Estrogen, Metabolism, Menopause, and Health Outcomes

描述（由申请人提供）：新出现的信息表明，雌激素代谢的差异表达产生健康结果的差异。来自不同种族群体的观察，特别是亚洲人和高加索人的比较，引起了人们对雌激素代谢和健康状况差异的兴趣和争议。本申请的目的是评估雌激素代谢物和异种雌激素及其潜在信号传导途径对绝经过渡期妇女选定的后续人类健康措施的贡献。我们将1）检查吸烟和饮食是否影响雌激素代谢; 2）测定雌激素和酚类产物，这些产物有助于总配体负荷，并确定雌激素是否影响健康状况的测量（随访时的绝对水平或较基线的变化）由于未能解释雌激素模拟物而被错误归因; 3）检查芳烃受体（ArH）和ER受体之间的相互作用，以确定这种相互作用是否改变雌激素与随后的健康状况测量的关联（随访时的绝对水平或从基线的变化）;和4）使用在绝经过渡期纵向收集的卵泡和黄体期样品，以确定月经周期段中随时间的相对激素差异是否与健康结果相关。待评估的健康状况指标包括血管炎症状（潮热）、绝经年龄、血脂和血栓形成指标以及骨矿物质密度。本申请将使用来自现有大型中年非裔美国人、高加索人、中国人、西班牙裔和日本女性研究[全国女性健康研究（SWAN）]的储存库血清和尿液样本。此外，SWAN可以提供有关吸烟和饮食暴露以及健康结果测量的纵向数据，而无需额外的数据收集。这是一个独特的机会，可以前瞻性地将生活方式元素与激素代谢途径的措施整合到对多种人类健康影响的全面检查中。

DESCRIPTION (provided by applicant): Emerging information suggests that differential expression in estrogen metabolism generates differences in health outcomes. Observations from ethnic groups, particularly comparisons of Asians and Caucasians, have precipitated both interest and controversy about differences in estrogen metabolism and health status. The goal of this application is to assess the contribution of estrogen metabolites and xenoestrogens as well as their potential signaling pathways to selected subsequent human health measures in women transitioning the menopause. We will 1) examine whether smoking and diet influence estrogen metabolism; 2) assay for both estrogens and phenolic products that contribute to the total ligand load and determine if estrogen effects on measures of health status (absolute level at follow-up or change from baseline) are misattributed because of failure to account for estrogen mimics; 3) examine the interaction between the arylhydrocarbon receptor (ArH) and ER receptors to ascertain if this interaction modifies the association of estrogens to subsequent measures of health status (absolute level at follow-up or change from baseline); and 4) use follicular and luteal phase samples, collected longitudinally across the menopausal transition, to ascertain if the relative hormone differences in the menstrual cycle segments over time are related to health outcomes. The measures of health status to be evaluated include vasomotor symptoms (hot flashes), age at menopause, measures of lipids and thrombosis and bone mineral density. This application will use Repository serum and urine samples from an existing large study of African-American, Caucasian, Chinese, Hispanic and Japanese women at the midlife [Study of Women's Health Across the Nation (SWAN)]. Additionally, SWAN can provide the longitudinal data about both smoking and diet exposures and health outcomes measures without additional data collection. This is a unique opportunity to prospectively integrate lifestyle elements with measures of hormone metabolism pathways into a comprehensive examination of multiple human health effects.