Exposure to Endocrine Disrupting Compounds and Reproductive Toxicity in Women

The overall objective of the research presented in this dissertation was to assess exposure to endocrine disrupting chemicals (EDCs), polychlorinated biphenyls (PCBs), phthalates, and bisphenol A (BPA) in the general population and evaluate their associations with adverse reproductive health effects, including cancers, in women. Given the proven contribution of unopposed estrogens to the risk for endometrial neoplasia or breast cancer, renewed health concerns have aroused about estrogen mimicking EDCs found in food, personal care products or as environmental contaminants. Our meta-analysis showed that exposure to estrogen mimicking PCBs increased summary risk of breast cancer and endometriosis. We further evaluated the relationship between endometriosis and breast cancer, and EDCs using a bioinformatics method. Our bioinformatics approach was able to identify genes with the potential to be involved in interaction with PCB, phthalates and BPA that may be important to the development of breast cancer and endometriosis. Therefore, we hypothesized that exposure to EDCs such as PCBs, phthalates, and BPA, results in adverse reproductive health effects in women. Using subject data and biomarkers available from the Center for Disease Controls National Health and Nutrition Examination Survey database we conducted a cross-sectional study of EDCs in relation to self-reported history of endometriosis, uterine leiomyomas, breast cancer, cervical cancer, ovarian cancer, and uterine cancer. Significantly higher body burdens of PCBs were found in women diagnosed with breast cancer, ovarian cancer, and uterine cancer compared to women without cancer. PCB 138 was significantly associated with breast cancer, cervical cancer, and uterine cancer, while PCBs 74 and 118 were significantly associated with ovarian cancer. The sum of dioxin-like PCBs were significantly associated with ovarian cancer (OR of 2.02, 95% CI: 1.06-3.85) and the sum of non-dioxin-like PCBs were significantly associated with uterine cancer (OR of 1.12, 95%CI: 1.03-1.23). Significantly higher body burdens of PCBs were also found in women diagnosed with endometriosis and uterine leiomyomas. Documenting the exposure to EDCs among the general U.S. population, and identifying agents associated with reproductive toxicity have the potential to fill research gaps and facilitate our understanding of the complex role environmental chemicals play in producing toxicity in reproductive organs.