Vascular effects of synthetic or natural progestagen combined with conjugated equine estrogen in healthy postmenopausal women.

BACKGROUND Synthetic, not natural, progestagen may negate the favorable effects of estrogen. Nonetheless, observational studies report no differences in risk for clinical cardiovascular events between users of unopposed estrogen and users of estrogen combined with synthetic progestin. METHODS AND RESULTS In a double-blind study, we randomly assigned 20 healthy postmenopausal women to micronized progesterone (MP) 200 mg or medroxyprogesterone acetate (MPA) 10 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and the remaining 5 days off cyclically during 2 months, followed by crossover to the alternate therapy. CEE+MP and CEE+MPA significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements (P=0.004 by ANOVA) by a similar degree (P=0.863). Both therapies significantly decreased E-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 levels from baseline values (P<0.001, P=0.048, and P=0.016 by ANOVA, respectively) by a similar degree (P=0.977 for ICAM-1 and P=0.541 for VCAM-1, respectively). CEE+MPA decreased E-selectin levels more than CEE+MP did (P=0.040). Both therapies significantly decreased monocyte chemoattractant protein-1 levels from baseline values (P<0.005 by ANOVA) by a similar degree (P=0.194). Both therapies significantly decreased tissue factor antigen and increased tissue factor activity levels from baseline values (P=0.003 and P<0.001 by ANOVA, respectively) by a similar degree (P=0.652 for antigen and P=0.173 for activity). Both therapies significantly lowered plasma plasminogen activator inhibitor-1 levels from baseline values (P<0.001 by ANOVA) by a similar degree (P=0.533). CONCLUSIONS CEE+MP and CEE+MPA provide similar improvement in endothelium-dependent vasodilator responsiveness and effects on markers of inflammation, hemostasis, and fibrinolysis inhibition in healthy postmenopausal women.