Objective A considerable number of postmenopausal women who receive estrogen therapy (ET) are also treated for hypercholesterolemia with cholesterol-lowering statins. Statins and steroid hormones can compete for the same steroid-metabolizing enzymes. We investigated whether long-term administration of statins had an effect on serum estrogen and androgen levels in postmenopausal women receiving and not receiving oral ET. Methods A subgroup analysis from the Estrogen in the Prevention of Atherosclerosis Trial, a randomized, double-blind, placebo-controlled trial, was performed. A total of 222 women were randomized to receive either placebo or 1 mg of oral micronized E2 daily for 2 years. In both the placebo and treatment groups, participants with LDL-cholesterol levels >160 mg/dL were treated with statins. Blood samples were obtained at baseline and every 6 months during the trial. Serum levels of DHEA, androstenedione, testosterone, estrone and E2 were measured by RIA. Results Among 86 placebo- and 90 estradiol-treated subjects with baseline and on-trial hormone measurements, no significant differences were observed between the statin-free and statin-treated groups in mean changes from baseline to on-trial levels in any of the androgens or estrogens, whether or not the postmenopausal women were treated with estrogen. Conclusion The results suggest that ET and statins can be used simultaneously with no deleterious effects on circulating hormone levels.