Organochlorine pesticides, phthalate metabolites, and risk of endometriosis

Abstract

Background: Endometriosis is an estrogen-driven benign gynecologic condition that may be affected by exposure to environmental chemicals that mimic or alter endogenous hormonal activity, such as organochlorine pesticides (OCPs) and phthalates. However, the impact of these chemicals on endometriosis risk remains unclear, as prior epidemiologic studies have had conflicting results. Additionally, basic information is lacking on characteristics associated with increased phthalate body burden among premenopausal women. Methods: This research investigated the relationships between OCPs, phthalate metabolites, and endometriosis risk and predictors of phthalate exposure using data from a population-based case-control study of endometriosis, Women's Risk of Endometriosis (WREN). WREN was conducted among 18-49 year old female enrollees of a large healthcare system in the U.S. Pacific Northwest. OCP concentrations were measured in the serum of 248 cases and 538 controls and urinary phthalate metabolites were quantified on 92 cases and 195 controls. To investigate the relationship between environmental chemicals and endometriosis risk, odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression. To examine predictors of phthalate exposure, ratios of median phthalate metabolite concentrations and 95% CI were estimated using linear regression. Results: Serum concentrations of β-hexachlorocyclohexane, particularly in analyses restricting cases to those with ovarian endometriosis, and mirex were associated with increased endometriosis risk. A strong inverse association was observed between urinary mono-(2-ethyl-5-hexyl) phthalate (MEHP) concentration and endometriosis risk. The data suggested an inverse association with other di-2-ethylhexyl phthalate (DEHP) metabolites and a positive association with mono-benzyl phthalate (MBzP) and mono-ethyl phthalate (MEP). Mono-isobutyl phthalate (MiBP) concentrations were inversely associated with waist circumference and waist-to-hip ratio. Trends across hours of the day (summed metabolites of DEHP), days of the week (MEP), and seasons of the year (MiBP) were observed. Conclusions: This research suggests that environmental exposure to OCPs and phthalates may alter endometriosis risk and that subgroups of premenopausal women may have increased phthalate exposure. Nearly ubiquitous exposure to phthalates as well as extensive past use of environmentally persistent OCPs in the United States or present use in other countries may impact the current health of reproductive-age women.