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Invited commentary: can selection bias explain the cardiovascular benefits of estrogen replacement therapy?

Evidence from over 30 epidemiologic studies indicates that postmenopausal women who take estrogen are at lower risk for coronary heart disease. A recent meta-analysis of all published studies found a 35 percent decrease in coronary disease (relative risk (RR) = 0.65, 95 percent confidence interval (CI) 0.60-0.70) for women who had ever used hormones compared with never users (1). Furthermore, the data suggest that most of this apparent protection is among the current hormone users; the summary relative risk for those studies that separately examined current use was 0.49 (95 percent CI 0.43-0.56) (1). Nonetheless, this consistent finding from observational studies does not prove cause and effect. It is widely recognized that women who choose to use estrogen may also make other choices that could be associated with reduced rates of heart disease (2-5). In this issue of the Journal, Matthews et al. (6) contribute to a growing body of literature that finds that, in the general population, women who are prescribed hormones often are healthier than women who are not given estrogen replacement therapy (ERT) (2, 7). In a prospective study of randomly selected premenopausal women in Pennsylvania, Matthews et al. observed a better cardiovascular risk factor profile prior to ERT among the women who subsequently took hormones at menopause than among women who did not take hormones; ERT users were better educated, had higher high density lipoprotein (HDL) cholesterol, more physical activity, and greater alcohol intake than nonusers, as well as lower apolipoprotein B, blood pressure, weight, and fasting insulin levels. Based on these differences among the subsequent hormone users and nonusers in their study population, the authors suggest that the apparent benefit of hormones