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 eff ects of estrogen, Nonetheless, observational studies report no differences in risk for clinical cardiovascular events between users of unopposed estro gen and users of estrogen combined with synthetic progestin. Methods and Results-in a double-blind study, we randomly assigned 20 health y postmenopausal women to micronized progesterone (MP) 200 mg or medroxypro gesterone 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 hypere mia relative to baseline measurements (P=0.004 by ANOVA) by a similar degre e (P=0.863). Both therapies significantly decreased E-selectin, intercellul ar 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, respe ctively) by a similar degree (P=0.977 for ICAM-1 and P=0.541 for VCAM-1, re spectively). CEE+MPA decreased E-selectin levels more than CEE+MP did (P=0. 040). Both therapies significantly decreased monocyte chemoattractant prote in-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 in creased 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 plasminog en 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-d ependent vasodilator responsiveness and effects on markers of inflammation, hemostasis, and fibrinolysis inhibition in healthy postmenopausal women.