Effect of Medroxyprogesterone Acetate on Endothelium-Dependent Vasodilation in Postmenopausal Women Receiving Estrogen

BACKGROUND: Estrogen increases endothelium-dependent vasodilation in postmenopausal women. However, use of progestins in combination with estrogen may counter beneficial effects of estrogen on endothelium. We investigated the effect of medroxyprogesterone acetate (MPA) on estrogen-induced increase in endothelium-dependent vasodilation in postmenopausal women. METHODS AND RESULTS: Postmenopausal women were treated daily with conjugated equine estrogen (CEE) 0.625 mg (n=14), CEE 0.625 mg and MPA 2.5 mg (n=15) or CEE 0.625 mg and MPA 5.0 mg (n=16) for 3 months. Plasma lipids and hormones were measured before and after treatment. Vasodilatory responses of the brachial artery were evaluated by measuring flow-mediated vasodilation (FMD) and nitroglycerin-induced vasodilation by use of high-resolution ultrasonography. Susceptibility of LDL to oxidation was analyzed by incubation with CuSO(4) while kinetics of conjugated diene formation was monitored. Plasma total and LDL cholesterol concentrations were decreased significantly in all groups. CEE increased FMD significantly, from 4.5+/-1.7% to 8.5+/-2.8% (P<0.001). Addition of MPA reversed this effect in a concentration-dependent manner (for MPA 2.5 mg, from 5.0+/-3.2% to 6.2+/-3.1%; for MPA 5.0 mg, from 4.9+/-3.4% to 3.6+/-3.7%; P=NS for each). No treatment significantly altered nitroglycerin-induced dilation. Lag time for conjugated diene formation was prolonged significantly in all groups, and the oxidation rate was significantly reduced. CONCLUSIONS: Concurrent MPA administration may offset favorable effects of estrogen on endothelial function in postmenopausal women. Because MPA did not diminish LDL-lowering and antioxidant effects of estrogen, MPA-induced inhibition of endothelium-dependent vasodilation may be independent of changes in oxidative susceptibility and plasma concentration of LDL.