OVARIECTOMY, HORMONE REPLACEMENT AND ATHEROSCLEROSIS

文献表明，口服雌激素替代品具有 对血浆脂质和脂蛋白的有益影响（降低LDL， 增加HDL），而非肠道给药的雌激素很少或没有 醋酸甲羟孕酮可能具有额外 有益的影响。 然而，雌孕激素的影响 替代疗法对绝经后女性动脉粥样硬化程度的影响 不明 本研究的一个目的是评估 绝经后激素替代治疗对动脉粥样硬化危险因素的影响 脂质、载脂蛋白、脂蛋白、血压、葡萄糖耐量，以及 某些行为和心理社会因素。 其他目标是 评估激素替代治疗对以下方面的影响：1）肝素后脂肪酶 活性; 2）性激素结合球蛋白的结合能力， 是治疗的相对雌激素活性的指标;和3） 胰岛素和胰高血糖素对静脉内葡萄糖刺激的反应。 的 本研究的主要目的是评估两种 常用的口服雌激素替代品 结合马雌激素（倍美力）或胃肠外给药 雌二醇，单独使用或与常用处方药 孕激素，醋酸甲羟孕酮（Provera）对主动脉的影响， 冠状动脉、股动脉、颅内外动脉粥样硬化 绝经期（卵巢切除）食蟹猴喂食致动脉粥样硬化饮食， 三年 动脉粥样硬化将在以下时间进行形态定量： 尸检 这项研究的结果应该提供有价值的证据， 这两种类型的雌激素替代单独或 联合醋酸甲羟孕酮对动脉粥样硬化程度的影响。 此外，将获得有关血浆脂质作用的证据 以及脂蛋白和其他危险因素介导这种影响。 长期目标是确定损害或 卵巢功能丧失影响动脉粥样硬化形成及其危险因素， 确定绝经后激素的类型和剂量水平， 更换与最佳受益和最小风险相关。

The literature suggests that orally-administered estrogen replacement has a beneficient influence on plasma lipids and lipoproteins (decreased LDL, increased HDL) while parenterally-administered estrogen has little or no effect; and that medroxyprogesterone acetate may have an additional beneficient influence. However, the influence of estrogen-progestogen replacement therapy on extent of atherosclerosis in postmenopausal females is unknown. One objective of this study is to assess the effects of postmenopausal hormone replacement on atherosclerosis risk factors: plasma lipids, apoproteins, lipoproteins, blood pressure, glucose tolerance, and certain behavioral and psychosocial factors. Additional objectives are to assess the effects of hormone replacement on: 1) postheparin lipase activities; 2) the binding capacity of sex hormone binding globulin, which is an indicator of the relative estrogenicity of the treatments; and 3) insulin and glucagon responses to an intravenous glucose challenge. The principal objective of this study is to assess the effects of two commonly-prescribed types of estrogen replacement, orally administered conjugated equine estrogens (Premarin) or parenterally-administered estradiol, alone or in combination with a frequently prescribed progestogen, medroxyprogesterone acetate (Provera) on extent of aortic, coronary, femoral, extra- and intracranial artery atherosclerosis in menopausal (ovariectomized) cynomolgus monkeys fed an atherogenic diet for three years. Atherosclerosis will be quantitated morphometrically at necropsy. The results of this study should provide valuable evidence regarding the influence of these two types of estrogen replacement alone or in combination with medroxyprogesterone acetate on extent of atherosclerosis. Additionally, evidence will be obtained regarding the role of plasm lipids and lipoproteins and other risk factors in mediating such an influence. Long term objectives are to determine mechanisms by which impairment or loss of ovarian function influence atherogenesis and its risk factors, and to determine what types and dosage levels of postmenopausal hormonal replacement are associated with optimal benefit and minimal risk.