OBJECTIVE: We observed that estrogen did not show cardioprotective benefits in type 2 diabetic postmenopausal women. We hypothesized that hypertensive and/or overweight women may be less likely to realize cardiovascular benefits from estrogen. METHODS AND RESULTS: We administered micronized progesterone (MP) 100 mg or medroxyprogesterone acetate (MPA) 2.5 mg with conjugated equine estrogen (CEE) 0.625 mg daily during 2 months to 35 hypertensive and/or overweight postmenopausal women with a randomized, double-blind, crossover design. With significant changes of lipoproteins, CEE+MP or MPA significantly improved flow-mediated dilation and reduced plasma E-selectin, intercellular adhesion molecule type-1, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha levels (P<0.001, P<0.001, P=0.021, P<0.001, and P<0.001 by ANOVA, respectively), but not C-reactive protein and fibrinogen levels. Of note, there were no significant differences between each therapy regarding these effects. However, the magnitude of improvement of flow-mediated dilation in these women was less than in healthy postmenopausal women and more than in diabetic postmenopausal women reported by our previous studies. The effects of CEE+MP or MPA on inflammatory markers were comparable to healthy postmenopausal women, but not comparable to diabetic postmenopausal women. CONCLUSIONS:Estrogen combined with synthetic progestin significantly improved flow-mediated brachial artery dilator response and reduced inflammation markers in hypertensive and/or overweight women, comparable to estrogen combined with natural progesterone.
RCT Entities:
OBJECTIVE: We observed that estrogen did not show cardioprotective benefits in type 2 diabetic postmenopausal women. We hypothesized that hypertensive and/or overweight women may be less likely to realize cardiovascular benefits from estrogen. METHODS AND RESULTS: We administered micronized progesterone (MP) 100 mg or medroxyprogesterone acetate (MPA) 2.5 mg with conjugated equine estrogen (CEE) 0.625 mg daily during 2 months to 35 hypertensive and/or overweight postmenopausal women with a randomized, double-blind, crossover design. With significant changes of lipoproteins, CEE+MP or MPA significantly improved flow-mediated dilation and reduced plasma E-selectin, intercellular adhesion molecule type-1, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha levels (P<0.001, P<0.001, P=0.021, P<0.001, and P<0.001 by ANOVA, respectively), but not C-reactive protein and fibrinogen levels. Of note, there were no significant differences between each therapy regarding these effects. However, the magnitude of improvement of flow-mediated dilation in these women was less than in healthy postmenopausal women and more than in diabetic postmenopausal women reported by our previous studies. The effects of CEE+MP or MPA on inflammatory markers were comparable to healthy postmenopausal women, but not comparable to diabetic postmenopausal women. CONCLUSIONS: Estrogen combined with synthetic progestin significantly improved flow-mediated brachial artery dilator response and reduced inflammation markers in hypertensive and/or overweight women, comparable to estrogen combined with natural progesterone.