Invited Commentary: How Far Can Epidemiologists Get with Statistical Adjustment

In 2002, the Women’s Health Initiative (WHI) clinical trial reported that combined estrogen-plus-progestin hor-mone therapy did not prevent coronary heart disease in women (1). Combined estrogen-plus-progestin therapy in-creased the risk of stroke by a factor of 1.4 on average and doubled the risk of venous thromboembolism. Observational research up to the time of the WHI sug-gested that the relative risk of coronary heart disease was 0.50–0.65 in hormone users compared with nonusers (2, 3). Based on observational research, the relative risk of stroke was considered less than or near 1.0 for hormone therapy (2). Both observational studies (4) and a randomized trial, the Heart Estrogen/progestin Replacement Study (HERS) (5), showed a relative risk of 1–2 for venous thromboembolism in hormone users