Hormone replacement therapy and prevention of coronary heart disease in postomenopausal women.

1.雌激素替代疗法(ERT)虽然具有抗动脉粥样硬化的作用，但雌激素替代疗法引起的血浆甘油三酯(TG)升高可能使低密度脂蛋白(LDL)变小。我们概述了雌激素诱导的低密度脂蛋白颗粒尺寸减小的机制如下。雌激素促进肝脏甘油三酯的产生。雌激素诱导的高甘油三酯血症增强了脂质转移反应，导致富含甘油三酯而缺乏胆固醇酯的低密度脂蛋白颗粒。随后脂解酶对浓缩的甘油三酯进行水解，可能会增加比正常水平更小的低密度脂蛋白颗粒的形成。此外，我们还评估了雌激素诱导的小颗粒低密度脂蛋白是否会导致动脉粥样硬化。在雌激素诱导的血浆甘油三酯大幅升高的受试者中，雌激素显著减小低密度脂蛋白颗粒的直径，并显著增加低密度脂蛋白的氧化。相反，雌激素显著减少低密度脂蛋白的氧化，对血浆…的受试者的低密度脂蛋白颗粒直径没有显著影响此外，雌激素治疗后，甘油三酯浓度没有变化。由于雌激素诱导的血浆甘油三酯升高可能会产生更容易氧化的细小低密度脂蛋白颗粒，因此在出现这种甘油三酯升高的患者中，雌激素的抗氧化作用可能会被抵消。因此，我们阐明了雌激素诱导的小颗粒低密度脂蛋白是致动脉粥样硬化的。内皮功能与动脉粥样硬化的发生发展密切相关，已有报道绝经后内皮功能下降，而ERT则使内皮功能增强。我们评价了醋酸甲羟孕酮(MPA)对接受雌激素治疗的绝经后妇女血管内皮功能的影响。单用雌激素可增强内皮依赖性血管扩张，但加入甲孕酮(2.5 mg、5.0 mg)可浓度依赖性地逆转雌激素的这一有利作用。在连续联合治疗中使用的标准剂量添加2.5毫克的甲孕酮，已经减弱了雌激素诱导的内皮依赖性血管扩张的增强。因此，同时给药可能抵消雌激素对绝经后妇女内皮功能的有利影响。较少

1. Although estrogen replacement therapy (ERT) has anti-atherogenic effects, ERT-induced increase in plasma triglyceride (TG) may reduce the size of low-density lipoprotein (LDL). We outlined the mechanism of the estrogen-induced decrease in LDL particle size as follows. Estrogen enhances hepatic TG production. Estrogen-induced hypertriglyceridemia enhances lipid transfer reactions, resulting in TG-rich and cholesterol ester-poor LDL particles. Subsequent hydrolysis of the enriched TG content by lipolytic enzymes may increase the formation of LDL particles that are smaller than normal. In addition, we evaluated whether estrogen-induced small LDL particles are atherogenic. In subjects with substantial estrogen-induced plasma TG increases, estrogen significantly reduced the diameter of LDL particles, and significantly increased the LDL oxidation. In contrast, estrogen significantly reduced the LDL oxidation and caused no significant change in LDL particle diameter in subjects whose plasm … More a TG concentration was unchanged with estrogen therapy. Because estrogen-induced plasma TG increases may produce small LDL particles that are more susceptible to oxidation, antioxidant effects of estrogen might be offset in patients showing such a TG increase. Thus, we clarified that estrogen-induced small LDL particles are atherogenic.2. Endothelial function which is closely related with development of atherosclerosis, has been reported to decrease after menopause, but increase by ERT. We evaluated the effect of medroxyprogesterone acetate (MPA) on endothelial function in postmenopausal women receiving estrogen. Endothelium-dependent vasodilation was elevated by estrogen alone, but addition of MPA (2.5 mg, 5.0 mg) reversed this beneficial effect of estrogen in a concentration dependent manner. Addition of MPA at 2.5 mg the standard dose used for continuous combined therapy, already attenuates estrogen-induced enhancement of endothelium-dependent vasodilation. Accordingly, concurrent MPA administration may offset favorable effects of estrogen on endothelial function in postmenopausal women. Less