Effects of Endocrine Disruptors on Endometriosis Risk in Reproductive Age Women

内分泌干​​扰物对育龄妇女子宫内膜异位症风险的影响

• 批准号: 8196531
• 负责人: Kristen Upson
• 金额: $ 3.54万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2013-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8196531
• 关键词: Address; Adult; Adverse effects; Affect; Age; Ancillary Study; Animals; Archives; Behavior; Biology; Case-Control Studies; Chemicals; Child; Chronic; Complex; Data; Detection; Dioxins; Disease; Endocrine; Endocrine Disruptors; Endocrine disruption; Endometrial; Environment; Estrogens; Etiology; Exhibits; Exposure to; Female; Functional disorder; Funding; Genetic; Goals; Grant; Growth; Health; Healthcare Systems; Hormones; Household; Human; In Vitro; Infertility; Intervention; Interview; Knowledge; Link; Measures; Mediating; Medical Records; Menstrual cycle; Modeling; National Institute of Nursing Research; Patient Self-Report; Pelvic Pain; Pesticides; Pharmacy facility; Plastics; Policies; Polychlorinated Biphenyls; Population; Principal Investigator; Public Health; Recurrence; Regulation; Research; Research Project Grants; Risk; Safety; Sampling; Science; Self Care; Serum; Solvents; Specimen; Study Subject; Testing; Tissues; United States National Institutes of Health; Urine; Uterus; Washington; Woman; child bearing; chronic pelvic pain; design; endometriosis; environmental chemical; estrogenic activity; implantation; improved; man; men; organochlorine pesticide; organochlorine pesticide exposure; phthalates; pollutant; population based; programs; reproductive; urinary

DESCRIPTION (provided by applicant): The overall goal of this study is to investigate the relationship between endocrine disrupting chemicals (EDCs), specifically select phthalates and persistent organochlorine pesticides (OCPs), and risk of endometriosis in reproductive-age women. There is emerging concern about the safety of phthalates, man-made chemicals used in the manufacturing of many household items including plastics and personal care products. Nearly ubiquitous detection of several phthalate metabolites in the US population suggests widespread exposure. Similarly concerning, OCPs are pesticides that continue to persist in the environment despite being banned or restricted in use over the past several decades. Both phthalates and OCPs are EDCs that mimic or alter endogenous hormone activity, however, little data exists about the potential adult human health effects posed by these EDCs. This study will address this gap in knowledge by investigating the impact of adult exposure to phthalates and OCPs in relation to a prevalent female reproductive condition. Endometriosis, characterized by the implantation of endometrial tissue outside the uterus, affects approximately 8-10% of reproductive age women in the US and is associated with severe pelvic pain and infertility. The central hypothesis in this study is that exposure to phthalates or OCPs during the menstrual cycle results in structural changes in hormonally- responsive endometrial tissue that alter the dynamic regulation of tissue proliferation and breakdown and thus increase the risk of endometriosis. To test this hypothesis, a population-based case-control study will be conducted among women ages 18-49 who are enrollees of a large, mixed-model health care system in Washington State using archived biosamples and data collected in the "Women's Risk of Endometriosis" study and continuation study of recurrence (R01 HD33792) and the "Persistent Organic Pollutants and Endometriosis Risk" ancillary study (EPA grant no. R829438). The study will analyze archived urine specimens from 135 cases and 165 controls for phthalate metabolite levels and will use data from serum previously analyzed for OCPs among 251 cases and 538 controls linked to the wealth of existing study data to address the primary aims: to test whether the risk of endometriosis is associated with urinary levels of 8 phthalate metabolites, to test whether the risk of endometriosis is associated with serum levels of 14 OCPs, or self-report of OCP exposure, and to identify predictors associated with the upper quartile of urinary phthalate metabolite levels, or serum OCP levels, among controls. The secondary aims are to test whether the risk of endometriosis recurrence is associated with 8 urinary phthalate metabolite levels, or serum levels to 14 OCPs and to examine the correlation between serum levels of 14 OCPs and self-report of exposure to 14 OCPs among controls. The proposed project will make an important contribution to the National Institute of Nursing Research's research program to integrate biology and behavior to advance science. The results of this study will address the gap in knowledge about the potential adverse effects of phthalates and OCPs on human health. PUBLIC HEALTH RELEVANCE: This study investigates the relationship between adult exposure to phthalates and organochlorine pesticides in relation to endometriosis, a common female reproductive condition that is associated with infertility and chronic pelvic pain. The findings of this study have the potential for considerable public health importance given the widespread exposure of the US population to phthalates, the environmental persistence of organochlorine pesticides, and the adverse reproductive effects exhibited by these chemicals in female animal studies.

描述（由申请人提供）：本研究的总体目标是调查内分泌干扰化学品（EDCs），特别是选择邻苯二甲酸酯和持久性有机氯农药（OCPs）与育龄妇女子宫内膜异位症风险之间的关系。人们对邻苯二甲酸盐的安全性越来越感到担忧，邻苯二甲酸盐是一种人造化学品，用于制造许多家庭用品，包括塑料和个人护理产品。在美国人群中几乎普遍检测到几种邻苯二甲酸酯代谢物，表明广泛暴露。同样令人担忧的是，尽管在过去几十年中被禁止或限制使用，但有机氯农药仍然存在于环境中。邻苯二甲酸酯和OCP都是模拟或改变内源性激素活性的内分泌干扰物，然而，关于这些内分泌干扰物对成人健康的潜在影响的数据很少。本研究将通过调查成人暴露于邻苯二甲酸酯和OCP对普遍女性生殖状况的影响来解决这一知识缺口。子宫内膜异位症的特征是子宫内膜组织植入子宫外，影响美国约8-10%的育龄妇女，并与严重的盆腔疼痛和不孕症有关。本研究的中心假设是，在月经周期期间暴露于邻苯二甲酸酯或OCP会导致子宫内膜组织的结构变化，从而改变组织增殖和分解的动态调节，从而增加子宫内膜异位症的风险。为了验证这一假设，将在18-49岁的女性中进行一项基于人群的病例对照研究，华盛顿州的混合模式卫生保健系统，使用存档的生物样本和“妇女子宫内膜异位症风险”研究和复发的持续研究中收集的数据（R 01 HD 33792）和“持久性有机污染物和子宫内膜异位症风险”辅助研究（EPA批准号R829438）。本研究将分析来自135例病例和165例对照的存档尿液标本的邻苯二甲酸酯代谢物水平，并将使用先前分析的251例病例和538例对照血清中OCP的数据，这些数据与丰富的现有研究数据相关，以解决主要目的：为了测试子宫内膜异位症的风险是否与8种邻苯二甲酸酯代谢物的尿水平相关，检测子宫内膜异位症的风险是否与14种OCP的血清水平或OCP暴露的自我报告相关，并确定与对照组中尿邻苯二甲酸酯代谢物水平或血清OCP水平的上四分位数相关的预测因子。次要目的是测试子宫内膜异位症复发的风险是否与8种尿邻苯二甲酸酯代谢物水平或14种OCP的血清水平相关，并检查14种OCP的血清水平与对照组中14种OCP暴露的自我报告之间的相关性。该项目将为国家护理研究所的研究计划做出重要贡献，以整合生物学和行为学来推进科学。本研究的结果将解决邻苯二甲酸酯和OCP对人类健康潜在不良影响的知识差距差距。 公共卫生关系：本研究调查了成人暴露于邻苯二甲酸酯和有机氯农药与子宫内膜异位症之间的关系，子宫内膜异位症是一种常见的女性生殖疾病，与不孕症和慢性盆腔疼痛有关。鉴于美国人口广泛接触邻苯二甲酸酯、有机氯农药的环境持久性以及这些化学物质在雌性动物研究中表现出的不良生殖影响，本研究的结果可能具有相当大的公共卫生重要性。