MENOPAUSAL HORMONE THERAPY AND ATHEROSCLEROTIC RISK

绝经后激素替代具有重要的公共卫生意义 因为美国有4000多万绝经后妇女 今天。年将有越来越多的妇女接受激素替代治疗 未来，因为它是预防癌症的首选治疗方法 骨质疏松症和在雌激素方案中添加孕激素 大大降低子宫内膜癌的风险 雌激素。关于激素疗法的适当配方的决定 不能仅限于它对骨骼和子宫的影响。雌激素 替换与降低冠状动脉疾病的风险有关， 可能是由于对高密度脂蛋白胆固醇的影响。然而，促孕素却是不利的 影响雌激素的有益作用，因此，可能有深远的影响 对绝经后发病率和死亡率的影响。 我们将检验单独使用雌激素和补充雌激素的效果。 对已知或可疑的冠心病危险因素使用三种促孕素。中的更改 极低密度脂蛋白、低密度脂蛋白、高密度脂蛋白以及高密度脂蛋白2的水平和组成 而HDL3亚组分和载脂蛋白A-I、A-II、B和E将是 下定决心。导致极低密度脂蛋白变化的机制的性质 而高密度脂蛋白水平将通过肝素后肝脏的测定来检测 和肝外脂蛋白脂肪酶分布的变化 极低密度脂蛋白载脂蛋白C和载脂蛋白E。上述参数的确定将 协助评估实验的结果，旨在检查 激素诱导的脂蛋白变化导致功能改变 高密度脂蛋白和极低密度脂蛋白的作用。我们将确定预期的成分是否 高密度脂蛋白的变化导致卵磷脂：胆固醇的变化 不依赖酰基转移酶的胆固醇从高密度脂蛋白到极低密度脂蛋白的转移 低密度脂蛋白。我们将进一步确定是否给予类固醇激素 改变对极低密度脂蛋白残留物的摄取和随后对脂肪酸的抑制 大鼠离体肝细胞的合成及极低密度脂蛋白残留物的清除 载脂蛋白被高密度脂蛋白改变。上述参数的更改将是 与性激素结合球蛋白水平的变化相关 性腺类固醇激素修饰雌激素活性的指示剂。类似地，这也是 提案将研究混凝的各种参数和可能的 雌激素替代的有益效果。

Postmenopausal hormone replacement is of great public health significance because there are over 40 million postmenopausal women in the United States today. Increasing numbers of women will be offered hormonal replacement in the future because it is the treatment of choice for the prevention of osteoporosis and because the addition of progestogens to estrogen regimens greatly decreases the risk of endometrial cancer associated with unopposed estrogen. Decisions regarding the proper formulation of hormonal regimens can not be limited to its effects on bone and the uterus. Estrogen replacement is associated with decreased risk of coronary artery disease, possibly due to the effect on HDL-C. Progestogens, however, adversely affect the beneficial effects of estrogen and thus, may have profound effects on postmenopausal morbidity and mortality. We will examine the effects of estrogen alone and estrogen supplemented with three progestogens on known or suspected CAD risk factors. Changes in the levels and compositions of VLDL, LDL and HDL, as well as in the HDL2 and HDL3 subfractions and apolipoproteins A-I, A-II, B and E will be determined. The nature of the mechanisms responsible for changes in VLDL and HDL levels will be examined by determination of post-heparin hepatic and extrahepatic lipoprotein lipase and of changes in the distribution of VLDL apoC and apoE proteins. Determinations of the above parameters will assist in evaluating the results of experiments designed to examine whether hormone-induced changes in lipoproteins cause changes in the functional roles of HDL and VLDL. We will determine whether expected compositional changes in HDL cause changes in the lecithin: cholesterol acyltransferase-independent transfer of cholesterol from HDL to VLDL and LDL. We will further determine whether steroidal hormone administration changes the uptake of VLDL remnants and subsequent inhibition of fatty acid synthesis in isolated rat hepatocytes and if the removal of VLDL remnant apoC proteins by HDL is altered. Changes in the above parameters will be correlated with changes in levels of sex hormone binding globulin as an indicator of gonadal steroid modified estrogenicity. Similarly this proposal will study various parameters of coagulation and the possible beneficial effects of estrogen replacement.