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

1.虽然雌激素替代疗法（ERT）具有抗动脉粥样硬化的作用，但ERT诱导的血浆甘油三酯（TG）升高可能会降低低密度脂蛋白（LDL）的大小。我们概述了雌激素诱导LDL颗粒尺寸减小的机制如下。雌激素增强肝脏TG生成。雌激素诱导的高胆固醇血症增强脂质转移反应，导致富含TG和胆固醇酯贫乏的LDL颗粒。随后通过脂解酶水解富集的TG含量可增加比正常小的LDL颗粒的形成。此外，我们评估了雌激素诱导的小LDL颗粒是否具有致动脉粥样硬化性。在雌激素诱导的血浆TG显著升高的受试者中，雌激素显著降低LDL颗粒的直径，并显著增加LDL氧化。相反，雌激素显著降低LDL氧化，但在血浆LDL水平较低的受试者中LDL颗粒直径没有显著变化。 关于我们 a雌激素治疗后TG浓度不变。由于雌激素诱导的血浆TG升高可能产生更容易氧化的小LDL颗粒，雌激素的抗氧化作用可能会在显示这种TG升高的患者中被抵消。因此，我们阐明了雌激素诱导的小LDL颗粒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，绝经后内皮功能下降，而雌激素替代疗法可使内皮功能增强。我们评估了醋酸甲羟孕酮（MPA）对接受雌激素治疗的绝经后妇女内皮功能的影响。内皮依赖性血管舒张升高，由雌激素单独，但MPA（2.5毫克，5.0毫克）逆转雌激素的浓度依赖性的方式，这种有益的效果。添加2.5 mg MPA（用于连续联合治疗的标准剂量）已经减弱了雌激素诱导的内皮依赖性血管舒张的增强作用。因此，在绝经后妇女中，同时给予MPA可能会抵消雌激素对内皮功能的有利影响。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