MENOPAUSAL HORMONE THERAPY AND ATHEROSCLEROTIC RISK

绝经后激素替代具有重要的公共卫生意义 因为在美国有超过四千万绝经后的妇女 今天 越来越多的妇女将在2010年接受激素替代治疗。 未来，因为它是治疗的选择， 骨质疏松症，因为在雌激素治疗方案中加入孕激素 大大降低了子宫内膜癌的风险， 雌激素. 关于适当制定激素方案的决定 不仅限于对骨骼和子宫的影响。 雌激素 置换与冠状动脉疾病风险降低相关， 可能是由于对HDL-C的影响。 然而，孕激素却有不利作用 影响雌激素的有益作用，因此， 对绝经后发病率和死亡率的影响 我们将研究单独雌激素和补充雌激素的影响 已知或疑似CAD风险因素的三种孕激素。 变化 VLDL、LDL和HDL的水平和组成，以及HDL 2 和HDL 3亚组分和载脂蛋白A-I、A-II、B和E将被 测定 负责VLDL变化的机制的性质 和HDL水平将通过测定肝素后肝 和肝外脂蛋白脂酶的分布变化， VLDL apoC和apoE蛋白。 上述参数的确定将 协助评估旨在检查是否 脂肪酸诱导的脂蛋白变化引起功能性 HDL和VLDL的作用 我们将确定预期的成分 高密度脂蛋白的变化引起卵磷脂的变化：胆固醇 胆固醇从HDL向VLDL的酰基转移酶非依赖性转移， 低密度脂蛋白 我们将进一步确定是否类固醇激素管理 改变极低密度脂蛋白残余物的摄取和随后的脂肪酸抑制 在分离的大鼠肝细胞中的VLDL合成， apoC蛋白质被HDL改变。 上述参数的更改将 与性激素结合球蛋白水平的变化相关， 性腺类固醇修饰雌激素活性的指标。 同样， 建议将研究各种参数的混凝和可能的 雌激素替代的好处

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.