Once Promising, Future of HRT Dwindles
Only Use for Combination Therapy Appears to Be Menopause Symptoms
Oct. 23, 2002 -- In July, the National Institutes of Health announced it was ending one part of a hormone-replacement therapy trial due to increased risk of breast cancer and, surprisingly, heart disease. The announcement overturned long-held assumptions that HRT has preventive benefits against heart disease.
The results show that "no woman will benefit from preventive [estrogen and progestin combination] therapy," said Deborah Grady, MD, MPH, of the University of California at San Francisco, in front of a large audience of doctors at a meeting at the National Institutes of Health today. A related trial, evaluating the use of only estrogen in women who have had hysterectomies, has shown no clear sign of harm to women and will continue. Women with an intact uterus cannot take estrogen alone because it can cause uterine cancer.
The trial's disappointing outcome does not, however, count out the use of combination therapy for the symptoms of menopause, which can cause severe hot flashes and other problems in many women. The increased risk shown by the study is small for an individual. For every 10,000 women, the trial showed that 38 women would likely get breast cancer if they were on combination therapy, compared with 30 cases of women who did not receive the treatment. There was a similar heightened risk of strokes and blood clots, but the treatment showed some counterbalancing benefits, including a reduced risk of hip fractures and colorectal cancer.
Overall, the study showed that the risks slightly outweighed the benefits, meaning that women taking the HRT were actually slightly more likely to have something bad happen to them over the course of treatment. If 1,000 women take the drugs for a year, an average of two more negative effects would occur among all of the women.
"It's not that big a risk, but it's certainly not the benefit we were looking for," said Marcia L. Stefnick, PhD, of Stanford University, who is one of the researchers who worked on the trial.
Several doctors on the panel stressed that the increased risk is quite small on a personal level but the societal risk is much higher. With some estimates putting the number of women on combination therapy at 10 million, two bad events per 1,000 women per year translates to 20,000 cases of breast cancer, blood clots, heart disease, or some other ill effect, and it is that figure that prompted the NIH to halt the trial and reconsider the use of combination HRT.
Still, the hormones are clearly the best option for treating the symptoms of menopause, leaving many women confused about what to do. The trick, say doctors, is to weigh the severity of symptoms against the risk.
Another key consideration of the study: it measured long-term effects. Because menopausal symptoms are often short-term, with most symptoms tailing off after two to five years, women may only need to use the drugs for a short period of time. Doctors called for short-term studies to assess those risks and benefits, as well as studies to determine which women are likely at heightened risk. "We need to determine which women are at a high-enough risk that they should avoid hormone therapy even if they have [difficult] symptoms," said Grady.
"Now we need to ask, why should you take hormones? The question is, how severe are the symptoms that can only be treated by hormones?" said Marian C. Limacher, MD, of the University of Florida College of Medicine.
More specifically, how do those symptoms balance against the increased risk?
Only a woman and her doctor can provide that answer. -->