The Time Has Come to Stop Letting the HERS Tale Wag the Dogma

The premise of this commentary is simple. We believe there has been enormous overinterpretation and misinterpretation of recent clinical data (the HERS tale1) with regard to the efficacy of hormone replacement therapy (HRT) in preventing or diminishing the risk of heart disease (the dogma). Both the medical and lay press have focused on obtaining a single yes-or-no answer to the question, “Does postmenopausal HRT reduce the risk of cardiovascular disease (CVD)?” This oversimplified approach has led to unjustified generalizations with regard to the question and to the summary judgment in some circles that HRT is not beneficial for the prevention of heart disease.See p 2300 A brief review of the literature in this area reveals the source of much of the controversy and confusion. In 1992, an elegant meta-analysis by Grady and colleagues2 concluded that “there is extensive and consistent observational evidence that estrogen use reduces risks for CHD [coronary heart disease] about 35%.” This conclusion has since been supported by additional observational studies that together include several hundred thousand woman-years of follow-up. As one example, a recent update from the Nurse’s Health Study (>400 000 woman-years of follow-up) again confirmed a 40% to 60% reduction in cardiovascular events in women taking HRT.3,4 In contrast to this large body of observational data, the recent prospective Heart Estrogen/progestin Replacement Study (HERS) proved negative. HERS, the first prospective, randomized trial of HRT assessing cardiovascular end points, demonstrated that combined HRT (0.625 mg/d conjugated equine estrogens [CEE] and 2.5 mg/d of medroxyprogesterone acetate [MPA]) had no effect on fatal or nonfatal cardiac events.1 The study included 2763 women with established coronary artery disease followed up for an average of 4.1 years. It is largely the discrepancy between the results of HERS and the many prior observational studies that …