BISPHENOL A LEVELS and ENDOMETRIOSIS RISK IN REPRODUCTIVE-AGE WOMEN

描述（由申请人提供）：本项目的总体目标是在华盛顿州的一项以人群为基础的研究中调查双酚A （BPA）水平与子宫内膜异位症风险之间的关系。BPA是一种用于聚碳酸酯塑料和环氧树脂的聚合物，广泛存在于各种消费品中，包括饮料和食品容器。BPA一直是公众关注和立法行动的焦点，因为这种化学物质迁移到食品和饮料中是人类接触的主要来源，这被认为是慢性和广泛的。虽然双酚a已显示出强烈的雌激素效应，并且在动物研究中与发育和生殖有关的影响水平低于目前人类接触的水平，但关于双酚a对人类健康的影响的信息很少。这项研究将解决这一信息差距，调查成人BPA暴露对一种普遍和严重的女性生殖系统疾病的影响。子宫内膜异位症，子宫外子宫内膜组织的存在，影响了美国大约8-10%的育龄妇女，并与不孕症、严重的慢性盆腔疼痛和痛经有关。子宫内膜异位症是一种雌激素依赖性疾病，激素调节的改变被认为与疾病的发生和发展有关。本研究的中心假设是，在月经周期中暴露于BPA会导致激素反应性子宫内膜组织的结构变化，从而改变组织增殖和破坏的动态调节，从而增加子宫内膜异位症的风险。我们进一步假设，鉴于子宫内膜组织的动态循环变化，从青春期到更年期是暴露于与该疾病相关的双酚a易感性的关键时期。一项基于人群的病例对照研究将在华盛顿州西部一家大型混合模式医疗机构的18-49岁女性参与者中进行，以确定尿液BPA水平与子宫内膜异位症风险之间是否存在关联。次要目的是测试BPA水平与子宫内膜异位症复发之间是否存在关联，以及BPA和强雌激素指标联合暴露是否会影响疾病风险。为了实现这些目标，将对来自“女性子宫内膜异位症风险”研究（V. Holt， PI）的157例患者和298名对照者的存档生物样本进行分析，以确定尿液中总BPA的含量。该研究是一项为期五年的基于人群的子宫内膜异位症病例对照研究，收集了面对面访谈、饮食摄入评估、人体测量、多态基因（GSTM1、COMT）数据和为期两年的辅助研究(V. Holt，PI)收集尿液样本，并测定经血脂调节的血清中有机氯化合物和多氯联苯的水平。所有现有数据将与BPA数据联系起来，以实现具体目标。这项研究的结果解决了我们对这种化学品的安全性认识的严重差距，并将为监管工作提供信息。

DESCRIPTION (provided by applicant): The overall goal of this project is to investigate the relationship between bisphenol A (BPA) levels and the risk of endometriosis in a population-based study of women in Washington State. BPA, a polymer used in polycarbonate plastic and epoxy resin, is present in a wide variety of consumer products, including beverage and food containers. BPA has been the focus of growing public concern and legislative action because migration of the chemical into food and beverages is the primary source of human exposure, which is believed to be chronic and widespread. While BPA has demonstrated strong estrogenic effects and is associated with developmental and reproductive effects in animal studies at levels lower than current human exposures, there is little information concerning the human health effects of BPA. This study will address that information gap, investigating the impact of adult BPA exposure on a prevalent and serious female reproductive-system disease. Endometriosis, the presence of endometrial tissue outside the uterus, affects approximately 8-10% of women of reproductive age in the U.S. and is associated with infertility and severe, chronic pelvic pain and dysmenorrhea. Endometriosis is an estrogen-dependent condition, and alteration in hormonal regulation has been proposed to contribute to disease onset and progression. The central hypothesis in this application is that exposure to BPA 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. We further hypothesize that given the dynamic cyclic changes in endometrial tissue, the years from puberty to menopause are a critical period of susceptibility for exposure to BPA in relation to this disease. A population-based case-control study will be conducted among 18-49 year old female enrollees of a large mixed-model healthcare organization in western Washington State to address the primary Specific Aim: to determine if there is an association between urinary BPA levels and endometriosis risk. The secondary Aims are to test whether there is an association between BPA levels and endometriosis recurrence, and whether disease risk is affected by combined exposure to BPA and strong indicators of estrogenicity. To achieve these Aims, archived biosamples will be analyzed for total urinary BPA among 157 cases and 298 controls from the "Women's Risk of Endometriosis" study (V. Holt, PI), a five-year population-based case-control study of endometriosis that collected in-person interview, dietary intake assessment, anthropometric measurement, polymorphic gene (GSTM1, COMT) data and the two-year ancillary study (V. Holt, PI) that collected urine samples and determined lipid-adjusted serum levels of organochlorine compounds and polychlorinated biphenyls. All existing data will be linked with BPA data to address the Specific Aims. Results of this study address a serious gap in our knowledge of the safety of this chemical, and will inform regulatory efforts. PUBLIC HEALTH RELEVANCE: This is the first U.S. based study to investigate the relationship between adult exposure to the chemical bisphenol A (BPA) and endometriosis, a common female reproductive system disease that causes infertility and pelvic pain. BPA is the focus of current scientific and regulatory concern due both to widespread human exposure and to the association of BPA with developmental and reproductive system effects in animal studies. Because the proposed critical period for exposure to BPA in relation to this disease is during the reproductive years, the findings of this study have the potential for immediate public health impact.