Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women

OBJECTIVES We sought to compare the effects of estrogen/transvaginal proges terone gel with estrogen/medroxyprogesterone acetate (MPA) on exercise-indu ced myocardial ischemia in postmenopausal women with coronary artery diseas e or previous myocardial infarction, or both. BACKGROUND Estrogen therapy beneficially affects exercise-induced myocardia l ischemia in postmenopausal women; however, women with an intact uterus al so take progestin to protect against uterine malignancies. The effects of c ombination estrogen/progestin therapy on myocardial ischemia are unknown. METHODS Eighteen postmenopausal women (mean +/- SD age 59 +/- 7 years) were given 17-beta-estradiol in single-blinded manner for four weeks (1 mg/day for three weeks then 2 mg/day for one week). Estradiol (2 mg/day) was then continued, and the patients were randomized (double-blind) for 12 days to e ither transvaginal progesterone gel (90 mg on alternate days) and oral MPA placebo (10 mg/day), or vice versa. After another two weeks on estradiol al one, the patients crossed over to progestin treatment and repeated the prot ocol on the opposite treatment. Patients underwent treadmill exercise testi ng after each estradiol phase and at day 10 of each progestin phase. RESULTS Exercise time to myocardial ischemia increased after the first estr ogen phase as compared with baseline (mean difference with 95% confidence i nterval [CI]: 72 s [34 to 110], p = 0.001), and was increased by combinatio n estradiol/progesterone therapy as compared with estradiol/MPA therapy (92 s [35 to 149], p = 0.001)). Two patients (11%) were withdrawn while taking estradiol/MPA owing to unstable angina. CONCLUSIONS Combination estrogen/transvaginal progesterone gel increases ex ercise time to myocardial ischemia, as compared with estrogen/MPA. These re sults imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration. (C) 2000 by the American College of Ca rdiology.