Effect of Medroxyprogesterone Acetate on Endothelium-Dependent Vasodilation in Postmenopausal Women Receiving Estrogen

Effect of Medroxyprogesterone Acetate on Endothelium-Dependent Vasodilation in Postmenopausal Women Receiving Estrogen
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醋酸甲羟孕酮对接受雌激素的绝经后妇女内皮依赖性血管舒张的影响

DOI:
10.1161/hc4001.097035
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发表时间:
2001
期刊:
Circulation: Journal of the American Heart Association
影响因子:
--
通讯作者:
T. Fukaya
T. Fukaya
中科院分区:
--
文献类型:
--
作者:
A. Wakatsuki;Y. Okatani;N. Ikenoue;T. Fukaya

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背景:雌激素增加绝经后妇女内皮依赖性血管舒张。然而,黄体酮与雌激素联合使用可能会抵消雌激素对内皮细胞的有益作用。我们研究了醋酸甲羟孕酮(MPA)对绝经后妇女雌激素诱导的内皮依赖性血管舒张增加的影响。方法与结果:绝经后妇女每日应用共轭马雌激素(CEE) 0.625 mg (n=14)、CEE 0.625 mg + MPA 2.5 mg (n=15)或CEE 0.625 mg + MPA 5.0 mg (n=16)治疗3个月。治疗前后测定血脂和激素水平。利用高分辨率超声测量血流介导的血管舒张(FMD)和硝酸甘油诱导的血管舒张,评估肱动脉的血管舒张反应。用CuSO4孵育分析LDL对氧化的敏感性,同时监测共轭二烯形成的动力学。各组患者血浆总胆固醇和低密度脂蛋白胆固醇浓度均显著降低。CEE显著增加口蹄疫,从4.5±1.7%增加到8.5±2.8% (P <0.001)。MPA的加入以浓度依赖性的方式逆转了这一效应(MPA 2.5 mg,从5.0±3.2%到6.2±3.1%;MPA 5.0 mg,从4.9±3.4%到3.6±3.7%;P =NS)。没有治疗显著改变硝酸甘油诱导的扩张。各处理组共轭二烯形成滞后时间均显著延长,氧化速率显著降低。结论:同时给予MPA可能会抵消雌激素对绝经后妇女内皮功能的有利作用。由于MPA不降低雌激素的降LDL和抗氧化作用,MPA诱导的内皮依赖性血管舒张抑制可能不依赖于氧化敏感性和血浆LDL浓度的变化。
Background—Estrogen increases endothelium-dependent vasodilation in postmenopausal women. However, use of progestins in combination with estrogen may counter beneficial effects of estrogen on endothelium. We investigated the effect of medroxyprogesterone acetate (MPA) on estrogen-induced increase in endothelium-dependent vasodilation in postmenopausal women. Methods and Results—Postmenopausal women were treated daily with conjugated equine estrogen (CEE) 0.625 mg (n=14), CEE 0.625 mg and MPA 2.5 mg (n=15) or CEE 0.625 mg and MPA 5.0 mg (n=16) for 3 months. Plasma lipids and hormones were measured before and after treatment. Vasodilatory responses of the brachial artery were evaluated by measuring flow-mediated vasodilation (FMD) and nitroglycerin-induced vasodilation by use of high-resolution ultrasonography. Susceptibility of LDL to oxidation was analyzed by incubation with CuSO4 while kinetics of conjugated diene formation was monitored. Plasma total and LDL cholesterol concentrations were decreased significantly in all groups. CEE increased FMD significantly, from 4.5±1.7% to 8.5±2.8% (P <0.001). Addition of MPA reversed this effect in a concentration-dependent manner (for MPA 2.5 mg, from 5.0±3.2% to 6.2±3.1%; for MPA 5.0 mg, from 4.9±3.4% to 3.6±3.7%;P =NS for each). No treatment significantly altered nitroglycerin-induced dilation. Lag time for conjugated diene formation was prolonged significantly in all groups, and the oxidation rate was significantly reduced. Conclusions—Concurrent MPA administration may offset favorable effects of estrogen on endothelial function in postmenopausal women. Because MPA did not diminish LDL-lowering and antioxidant effects of estrogen, MPA-induced inhibition of endothelium-dependent vasodilation may be independent of changes in oxidative susceptibility and plasma concentration of LDL.
DOI: 10.1161/01.cir.81.2.491
发表时间: 1990-02-01
期刊: CIRCULATION
影响因子: 37.8
作者:
VITA, JA;TREASURE, CB;GANZ, P
通讯作者: GANZ, P
DOI: 10.1161/01.atv.17.1.217
发表时间: 1997-01-01
影响因子: 8.7
作者:
Adams, MR;Register, TC;Williams, JK
通讯作者: Williams, JK
抗孕激素治疗期间雌激素在恒河猴生殖道中的作用。
DOI: 10.1210/endo.132.4.8462480
发表时间: 1993
期刊: Endocrinology
影响因子: 4.8
作者:
Slayden,OD;Hirst,JJ;Brenner,RM
通讯作者: Brenner,RM
DOI: 10.1073/pnas.91.11.5212
发表时间: 1994-05-24
影响因子: 11.1
作者:
WEINER, CP;LIZASOAIN, I;MONCADA, S
通讯作者: MONCADA, S