17 July 2002. The immediate future of hormone replacement therapy in the treatment or prevention of diseases does not look promising. A large-scale, prospective study of the most common formulation in the United States-estrogen with progestin-has been stopped early because of evidence that the hormone combination does more harm than good.
In the today’s issue of the Journal of the American Medical Association, the investigators of the Women's Health Initiative announce that they have halted the portion of the trial comparing estrogen plus progestin versus placebo in healthy postmenopausal women (n = 16,608). After approximately 5 years of follow-up (of a planned 8.5 years), the statistic for invasive breast cancer in the study group had exceeded the stopping boundary for this adverse effect. In addition, the global index that factors in both negative and positive effects of estrogen had tilted too far toward the negative. Small increases in the risk of breast cancer, coronary heart disease, stroke, and pulmonary embolism outweighed small decreases in the risk of hip fractures and colorectal cancer. The study found that for each 10,000 women in the estrogen/progestin group, there would be 8 more cases of invasive breast cancer a year than in the placebo group, 7 more heart attacks, 8 more strokes, and 8 more lung blood clots. On the other hand, there would be 5 fewer hip fractures and 6 fewer cases of colorectal cancer.
It is unclear what effect the findings will have on ongoing or planned trials of estrogen as a protective intervention for AD. The WHI authors stress that they could not distinguish the relative effects of estrogen versus progestin. They also note that they have not yet analyzed the data in this trial for endpoints such as gall bladder disease, diabetes, quality of life, or cognitive function. Such analyses might affect the equation both for individual women trying to decide whether to use hormone replacement therapy and for investigators conducting or planning hormone trials.-Hakon Heimer
Working Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial. JAMA. 17 Jul 2002;288(3):321-33. Abstract