Estrogen replacement therapy and mortality among older women: The study of osteoporotic fractures

Background: Most previous studies of estrogen replacement therapy (ERT) and mortality have focused on younger women. Recently, it has been suggested that the effect of ERT on mortality may represent a 'healthy-user' effect, ie, those with healthier lifestyles having a greater likelihood of receiving ERT. Methods: Nine thousand seven hundred four women, 65 years or older, participated; 1258 (14.1%) reported current use of ERT for at least 1 year at entry. During an average follow-up of 6.0 years, 1054 women (11.8%) died. Results: After adjusting for multiple variables, mortality rate was lower among current (relative risk [RR], 0.69; 95% confidence interval [CI], 0.54- 0.87) and past users (RR, 0.79; 95% CI, 0.66-0.95), mainly due to reductions in deaths due to cardiovascular disease. The protective effect of ERT was greatest among women younger than 75 years (RR, 0.55; 95% CI, 0.40-0.76) compared with women from 75 to 84 years of age (RR, 0.93; 95% CI, 0.62-1.41) and 85 years or older (RR, 1.33; 95% CI, 0.43-4.12). The RR for overall mortality was 0.95 (95% CI, 0.68-1.32) among short-term users (1-9 years) compared with 0.55 (95% CI, 0.40-0.75) among long-term users (≤ 10 years). Deaths considered unrelated to ERT tended also to be reduced in current users younger than 75 years (RR, 0.72; 95% CI, 0.49-1.06) and current long-term users (RR, 0.75; 95% CI, 0.51-1.10). Conclusions: Estrogen replacement therapy is associated with lower overall mortality rates and reduced deaths due to cardiovascular disease. Women using ERT had healthier lifestyles, and the risk for death thought to be unrelated to ERT also tended to be lower in ERT users, suggesting in part a healthy-user effect.