ESTROGENS, BODY FAT AND DYSLIPIDEMIA AT MENOPAUSE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。在发达国家，冠心病是妇女死亡的主要原因，更年期似乎会导致冠心病风险的加速。拟议研究的目的是进一步表征绝经期脂质代谢的变化，并调查这些脂质变化的机制。中年胆固醇研究是一项前瞻性纵向研究（n=120），旨在研究1）雌激素缺乏（观察组）和2）雌激素替代治疗（ERT）（干预组）对脂质代谢的影响。绝经前的妇女作为对照组，使我们能够区分衰老和雌激素缺乏对脂质代谢的影响。在干预组中，从绝经前过渡到绝经后的妇女（n=48）被随机分配到一项交叉研究，比较短期口服和经皮雌激素对脂质代谢的影响。我们将1）确定脂质代谢蛋白（CETP和PLTP）和雄激素对绝经后出现致动脉粥样硬化脂质谱的贡献，2）确定绝经是否导致HDL颗粒亚类谱的致动脉粥样硬化转变，3）评估中心脂肪蓄积对绝经后胰岛素敏感性变化的影响。此外，通过短期经皮和口服ERT逆转脂质异常，介入组将使我们能够确认脂质代谢变化的潜在机制。这项研究是独特的设计，以回答有关绝经期的脂质代谢，雌激素作用和妇女心血管疾病的风险变化的问题。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Coronary heart disease (CHD) is the leading cause of death among women in developed countries and menopause appears to result in an acceleration of CHD risk. The objectives of the proposed study are to further characterize the menopausal changes in lipid metabolism and to investigate the mechanisms underlying these lipid changes. The Midlife Cholesterol Study is a prospective, longitudinal study (n=120) designed to investigate the effects of 1) estrogen deficiency (observational arm) and 2) estrogen replacement therapy (ERT) (interventional arm) on lipid metabolism. Women who remain premenopausal will act as control subjects, allowing us to separate the effects of aging from estrogen deficiency on lipid metabolism. In the interventional arm, women who transitioned from pre- to postmenopause (n=48) were randomized to a cross-over study comparing the effects of short-term oral and transdermal estrogen on lipid metabolism. We will 1) establish the contribution of proteins of lipid metabolism (CETP and PLTP) and androgens to the menopausal emergence of an atherogenic lipid profile, 2) determine whether menopause leads to an atherogenic shift in HDL particle subclass profile and 3) assess the influence of central fat accumulation on menopausal changes in insulin sensitivity. Furthermore, the interventional arm will allow us to confirm the mechanisms underlying the changes in lipid metabolism, by reversing the lipid abnormalities with short-term transdermal and oral ERT. This study is uniquely designed to answer questions about menopausal changes in lipid metabolism, estrogen action and cardiovascular risk in women.