Estrogen, Metabolism, Menopause, and Health Outcomes

雌激素、新陈代谢、更年期和健康结果

• 批准号: 6845085
• 负责人: MARYFRAN R SOWERS
• 金额: $ 41.85万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-15 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6845085
• 关键词: African American; Asian Americans; Hispanic Americans; aging; aromatic hydrocarbon receptor; biological signal transduction; blood lipid; bone density; caucasian American; clinical research; diet; epidemiology; estrogen analog; estrogen receptors; estrogens; hormone regulation /control mechanism; hot flash; human data; longitudinal human study; menopause; menstrual cycle; protein protein interaction; racial /ethnic difference; smoking; steroid hormone metabolism; thrombosis

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.

描述（由申请人提供）：新兴信息表明，雌激素代谢中的差异表达会产生健康结果的差异。族裔群体的观察，尤其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。该应用的目的是评估雌激素代谢产物和异种雌激素的贡献，以及它们的潜在信号通路对过渡到更年期的妇女中选择的后续人类健康措施的潜在信号通路。我们将1）检查吸烟和饮食是否影响雌激素代谢； 2）对雌激素和酚类产物的测定有助于总配体负荷，并确定雌激素对健康状况测度的影响（随访时的绝对水平或基线的绝对水平）因未能说明雌激素模拟物而被错误地归因于3）检查芳基水合碳受体（ARH）与ER受体之间的相互作用，以确定这种相互作用是否改变了雌激素与随后的健康状况测量的缔合（随访时的绝对水平或从基线开始变化）；和4）使用卵泡和黄体相样品，在整个绝经中纵向收集，以确定随着时间的推移，月经周期段中的相对激素差异是否与健康结果有关。待评估的健康状况的度量包括血管舒适症状（热闪光），更年期的年龄，脂质和血栓形成量和骨矿物质密度。该应用程序将在中年进行非裔美国人，高加索人，中国，西班牙裔和日本妇女的现有大型研究中使用储存库血清和尿液样本[全国妇女健康研究（SWAN）]。此外，天鹅可以提供有关吸烟和饮食暴露和健康成果措施的纵向数据，而无需进行其他数据收集。这是一个独特的机会，可以将生活方式元素与激素代谢途径的度量融入对多种人类健康效应的全面检查。