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

基本信息

批准号：
10088443
负责人：
Sung Kyun Park
金额：
$ 26.51万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10088443
关键词：
Address Affect Age Aging Body Composition Body Size Body Weight Changes Calendar Cardiometabolic Disease Characteristics Chemical Exposure Chinese People Chronic Disease Cohort Studies Complex Data Disease Dose Endocrine Endocrine Disruptors Enrollment Environment Environmental Exposure 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 Longterm Follow-up Measures Medical Menopause Methods Mission Modification Morbidity - disease rate National Institute of Environmental Health Sciences Natural History Outcome Ovarian Pathogenesis Pattern Personal Satisfaction Pesticides Phenotype Plasticizers Pollution Polychlorinated Biphenyls Population Postmenopause Premature Menopause Premature Mortality Premenopause Process 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&apos s Health Across the Nation Subgroup Testosterone United States Variant Woman Women&apos s Health aged base cigarette smoking cohort disorder prevention environmental chemical environmental health disparity epidemiologic data epidemiology study experience healthy aging high dimensionality human old age (65+)innovation insight interest middle age mortality mortality risk mullerian-inhibiting hormone multi-ethnic persistent organic pollutants phenotypic data pollutant pollutant interaction prevent prospective repository reproductive function reproductive hormone reproductive senescence response sociodemographic factors surfactant

项目摘要

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.

项目概要/摘要内分泌干扰化学物质 (EDC) 的接触非常普遍，这些化合物可能会持续存在于体内几十年来，人口正在老龄化，尤其是女性。最近的流行病学数据表明，随着年龄的增长，人们的发病率和生活质量都会下降。生殖衰老的时间（卵巢功能随着年龄的增长而逐渐衰退）和模式更年期过渡期间荷尔蒙的变化影响女性患慢性病的风险及其长期虽然许多研究已经研究了对生殖健康的不利影响和接触 EDC 后，人们对 EDC 如何影响生殖衰老的时间或过程知之甚少。关于这一主题的大多数现有流行病学研究都是针对绝经年龄的横断面研究基于召回，限制因果推断此外，综合暴露于各种 EDC 和污染物。污染物相互作用（混合物）以及低剂量和非单调剂量反应很少见拟议的针对多种族女性队列的新流行病学研究旨在更好地解决这些问题。了解 EDC 暴露如何影响生殖衰老的时间和特征我们建议 1) 评估了 EDC 暴露（多氯联苯、氯化农药、溴化农药）之间的关联阻燃剂和全氟化合物）和生殖衰老的时间，包括年龄 2) 评估EDC暴露之间的关联和绝经过渡期间的荷尔蒙特征，包括变化的水平和模式雌二醇、卵泡刺激素、睾酮、性激素结合球蛋白和抗苗勒氏管激素； 3) 检查多种 EDC 的同时效应及其相互作用（混合效应）使用高维协变量（多污染物我们还将探讨 EDC 中种族/民族和时间变化的影响。将利用超过 15 年收集的广泛表型数据和生物样本，持续、全国女性健康研究（n=1,800，总共约 14,000 条观察结果）。该项目涉及国家环境研究所的战略重点。健康科学，包括综合环境暴露造成的疾病发病机制，以及我们将使用可能的创新分析方法来解决这些问题。从中获得的知识对污染混合物和人类健康的研究产生了新的见解。研究可以指导疾病预防举措；增强女性的健康和福祉；以及减少环境健康差异。