A Longitudinal Study of Endocrine Disruptor Mixtures and Reproductive Aging

项目总结/摘要 暴露于内分泌干扰化学品（EDCs）是广泛的，这些化合物可以持续存在， 环境和人体几十年来。人口正在老龄化，尤其是女性， 随着年龄的增长，会出现严重的发病率和生活质量下降。最近的流行病学数据表明 生殖衰老的时间（卵巢功能随着年龄的增长而逐渐下降）和 绝经过渡期的激素变化影响妇女患慢性病的风险， 健康与衰老虽然许多研究已经审查了对生殖健康的不利影响， 暴露于内分泌干扰物，很少有人知道内分泌干扰物如何影响生殖老化的时间或过程。此外，本发明还 关于这一主题的大多数现有流行病学研究都是对绝经年龄的横断面研究 基于回忆限制因果推理此外，各种内分泌干扰物和污染物的组合暴露- 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，如果在 都写好了这项在多种族女性队列中进行的新流行病学研究旨在更好地 了解内分泌干扰物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 阻燃剂和全氟化合物）和生殖老化的时间，包括年龄 绝经和绝经过渡期的持续时间; 2）评估EDC暴露与 和激素的特点，包括水平和模式的变化， 雌二醇、促卵泡激素、睾酮、性激素结合球蛋白和抗苗勒管激素; 和3）检查多种内分泌干扰物及其相互作用（混合效应）对这些 使用高维协变量（多污染物）回归方法的生殖老化结果 方法）。我们还将探讨种族/民族和EDC的时间变化对效应的影响。我们 将利用15年多来收集的大量表型数据和生物标本， 一个大型的纵向女性队列，全国女性健康研究（n=1,800， 约14，000次观察）。该项目涉及国家环境研究所的战略优先事项， 健康科学，包括综合环境暴露引起的疾病发病机制，以及 环境卫生差距。我们将使用创新的分析方法来解决这些问题， 对污染混合物和人类健康的研究产生新的见解。从中获得的知识 研究可以指导疾病预防措施;随着年龄的增长，提高妇女的健康和福祉; 减少环境卫生差距。

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.