A Longitudinal Study of Endocrine Disruptor Mixtures and Reproductive Aging

内分泌干​​扰物混合物与生殖衰老的纵向研究

• 批准号: 9321364
• 负责人: Sung Kyun Park
• 金额: $ 57.29万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9321364
• 关键词: Address; Affect; Age; Aging; Aging-Related Process; Body Composition; Body Size; Body Weight Changes; Calendar; Characteristics; Chemical Exposure; Chinese People; Chronic Disease; Cohort Studies; Complex; Data; Disease; Dose; Elderly; Endocrine; Endocrine Disruptors; Enrollment; Environment; Environmental Exposure; Environmental Health; Estradiol; Ethnic Origin; Evaluation; Exposure to; Fertility; Flame Retardants; Follicle Stimulating Hormone; Goals; Health; Hispanics; Hormonal; Hormonal Change; Hormones; Human; Human body; Impact evaluation; Individual; Intervention; Japanese Population; Knowledge; Life; Longitudinal Studies; Longitudinal cohort; Measures; Medical; Menopause; Metabolic Diseases; Methods; Mission; Modification; Morbidity - disease rate; National Institute of Environmental Health Sciences; Natural History; Outcome; Ovarian; Pathogenesis; Pattern; Pesticides; Phenotype; Plasticizers; Pollution; Polychlorinated Biphenyls; Population; Postmenopause; Premature Menopause; Premature Mortality; Premenopause; Prospective Studies; Public Health; Quality of life; Race; Reproductive Health; Reproductive Process; Research; Resources; Risk; Risk Factors; Role; Sampling; Scientific Advances and Accomplishments; Serum; Sex Hormone-Binding Globulin; Site; Smoking Status; Specific qualifier value; Specimen; Study of Women' s Health Across the Nation; Subgroup; Testosterone; United States; Variant; Woman; Women' s Health; aged; base; cardiometabolic risk; cigarette smoking; cohort; disorder prevention; environmental chemical; epidemiologic data; epidemiology study; experience; follow-up; health disparity; healthy aging; high dimensionality; innovation; insight; interest; middle age; mortality; mullerian-inhibiting hormone; persistent organic pollutants; phenotypic data; pollutant; pollutant interaction; prevent; prospective; repository; reproductive function; reproductive hormone; reproductive senescence; response; surfactant

Project Summary/Abstract Exposure to endocrine disrupting chemicals (EDCs) is widespread and these compounds can persist in the environment and the human body over decades. The population is aging, and women, in particular, can experience significant morbidity and diminished quality of life with aging. Recent epidemiologic data suggest that the timing of reproductive aging (the gradual decline in ovarian function with age) and the pattern of hormonal change during the menopausal transition influence women’s risk of chronic disease and their long- term health with aging. While numerous studies have examined adverse reproductive health effects and exposure to EDCs, little is known about how EDCs affect the timing or process of reproductive aging. Further, most existing epidemiologic studies on this topic have been cross-sectional with studies of age-at-menopause based on recall, limiting causal inference. In addition, combined exposure to various EDCs and pollutant- pollutant interactions (mixtures), as well as low-dose and non-monotonic dose-responses have been rarely if at all addressed. The proposed new epidemiologic study in a multi-ethnic cohort of women seeks to better understand how EDCs exposure affects the timing and characteristics of reproductive aging. We propose 1) to assess associations between EDC exposure (polychlorinated biphenyls, chlorinated pesticides, brominated flame retardants, and perfluorinated compounds) and timing of reproductive aging, including age at menopause and duration of the menopausal transition; 2) to assess the association between EDC exposure and hormonal characteristics during the menopausal transition, including levels and patterns of change in estradiol, follicle stimulating hormone, testosterone, sex-hormone binding globulin, and anti-Müllerian hormone; and 3) to examine the simultaneous effects of multiple EDCs and their interactions (mixture effects) on these reproductive aging outcomes using regression methods for high-dimensional covariates (multi-pollutant approaches). We will also explore effect modification by race/ethnicity and temporal variations in EDCs. We will capitalize on extensive phenotypic data and biospecimens collected for more than 15 years in an ongoing, large longitudinal cohort of women, the Study of Women’s Health Across the Nation (n=1,800 with a total of ~14,000 observations). This project addresses strategic priorities of the National Institute of Environmental Health Sciences, including disease pathogenesis by combined environmental exposures, as well as environmental health disparities. We will address these issues using innovative analytic approaches likely to yield new insights on the study of pollution mixtures and human health. The knowledge gained from this research may guide disease prevention initiatives; enhance women’s health and wellbeing as they age; and reduce environmental health disparities.

项目摘要/摘要 暴露于内分泌破坏化学物质（EDC）是广泛的，这些化合物可以持续存在 环境和人体数十年。人口正在衰老，尤其是妇女可以 经历大量的发病率和衰老的生活质量降低。最近的流行病学数据表明 生殖衰老的时机（随着年龄的年龄的卵巢功能的年级下降）和 更年期过渡期间的激素变化会影响妇女患慢性疾病的风险及其长期 衰老的任期健康。虽然许多研究检查了不良生殖的健康影响，并且 暴露于EDC，对EDC如何影响生殖衰老的时间或过程知之甚少。更远， 关于该主题的大多数现有流行病学研究都是通过对年龄的研究的研究 根据召回，限制因果推断。另外，对各种EDC和污染物的联合接触 污染物相互作用（混合物）以及低剂量和非单调剂量回答很少是在 所有人都解决了。拟议的一组妇女队列中的新流行病学研究试图更好 了解EDC的暴露如何影响生殖衰老的时间和特征。我们建议1） 评估EDC暴露（多氯联苯，氯化农药，溴化）之间的关联 火焰阻燃剂和全氟化化合物）和生殖衰老的时机，包括年龄 更年期和更年期过渡的持续时间； 2）评估EDC暴露之间的关联 在更年期过渡期间的荷尔蒙特征，包括变化的水平和模式 雌二醇，卵泡刺激马酮，睾丸激素，性激素结合球蛋白和抗肿瘤马龙； 3）检查多个EDC及其相互作用（混合效应）对这些的简单影响 使用回归方法的高维协变量（多污染物）的生殖老化结果 方法）。我们还将探索EDC中种族/种族和临时变化的效果修改。我们 将利用广泛的表型数据和在持续不断的，超过15年的生物测量中 大量的妇女纵向队列，全国妇女健康的研究（n = 1,800，总共 〜14,000观察）。该项目涉及国家环境研究所的战略重点 健康科学，包括通过环境暴露的疾病发病机理以及 环境健康差异。我们将使用可能的创新分析方法来解决这些问题 就污染混合物和人类健康的研究提供新的见解。从中获得的知识 研究可以指导预防疾病计划；随着年龄的增长，增强妇女的健康和福祉；和 减少环境健康分布。