible for the content of Internet sites.) Journal of the American Medical Association (JAMA) National Heart, Lung, and Blood Institute |
For more information, please visit the Women's Health Information Module of this Web site. In Other News About Hormone Replacement Therapy:HRT No Savior for Women With Heart ProblemsEstrogen replacement therapy does not prevent recurrent heart attacks and cardiovascular deaths in women with a history of heart disease. That is the result of a new study that adds the much-needed perspective of time to an earlier report that reached the same conclusion. "At least for older women with heart disease, we don't see any benefit for the use of estrogen plus progestin," says Dr. Stephen Hulley, an epidemiologist at the University of California, San Francisco, and a co-author of two papers on the new research. "Things might be different for women who are healthy, and who take [hormone therapy] during menopause." When results from the widely awaited HERS study arrived in 1998, physicians were surprised to learn the combination of estrogen and a progestin did not prevent more heart attacks, strokes, and other cardiac problems in older women with a history of such trouble. In fact, the study showed that for these women, the risk of heart complications increased during the first year or so of hormone replacement therapy (HRT) before dropping off in subsequent years. At the time, experts advised post-menopausal women with heart trouble not to start HRT if they wanted to prevent additional problems, and suggested other treatments instead. However, since the roughly four-year-long HERS study also hinted that HRT might protect the heart in the long run, they told women already taking the hormones to prevent cardiac illness to be patient and await further study results. The new study, called HERS II, found HRT offered no long-term heart protection, compared to placebo treatments, in more than 2,300 women from the original trial who agreed to stay in the project for nearly three more years. What's more, they had a 50 percent higher risk of needing gall bladder surgery and were twice as likely to develop potentially dangerous blood clots in their legs and lungs than those not on hormones. The risk of clotting fell as the study progressed, but the odds of requiring gall bladder surgery rose, says the study, which appeared in an early-July issue of the Journal of the American Medical Association (JAMA). Dr. Lori Mosca, author of the American Heart Association's 2001 guidelines reflecting the first HERS study, says the latest findings support the recommendation that women with heart disease not use HRT to prevent additional cardiac problems. However, she acknowledges that for those with heart disease already on the drugs, what to do now might be confusing. "The answer lies with what they're taking [HRT] for," says Mosca, director of preventative cardiology at New York-Presbyterian Hospital in New York City. "For women who have heart disease that are on HRT for established benefits such as menopausal symptoms or preventing thinning of the bones, there is no reason to discontinue it," she says. "However, if a woman with heart disease is on HRT for the purpose of preventing further heart disease, then she should consider other therapies that are known to prevent recurrent" heart attacks and strokes. These include statin drugs to lower cholesterol, aspirin, blood pressure medications, beta blockers, and ACE inhibitors. Experts say this time, they were not caught off guard by the findings. "We need to stop thinking of hormone replacement therapy as one-stop shopping for women's health," says Dr. Nieca Goldberg, a cardiologist at Lenox Hill Hospital in New York City and author of Women Are Not Small Men. "It's beneficial in menopausal symptoms and osteoporosis prevention, but the data supporting it for reducing [heart disease] are still not here," Goldberg says. The ongoing Women's Health Initiative is looking at whether HRT can prevent heart attacks and other cardiovascular trouble in 27,000 women, fewer than 10 percent of whom had a history of such problems when the study began. Neither the initial HERS study nor its follow-up addresses that question, Goldberg says. HRT does lead to somewhat lower "bad" cholesterol and higher "good" cholesterol levels. Some researchers had expected these changes to result in less heart and vessel disease. However, Dr. Jacques Rossouw, of the National Institutes of Health (NIH), says "it's starting to look very much like these apparently beneficial effects on blood [fats] are irrelevant." Rossouw, who is directing the Women's Health Initiative for the National Heart, Lung, and Blood Institute, says women should still consider HRT to control symptoms of menopause like hot flashes, insomnia, and vaginal dryness. For now, the message to those with cardiovascular disease should be: "Don't start to prevent it and don't continue" if you are on it, he says. The study was supported by Wyeth-Ayerst, maker of Premarin, the leading formulation of estrogen and the nation's most widely prescribed drug. Always consult your physician for more information. |