Effects of Endocrine Disruptors on Endometriosis Risk in Reproductive Age Women

描述(申请人提供)：这项研究的总体目标是调查内分泌干扰物(EDCs)，特别是选择邻苯二甲酸酯和持久性有机氯农药(OCP)与育龄妇女子宫内膜异位症风险的关系。人们越来越担心邻苯二甲酸酯的安全性，邻苯二甲酸酯是一种人造化学品，用于制造包括塑料和个人护理产品在内的许多家用物品。在美国人群中几乎无处不在地检测到几种邻苯二甲酸盐代谢物，表明存在广泛的接触。同样令人担忧的是，有机氯农药是尽管在过去几十年里被禁止或限制使用，但仍在环境中持续存在的杀虫剂。邻苯二甲酸酯和有机氯农药都是模拟或改变内源性激素活性的内分泌细胞，然而，关于这些内分泌细胞对成人健康的潜在影响的数据很少。这项研究将通过调查成人接触邻苯二甲酸盐和有机氯农药对流行的女性生殖状况的影响来解决这一知识差距。子宫内膜异位症的特征是子宫内膜组织植入子宫外，在美国大约有8%-10%的育龄妇女受到影响，并与严重的盆腔疼痛和不孕症有关。这项研究的中心假设是，在月经周期中暴露于邻苯二甲酸盐或有机氯农药会导致对激素敏感的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，一项基于人群的病例对照研究将在华盛顿州一个大型混合模式医疗保健系统的参与者中进行，研究对象为18-49岁的女性，使用存档的生物样本和“女性子宫内膜异位症的复发风险研究和继续研究”(R01 HD33792)和“持久性有机污染物与子宫内膜异位症风险”辅助研究(EPA授予No。R829438)。这项研究将分析135例患者和165名对照的存档尿样中邻苯二甲酸盐代谢物的水平，并将使用之前分析251例患者和538名对照的OCPs的血清数据，与现有研究数据的丰富联系起来，以解决主要目的：测试子宫内膜异位症的风险是否与尿中8种邻苯二甲酸酯代谢物的水平有关，测试子宫内膜异位症的风险是否与血清14种OCPs水平或自我报告OCP暴露有关，并找出与对照组中尿邻苯二甲酸代谢物水平上四分位或血清OCP水平相关的预测因素。第二个目的是检验子宫内膜异位症复发的风险是否与8个尿邻苯二甲酸盐代谢物水平或14个OCPs的血清水平有关，并检验14个OCPs的血清水平与对照组中14个OCPs暴露的自我报告之间的相关性。这项拟议的项目将为国家护理研究所整合生物学和行为学以促进科学发展的研究计划做出重要贡献。这项研究的结果将解决关于邻苯二甲酸盐和有机氯农药对人类健康的潜在不利影响的知识差距。

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.