Postmenopausal hormone therapy: a reversal of fortune.

How did it become common clinical practice in past decades to prescribe postmenopausal hormones for the prevention of coronary heart disease (CHD)? Postmenopausal hormone therapy (HT), although approved by the US Food and Drug Administration for the treatment of postmenopausal symptoms and the prevention of osteoporosis, was never approved for the prevention of CHD. The recent data from the Women’s Health Initiative (WHI) and other randomized clinical trials (RCTs) indicate that combined estrogen and progestin may increase , rather than decrease, CHD risk.1 This news has alarmed women worldwide and has left physicians uncertain what to recommend to their patients. Recently, the North American Menopause Society released recommendations stating that estrogen and progestin should not be prescribed for primary or secondary prevention of CHD.2 The effect of unopposed estrogen and other formulations of HT on CHD remains unclear; more insight on the former will emerge from the still-ongoing estrogen component of the WHI. The surging popularity of HT use during the past few decades was largely based on findings from observational epidemiologic studies.3,4 Observational studies suggested that HT may reduce the incidence of CHD, fractures, and colorectal cancer but may increase the incidence of endometrial cancer, breast cancer, stroke, and venous thromboembolism.4,5 Notably, except for the divergent findings about CHD, the WHI findings were largely concordant with the observational studies (Figure). The relative risks for hip fractures and colorectal cancer with HT were reduced, whereas those for breast cancer, venous thromboembolism, and stroke were increased. At surprising odds with the observational studies, the WHI found a 29% increase in CHD after an average of 5.2 years of follow-up.1 Before the WHI, other RCTs had already begun to cast doubt on the cardiovascular benefit of HT. The Heart and Estrogen/progestin Replacement Study (HERS) had reported an …