Medroxyprogesterone acetate prevents the cardioprotective and anti-inflammatory effects of 17β-estradiol in an in vivo model of myocardial ischemia and reperfusion

Previous studies demonstrated the protective effects of estrogen administration in models of cardiovascular disease. However, there is a discrepancy between these data and those from the recent clinical trials with hormone replacement therapy in menopausal women. One possible explanation for the divergent results is the addition of progestin to the hormone regimen in the Women's Health Initiative and the Heart and Estrogen/Progestin Replacement Study trials. The aim of the present study was to examine the effects of a combination of 17 beta-estradiol (E-2, 20 mu g) and medroxyprogesterone acetate (MPA, 80 mu g) on infarct size in New Zealand White rabbits. Infarct size as a percentage of the area at risk was significantly reduced by administration of E2 30 min before induction of myocardial ischemia compared with vehicle (19.5 +/- 3.1 vs. 55.7 +/- 2.6%, P < 0.001). However, E-2 + MPA failed to elicit a reduction in infarct size (52.5 +/- 4.6%), and MPA had no effect (50.8 +/- 2.6%). E-2 also reduced serum levels of cardiac troponin I, immune complex deposition in myocardial tissue, activation of the complement system, and lipid peroxidation. All these effects were reversed by MPA. The results suggest that MPA antagonizes the infarct-sparing effects of E-2, possibly through modulation of the immune response after ischemia and reperfusion.