Phthalates and risk of endometriosis

Abstract

Background: Phthalates are ubiquitous environmental chemicals with endocrine disruptive properties. The impact of these chemicals on endocrine-related disease in reproductive-age women is not well understood.

Objective: To investigate the relationship between urinary phthalate metabolite concentrations and the risk of a hormonally-driven disease, endometriosis, in reproductive-age women.

Methods: We used data from a population-based case-control study of endometriosis, conducted among female enrollees of a large healthcare system in the U.S. Pacific Northwest. We measured urinary phthalate metabolite concentrations on incident, surgically-confirmed cases (n=92) diagnosed between 1996 and 2001 and population-based controls (n=195). Odds ratios (OR), and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for urinary creatinine concentrations, age, and reference year.

Results: The majority of women in our study had detectable concentrations of phthalate metabolites. We observed a strong inverse association between urinary mono-(2-ethyl-5-hexyl) phthalate (MEHP) concentration and endometriosis risk, particularly when comparing the fourth and first MEHP quartiles (aOR 0.3, 95% CI: 0.1-0.7). Our data suggested an inverse association between endometriosis and urinary concentrations of other di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)) and ∑DEHP, however, the confidence intervals include the null. Our data also suggested increased endometriosis risk with greater urinary concentrations of mono-benzyl phthalate (MBzP) and mono-ethyl phthalate (MEP), although the associations were not statistically significant.

Conclusions: Exposure to select phthalates is ubiquitous among female enrollees of a large healthcare system in the U.S. Pacific Northwest. The findings from our study suggest that phthalates may alter the risk of a hormonally-mediated disease among reproductive-age women.

Keywords: BMI; BzBP; CI; DAG; DBP; DEHP; DEP; Endometriosis; Environmental health; Epidemiology; GH; GM; Group Health; LOQ; MBzP; MECPP; MEHHP; MEHP; MEOHP; MEP; MiBP; MnBP; NHANES; National Health and Nutrition and Evaluation Survey; OR; POPs; Persistent Organic Pollutants and endometriosis risk study; Phthalate; Population-based case-control study; WREN; Women's Risk of Endometriosis study; benzyl butyl phthalate; body mass index; confidence interval; di-(2-ethylhexyl) phthalate; dibutyl phthalate; diethyl phthalate; directed acyclic graph; geometric mean; limit of quantitation; mono-(2-ethyl-5-carboxypentyl) phthalate; mono-(2-ethyl-5-hexyl) phthalate; mono-(2-ethyl-5-hydroxyhexyl) phthalate; mono-(2-ethyl-5-oxohexyl) phthalate; mono-benzyl phthalate; mono-ethyl phthalate; mono-iso-butyl phthalate; mono-n-butyl phthalate; odds ratio.