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

绝经后妇女的激素替代治疗和冠心病的预防。

• 批准号: 12671607
• 负责人: WAKATSUKI Akihiko
• 金额: $ 2.05万
• 依托单位: Kochi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671607/
• 关键词: Postmenopausal Women; estrogen; medroxyprogesterone; LDL particle diameter; LDL oxidation; endothelial function; 小粒子LDL; 脂質転送; リパーゼ

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

1. 虽然雌激素替代疗法（ERT）具有抗动脉粥样硬化作用，但ERT引起的血浆甘油三酯（TG）增加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 粒径减小的机制如下。雌激素可增强肝脏 TG 的产生。雌激素诱导的高甘油三酯血症会增强脂质转移反应，产生富含 TG 和缺乏胆固醇酯的 LDL 颗粒。随后，脂肪分解酶对富含 TG 的水解可能会增加比正常情况更小的 LDL 颗粒的形成。此外，我们还评估了雌激素诱导的低密度脂蛋白小颗粒是否会导致动脉粥样硬化。在雌激素引起的血浆TG显着增加的受试者中，雌激素显着降低了LDL颗粒的直径，并显着增加了LDL氧化。相比之下，雌激素显着减少了 LDL 氧化，并且在雌激素治疗后血浆 TG 浓度没有变化的受试者中，LDL 粒径没有发生显着变化。由于雌激素诱导的血浆 TG 增加可能会产生更容易氧化的小 LDL 颗粒，因此在出现 TG 增加的患者中，雌激素的抗氧化作用可能会被抵消。由此，我们阐明雌激素诱导的小LDL颗粒具有致动脉粥样硬化作用。2．内皮功能与动脉粥样硬化的发展密切相关，据报道，内皮功能在绝经后下降，但通过ERT而增加。我们评估了醋酸甲羟孕酮 (MPA) 对接受雌激素的绝经后妇女内皮功能的影响。单独使用雌激素可提高内皮依赖性血管舒张作用，但添加 MPA（2.5 mg、5.0 mg）以浓度依赖性方式逆转雌激素的这种有益作用。添加 2.5 mg 的 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。因此，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影响。较少的

项目成果

Akihiko Wakatsuki et al.: "Lipolytic enzyme effect on small low-density lipoprotein particles in women treated with estrogen"Obstet Gynecol. 97. 333-337 (2001)

Akihiko Wakatsuki 等人：“脂肪分解酶对接受雌激素治疗的女性低密度脂蛋白小颗粒的影响”Obstet Gynecol。

Akihiko Wakatsuki et al.: "Effect of medroxyprogesterone acetate on vascular inflammatory markers in postmenopausal women receiving estrogen"Circulation. (in press).

Akihiko Wakatsuki 等人：“醋酸甲羟孕酮对接受雌激素的绝经后妇女血管炎症标志物的影响”循环。

Nobuo Ikenoue: "Small low-density lipoprotein particles in women with natural or surgically induced menopause"Obstet Gynecol. 93. 566-570 (1999)

Nobuo Ikenoue：“自然或手术引起的更年期女性的低密度脂蛋白小颗粒”Obstet Gynecol。

Akihiko Wakatsuki: "Estrogen-induced small low density lipoprotein particles may be atherogenic in postmenopausal women"J Am Coll Cardiol. 37. 425-430 (2001)

Akihiko Wakatsuki：“雌激素诱导的低密度脂蛋白小颗粒可能会导致绝经后女性动脉粥样硬化”J Am Coll Cardiol。

Akihiko Wakatsuki: "Lipolytic enzyme effect on small low-density lipoprotein particles in women treated with estrogen."Obstet.Gynecol.. 97. 333-337 (2001)

Akihiko Wakatsuki：“脂肪分解酶对接受雌激素治疗的女性低密度脂蛋白小颗粒的影响。”Obstet.Gynecol.. 97. 333-337 (2001)