ESTROGENS, BODY FAT AND DYSLIPIDEMIA AT MENOPAUSE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在发达国家，冠心病(CHD)是女性死亡的主要原因，绝经似乎会导致CHD风险的加速。这项研究的目的是进一步描述绝经后脂代谢的变化，并探讨这些脂变化的机制。中年胆固醇研究是一项前瞻性的纵向研究(n=120)，旨在调查1)雌激素缺乏(观察组)和2)雌激素替代疗法(ERT)(干预组)对脂代谢的影响。仍处于绝经前的女性将作为对照对象，使我们能够区分衰老和雌激素缺乏对脂肪代谢的影响。在介入组中，从绝经前过渡到绝经后的妇女(n=48)被随机分成一项交叉研究，比较短期口服和透皮雌激素对脂代谢的影响。我们将1)确定脂代谢蛋白(CETP和PLTP)和雄激素在绝经后出现致动脉粥样硬化脂质谱中的作用，2)确定绝经后是否导致高密度脂蛋白颗粒亚类谱的致动脉粥样硬化转变，以及3)评估中枢脂肪积累对绝经后胰岛素敏感性变化的影响。此外，介入臂将使我们能够通过短期经皮和口服ERT逆转脂质异常，从而证实脂代谢变化的机制。这项研究是专门为回答有关更年期妇女脂代谢变化、雌激素作用和心血管风险的问题而设计的。

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.