A Longitudinal Study of Endocrine Disruptor Mixtures and Reproductive Aging

项目摘要/摘要 接触内分泌干扰物(EDCs)的情况很普遍，这些化合物可以在体内持续存在 几十年来对环境和人体的影响。人口正在老龄化，尤其是妇女，可以 随着年龄的增长，患者的发病率显著降低，生活质量下降。最近的流行病学数据表明 生殖老化的时间(卵巢功能随年龄逐渐下降)和 绝经过渡期间激素变化影响妇女患慢性病的风险和她们的长期 随年龄增长的长期健康状况。虽然许多研究都检查了对生殖健康的不利影响和 由于暴露在EDCs中，人们对EDCs如何影响生殖衰老的时间或过程知之甚少。此外， 大多数现有的关于这一主题的流行病学研究都是横断面的，对更年期年龄的研究 基于回忆，限制因果推理。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发生 都写好了。这项在多种族女性队列中进行的新的流行病学研究试图更好地 了解EDCs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)之间的关系 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暴露之间的关联 和更年期过渡期间的激素特征，包括水平和变化模式 雌二醇、卵泡刺激素、睾酮、性激素结合球蛋白和抗苗勒氏激素； 3)考察多个内分泌细胞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)回归方法的生殖老化结果 方法)。我们还将探索通过种族/民族和内分泌细胞中的时间变化来改变影响。我们 将利用15年多来收集的大量表型数据和生物标本， 大型纵向妇女队列，全国妇女健康研究(n=1800，总共 ~14,000个观察结果)。该项目涉及国家环境研究所的战略优先事项 健康科学，包括由综合环境暴露引起的疾病发病机制，以及 环境健康差距。我们将使用创新的分析方法来解决这些问题， 为污染混合物和人类健康的研究提供新的见解。从这一过程中获得的知识 研究可以指导疾病预防倡议；提高妇女随着年龄增长的健康和福祉；以及 缩小环境健康差距。

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.