Endocrine disrupting chemicals and risk of uterine fibroids: a prospective study

内分泌干​​扰化学物质与子宫肌瘤的风险：一项前瞻性研究

• 批准号: 9302417
• 负责人: LAUREN A WISE
• 金额: $ 64.33万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9302417
• 关键词: African; African American; Age; Animals; Binding; Biological Markers; Blood; Body mass index; Centers for Disease Control and Prevention (U.S.); Characteristics; Chemical Exposure; Chemicals; Cohort Studies; Communities; Contraceptive Usage; Data; Data Collection; Diagnosis; Endocrine Disruptors; Endocrine system; Environment; Estrogens; Etiology; Exposure to; Fibroid Tumor; Gonadal Steroid Hormones; Gynecologic; Gynecology; Health Care Costs; Health Care Research; High Prevalence; Hormone Receptor; Hormones; Human; Hysterectomy; In Vitro; Incidence; Individual; Infertility; Laboratories; Laboratory Study; Life Style; Link; Location; Measurement; Measures; Menorrhagia; Methodology; Methods; Morbidity - disease rate; National Institute of Child Health and Human Development; National Institute of Environmental Health Sciences; Oral Contraceptives; Participant; Pelvic Pain; Phenols; Policy Maker; Polychlorinated Biphenyls; Population; Pregnancy Complications; Prevalence; Production; Progesterone; Prospective Studies; Prospective cohort study; Questionnaires; Reproductive Process; Research; Research Design; Research Infrastructure; Research Priority; Risk; Risk Factors; Sample Size; Sampling; Serum; Severities; Severity of illness; Sex Behavior; Source; Statistical Data Interpretation; Symptoms; Testing; Time; Training; Ultrasonography; United States; United States National Institutes of Health; Urine; Uterine Fibroids; Woman; Women' s Health; aged; animal data; base; bisphenol A; case control; chemical association; clinically significant; cost; cost effective; design; disorder prevention; epidemiology study; health care quality; high risk population; human data; innovation; parity; phthalates; pollutant; prospective; public health relevance; racial disparity; racial health disparity; reproductive; reproductive hormone; reproductive morbidity; screening; tumor; urinary

 DESCRIPTION (provided by applicant): Uterine leiomyomata (UL) are diagnosed in 25-30% of reproductive-aged women, resulting in considerable gynecologic morbidity and billions in U.S. health care costs annually. African Americans have 2-3 times the UL incidence of Whites and greater disease severity. Sex steroid hormones are involved in the etiology of UL. Given that endocrine disrupting chemicals (EDCs) can alter the functioning of hormones, we propose to evaluate UL risk in relation to 3 classes of EDCs: phthalates, polychlorinated biphenyls (PCBs), and phenols, specifically bisphenol A (BPA). Our choice of chemicals is informed by their high exposure prevalence in humans and by in vitro, animal, and human data documenting their effects on reproductive hormones and processes that could influence UL risk. Existing studies of EDCs and UL are limited by small sample size, uncertain temporality due to retrospective design, and suboptimal measurement of EDCs and UL. This study will use data and biospecimens from the Study of Environment Lifestyle and Fibroids (SELF), a NIEHS prospective cohort study of 1,300 African American women aged 23-34 and free of UL at baseline (2010-2012). Questionnaire data were collected at baseline and subjects are being followed for 5 years. Every 20 months, blood and urine are collected, and ultrasounds are performed by trained sonographers to detect UL. We request support for the laboratory and statistical analysis of EDCs in relation to UL incidence. We propose a cost-effective case-cohort study design that includes 400 incident UL cases and 400 controls. We will measure urinary phthalate metabolites, serum PCBs, and urinary BPA, characterize exposures according to UL risk factors, and determine the associations of these chemicals with UL incidence and tumor characteristics. Non-persistent chemicals (phthalates, BPA) will be measured at baseline, 20 months, and 40 months. Persistent chemicals (PCBs) will be measured at baseline only. SELF provides a unique opportunity to assess the association of common EDCs with UL risk. This project has many strengths that overcome the limitations of prior studies: large sample size, prospective data collection, state-of-the-art EDC measurement, serial ultrasound screening for UL, analysis of repeated EDC measures, innovative statistical approaches for evaluating EDC mixtures, and control for multiple confounders. Pilot data show large exposure variability, providing excellent power to test the proposed hypotheses. This study of African Americans, a high-risk population for EDC exposure and UL, will provide informative data on the effects of widespread pollutants on UL, seek explanations for the racial disparity in UL incidence, and provide critical data to the public, scientific community, and policy makers.