RT Journal A1 Petitti DB T1 Hormone replacement therapy and heart disease prevention: Experimentation trumps observation JF JAMA JO JAMA YR 1998 FD August 19 VO 280 IS 7 SP 650 OP 652 DO 10.1001/jama.280.7.650 UL http://dx.doi.org/10.1001/jama.280.7.650 AB Three different meta-analyses1- 3 have concluded that estrogen replacement therapy (ERT) decreases the risk of coronary heart disease (CHD) by 35% to 50%. The predicted increase in life expectancy in hormone users, based on estimates of the risk of CHD in users of ERT derived from observational studies, is 2 to 3 years.2,4 The effects of ERT and combined estrogen-progestin replacement therapy (HRT) on lipids and fibrinolysis are strongly beneficial for both ERT and HRT.5 This has led to extrapolation of the results of observational studies of ERT to HRT and to promotion of the use of both ERT and HRT in women with CHD.2,6 The results of the Heart and Estrogen/progestin Replacement Study (HERS), which are reported by Hulley et al in this issue of JAMA,7 add critically important data on the effects of HRT. In this randomized controlled trial of 2763 postmenopausal women with established coronary disease, treatment with estrogen plus progestin did not reduce the rate of CHD events (eg, nonfatal myocardial infarction or CHD-related death). These findings are a sobering reminder of the limitations of observational research, the incompleteness of current understanding of the mechanisms of vascular disease, and the dangers of extrapolation.