Endogenous/Exogenous Sex Hormones & CHD Risk Factors

描述（由申请人提供）： 冠心病（CHD）是美国女性最常见的死亡原因。 观察性研究一致表明，绝经后雌激素，或 不含孕激素，可降低冠心病的风险，并且有几种可能 雌激素保护心脏的机制。尽管如此，临床 迄今为止的试验尚未证明其具有心脏保护作用。如果激素水平发挥作用 在确定绝经后妇女的冠心病风险中发挥作用，并且将使用激素替代疗法 作为降低风险的一种手段，内源性激素的相互作用， HRT 和冠心病风险因素需要进一步定义，特别是 协变量。个体特征，例如基础激素水平、身体 体型、过去使用激素和生活方式的决定可能会改变对 HRT 的反应。 该提案主要关注四个问题：1）哪些因素决定流通 绝经后女性性激素水平，2) 哪些因素决定变化 性激素水平对激素替代疗法 (HRT) 的反应，3) 内源性激素水平影响绝经后冠心病危险因素 女性，4) 激素替代疗法（HRT）引起的性激素水平变化是否可以预测 HRT 对 CHD 危险因素的影响。这些问题将通过分析来解答 绝经后雌激素/孕激素干预试验的现有数据 (PEPI)，一项为期 3 年、多中心、双盲、安慰剂对照试验 旨在比较单独使用雌激素和 3 种雌激素/孕激素 HRT 的效果 治疗方案与安慰剂对选定的冠心病危险因素的比较。共有 875 名参与者。 血清性激素水平、CHD 危险因素和潜在协变量 （包括人口统计特征、人体测量数据、 生殖史和生活方式变量），在基线和在 分析中将考虑 24 或 36 个月的治疗。结果 这项研究将有助于确定女性之间在以下方面的差异 内源性激素水平和对 HRT 的反应以及性别的关系 激素对冠心病危险因素的影响。这些观察可能有助于决定是否 个别女性应该使用 HRT，如果是的话，哪种方案可以提供 以最小的风险获得最大的收益。

DESCRIPTION (provided by applicant): Coronary heart disease (CHD) is the most common cause of death in U.S. women. Observational studies consistently show that postmenopausal estrogen, with or without a progestin, reduces the risk of CHD, and there are several plausible mechanisms by which estrogen might protect the heart. Nevertheless, clinical trials to date have not demonstrated cardioprotection. If hormone levels play a role in determining CHD risk in postmenopausal women and HRT is to be used as a means of reducing that risk, the interactions of endogenous hormones, HRT, and CHD risk factors need further definition, in particular the effect of covariates. Individual characteristics such as basal hormone levels, body size, past hormone use, and lifestyle decisions may modify responses to HRT. This proposal focuses on four questions: 1) what factors determine circulating sex hormone levels in postmenopausal women, 2) what factors determine changes in sex hormone levels in response to hormone replacement therapy (HRT), 3) do endogenous sex hormone levels influence CHD risk factors in postmenopausal women, and 4) do changes in sex hormone levels with HRT predict the effect of HRT on CHD risk factors. These questions will be addressed by analyzing existing data from the Postmenopausal Estrogen / Progestin Interventions Trial (PEPI), a 3-year, multi-center, double-blind, placebo-controlled trial designed to compare the effect of estrogen alone and 3 estrogen/progestin HRT regimens vs placebo on selected CHD risk factors. There were 875 participants. Serum sex hormone levels, CHD risk factors, and potential covariates (including demographic characteristics, anthropometric measurements, reproductive history and lifestyle variables), determined at baseline and at 24 or 36 months of treatment, will be considered in the analyses. Results of this study will help define the differences between women with regard to endogenous sex hormone levels and responses to HRT, and the relation of sex hormones to CHD risk factors. These observations may aid in deciding whether individual women should use HRT and, if so, which regimen would provide the most benefit with the least risk.