Stop Taking Prempro, Doctors Warn

July 9, 2002 -- Women should stop taking a popular form of hormone replacement therapy (HRT), doctors warn. The warning applies to Prempro as well as to other oral, high-dose combinations of estrogen and progestin.

A huge clinical trial of Prempro -- the Women's Health Initiative -- came to a screeching halt on May 31. Plans to continue the trial until 2005 have been scrapped. Five-year data show that Prempro increases a woman's risk of breast cancer, heart disease, and stroke. The trial predicts that one in 100 women will have a bad outcome from long-term Prempro use. These risks are small, but they outweigh the drug's benefits of reduced hip fracture and colon-cancer risk.

The researchers found that the frequency of some of the top killers of women went up even further with the estrogen/progestin combination. Among the women on HRT, the chance of having heart disease went up 29%, breast cancer rose 26%, and strokes increased by 41%. HRT did seem to offer protection against some diseases: colorectal cancer was 37% lower, uterine cancer was 17% lower, and hip fractures -- largely from osteoporosis -- decreased by 34%.

The study results and an accompanying editorial were released early and will appear in the July 17 issue of The Journal of the American Medical Association. The editorial advises doctors to stop prescribing combination estrogen/progestin HRT.

"The whole purpose of healthy women taking long-term estrogen/progestin therapy is to preserve health and prevent disease," write Harvard cancer researchers Suzanne W. Fletcher, MD, and Graham A. Colditz, MD, DrPH. "The results of this study provide strong evidence that the opposite is happening for important aspects of women's health, even if the absolute risk is low. Given these results, we recommend that [doctors] stop prescribing this combination for long-term use."

Robert Bonow, MD, president of the American Heart Association, agrees with this opinion.

"The American Heart Association advises that women do not start or continue combined HRT for the prevention of coronary heart disease," Bonow says in a news release.

Many women take HRT to relieve the symptoms of menopause. Might short-term treatment bypass the risks? The study wasn't designed to answer this question -- but it offers some relevant information. Study co-author Ross Prentice, PhD, is director of the Fred Hutchinson Cancer Research Center's Public Health Sciences Division, Seattle.

"We did see evidence of increased risk of coronary heart disease quite early," Prentice tells WebMD. "If Prempro is used for the relief of menopausal symptoms, the time period should be as short as possible. Or a lower dose may be appropriate for some women."

Another part of the Women's Health Initiative continues. This study looks at the use of oral estrogen alone -- Premarin, the second most commonly prescribed medicine in the U.S. Because estrogen alone increases a woman's risk of uterus cancer, the long-term Premarin study enrolls only women who have had a hysterectomy (removal of the uterus). Prentice says that women in this trial are being sent letters assuring them that, so far, there is no significant evidence of an increased risk of breast cancer with Premarin.

The authors of the study note that the findings may not apply to other HRTs. Low-dose estrogen/progestin combinations may be safer, although further study is needed. Transdermal HRTs use a patch to slowly release hormones into the skin. Most patches contain only estrogen although there is a version that contains both estrogen and progestin. The patches slowly let hormones seep into the bloodstream, bypassing the digestive system and the liver. These may also be safer. This is more like the body's normal way of releasing hormones. Again, more study is needed. -->