BISPHENOL A LEVELS and ENDOMETRIOSIS RISK IN REPRODUCTIVE-AGE WOMEN

育龄妇女的双酚 A 水平和子宫内膜异位症风险

• 批准号: 8258263
• 负责人: Victoria L Holt
• 金额: $ 8.8万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-15 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8258263
• 关键词: Address; Adult; Affect; Age; Ancillary Study; Animals; Archives; Area; Beverages; Biological; Case-Control Studies; Chemicals; Child; Chlorinated Hydrocarbons; Chronic; Data; Development; Diagnosis; Dietary intake; Dioxins; Disease; Disease Progression; Dose; Dysmenorrhea; Endocrine Disruptors; Endometrial; Environmental Exposure; Epidemiologic Studies; Epoxy Resins; Estrogen Metabolism; Estrogens; Exposure to; Female; Female Reproductive System Disorder; Food; Food Container; Funding; GSTM1 gene; Genetic Polymorphism; Goals; Health; Healthcare; Healthcare Systems; Height; Human; Infertility; Interview; Investigation; Knowledge; Link; Lipids; Measurement; Menopause; Menstrual cycle; Modeling; National Institute of Environmental Health Sciences; Onset of illness; Outcome; Pelvic Pain; Persons; Physical activity; Policies; Polychlorinated Biphenyls; Polymers; Predisposition; Principal Investigator; Puberty; Public Health; Recurrence; Regulation; Reproductive Health; Reproductive system; Research; Risk; Role; Safety; Sales; Sampling; Serum; Site; Source; Sports; Study Subject; Testing; Tissues; United States Food and Drug Administration; United States National Institutes of Health; Urine; Uterus; Washington; Woman; base; bisphenol A; chronic pelvic pain; consumer product; cost; critical period; disorder risk; endometriosis; exposed human population; hormone regulation; implantation; migration; organochlorine pesticide; pollutant; polycarbonate plastic; population based; public health relevance; reproductive; response; urinary

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.

描述（由申请人提供）：该项目的总体目标是在华盛顿州女性的一项基于人群的研究中调查双酚 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，存在于多种消费品中，包括饮料和食品容器。双酚 A 一直是公众日益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双酚 A 的主要来源，而且这种接触被认为是长期且广泛的。虽然 BPA 已表现出强烈的雌激素作用，并且在动物研究中与发育和生殖影响相关，但其水平低于目前人类的暴露水平，但有关 BPA 对人类健康影响的信息很少。这项研究将解决这一信息差距，调查成人接触 BPA 对一种普遍且严重的女性生殖系统疾病的影响。子宫内膜异位症（子宫内膜组织存在于子宫外）影响着美国大约 8-10% 的育龄妇女，并与不孕以及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病症，激素调节的改变被认为有助于疾病的发作和进展。本申请的中心假设是，月经周期期间接触 BPA 会导致激素反应性子宫内膜组织发生结构变化，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。我们进一步假设，考虑到子宫内膜组织的动态周期性变化，从青春期到绝经期是接触 BPA 与这种疾病相关的关键时期。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，以实现主要的具体目标：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。次要目标是测试 BPA 水平与子宫内膜异位症复发之间是否存在关联，以及疾病风险是否受到 BPA 和强雌激素指标的联合暴露的影响。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 例病例和 298 名对照者的已存档生物样本进行总尿 BPA 分析，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、膳食摄入评估、人体测量、多态性基因（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脂质调整后的有机氯化合物和多氯联苯的血清水平。所有现有数据将与 BPA 数据链接以实现特定目标。这项研究的结果解决了我们对该化学品安全性的认识中存在的严重差距，并将为监管工作提供信息。 公共健康相关性：这是第一项美国研究，调查成人接触化学物质双酚 A (BPA) 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系统疾病，会导致不孕和骨盆疼痛。由于人类广泛接触 BPA，以及动物研究中 BPA 与发育和生殖系统影响的关联，BPA 成为当前科学和监管关注的焦点。由于建议的接触 BPA 与该疾病相关的关键时期是在生育年龄，因此这项研究的结果可能对公共健康产生直接影响。