TUESDAY, July 9, 2002 (HealthDayNews) -- 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 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 that's 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 U.S. Food and Drug Administration 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."
What To Do
For more information on this and other WHI studies, visit the Women's Health Initiative. To learn more about heart disease and women, try the Centers for Disease Control and Prevention.
