Gerhard M, Walsh B W, Tawakol A, Haley E A, Creager S J, Seely E W, Ganz P, Creager M A
Department of Medicine, Obstetrics and Gynecology , Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Circulation. 1998 Sep 22;98(12):1158-63. doi: 10.1161/01.cir.98.12.1158.
Epidemiological studies indicate that estrogen replacement therapy decreases the risk of cardiovascular events in postmenopausal women. Estrogen may confer cardiovascular protection by improving endothelial function because it increases endothelium-dependent vasodilation. It is not known whether progesterone attenuates the beneficial effects of estrogen on endothelial function.
Seventeen postmenopausal women with mild hypercholesterolemia were enrolled in a placebo-controlled, crossover trial to evaluate the effect of transdermal estradiol, with and without vaginal micronized progesterone, on endothelium-dependent vasodilation in a peripheral conduit artery. Brachial artery diameter was measured with high-resolution B-mode ultrasonography. To assess endothelium-dependent vasodilation, brachial artery diameter was determined at baseline and after a flow stimulus induced by reactive hyperemia. To assess endothelium-independent vasodilation, brachial artery diameter was measured after administration of sublingual nitroglycerin. During estradiol therapy, reactive hyperemia caused an 11.1+/-1.0% change in brachial artery diameter compared with 4. 7+/-0.6% during placebo therapy (P<0.001). Progesterone did not significantly attenuate this improvement. During combined estrogen and progesterone therapy, flow-mediated vasodilation of the brachial artery was 9.6+/-0.8% (P=NS versus estradiol alone). Endothelium-independent vasodilation was not altered by estradiol therapy, either with or without progesterone, compared with placebo. There was a modest decrease in total and LDL cholesterol during treatment both with estradiol alone and when estradiol was combined with progesterone (all P<0.001 versus placebo). In a multivariate analysis that included serum estradiol, progesterone, total and LDL cholesterol concentrations, blood pressure, and heart rate, only the estradiol level was a significant predictor of endothelium-dependent vasodilation.
The addition of micronized progesterone does not attenuate the favorable effect of estradiol on endothelium-dependent vasodilation. The vasoprotective effect of hormone replacement therapy may extend beyond its beneficial actions on lipids.
流行病学研究表明，雌激素替代疗法可降低绝经后女性心血管事件的风险。雌激素可能通过改善内皮功能来提供心血管保护，因为它可增加内皮依赖性血管舒张。目前尚不清楚孕激素是否会减弱雌激素对内皮功能的有益作用。
17名患有轻度高胆固醇血症的绝经后女性参与了一项安慰剂对照的交叉试验，以评估经皮雌二醇（无论有无阴道微粒化孕酮）对外周导管动脉内皮依赖性血管舒张的影响。采用高分辨率B型超声测量肱动脉直径。为评估内皮依赖性血管舒张，在基线时以及反应性充血诱导的血流刺激后测定肱动脉直径。为评估非内皮依赖性血管舒张，在舌下含服硝酸甘油后测量肱动脉直径。在雌二醇治疗期间，反应性充血导致肱动脉直径变化11.1±1.0%，而安慰剂治疗期间为4.7±0.6%（P<0.001）。孕激素并未显著减弱这种改善。在雌激素和孕激素联合治疗期间，肱动脉的血流介导的血管舒张为9.6±0.8%（与单独使用雌二醇相比，P=无显著性差异）。与安慰剂相比，无论有无孕激素，雌二醇治疗均未改变非内皮依赖性血管舒张。单独使用雌二醇治疗以及雌二醇与孕激素联合治疗期间，总胆固醇和低密度脂蛋白胆固醇均有适度下降（与安慰剂相比，所有P<0.001）。在一项包括血清雌二醇、孕激素、总胆固醇和低密度脂蛋白胆固醇浓度、血压和心率的多变量分析中，只有雌二醇水平是内皮依赖性血管舒张的显著预测因子。
添加微粒化孕酮不会减弱雌二醇对内皮依赖性血管舒张的有利作用。激素替代疗法的血管保护作用可能超出其对脂质的有益作用。
