This aim of this clinical study was to compare the effects of estrogen + transvaginal progesterone gel against estrogen + oral medroxyprogesterone acetate (MPA) on exercise-induced myocardial ischemia in post-menopausal women with coronary artery disease (CAD) or previous myocardial infarction, or both. Estrogen hormone therapy is beneficial to post-menopausal women with exercise-induced myocardial ischemia. Prior to this study the effects of combining estrogen with progestin therapy were unknown. The results from this clinical study indicate that by adding natural progesterone gel to estradiol treatment, there was an increase in exercise time to myocardial ischemia compared to estradiol therapy alone. The addition of MPA to estradiol therapy had no effect on exercise time to myocardial ischemia. Overall, the results indicate that estrogen and progesterone together have a synergistic effect on exercise time to myocardial ischemia, but this is not replicated with the combination of estrogen and MPA.