Estrogen, Metabolism, Menopause, and Health Outcomes

描述（由申请人提供）：新发现的信息表明，雌激素代谢的差异表达会导致健康结果的差异。来自不同种族的观察，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。本应用程序的目的是评估雌激素代谢物和异种雌激素及其潜在的信号通路对绝经妇女选择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)测定对总配体负荷有贡献的雌激素和酚类产物，并确定雌激素对健康状况测量（随访时的绝对水平或基线变化）的影响是否因未能解释雌激素模拟物而被错误归因于；3)检查芳烃受体（ArH）和内质网受体之间的相互作用，以确定这种相互作用是否会改变雌激素与随后健康状况测量的关联（随访时的绝对水平或从基线开始的变化）；4)利用在绝经过渡期纵向收集的卵泡期和黄体期样本，确定月经周期各阶段的相对激素差异是否与健康结果有关。需要评估的健康状况指标包括血管舒缩症状（潮热）、绝经年龄、血脂、血栓形成和骨密度。该应用程序将使用数据库中的血清和尿液样本，这些样本来自一项现有的针对非裔美国人、高加索人、中国人、西班牙裔和日本中年妇女的大型研究[全国妇女健康研究（SWAN）]。此外，SWAN可以提供关于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因素与激素代谢途径的测量结合起来，对多种人类健康影响进行全面检查。

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.