Women's Health Initiative Hormone Therapy Trials

Abstract The Women's Health Initiative (WHI) postmenopausal hormone therapy (HT) trials were designed to determine the balance of benefits and risks of HT taken for chronic disease prevention by initially healthy postmenopausal women (age range, 50—79 years; mean age, 63 years). Women with an intact uterus were randomized to estrogen–progestin or placebo for a mean of 5.6 years; women with hysterectomy were randomized to estrogen alone or placebo for a mean of 7.1 years. Compared with their respective placebo‐group counterparts, women in the estrogen–progestin group were significantly more likely to experience an adverse health event, whereas women in the estrogen‐alone group were as likely to do so. Specifically, estrogen–progestin was associated with increased risks of coronary heart disease (CHD), stroke, venous thromboembolism, and breast cancer, as well as reduced risks of hip fracture and colorectal cancer. Estrogen alone was associated with an increased risk of stroke and a reduced risk of hip fracture; it had no effect on CHD risk. The results do not support the use of HT for chronic disease prevention in postmenopausal women as a whole. However, because few WHI participants were within 5 years of menopause, these trials cannot conclusively determine the risk–benefit balance of HT in recently menopausal women. Accumulating data suggest that the timing of HT initiation in relation to age or menopause onset may critically influence the relationship between such therapy and risk of CHD as well as its overall risk–benefit balance, with younger or recently menopausal women experiencing more favorable effects than older women or women further from menopause.