The relationship between urinary phthalate metabolites and polycystic ovary syndrome in women undergoing in vitro fertilization: Nested case-control study.

Certain endocrine disruptor chemicals are involved in the pathogenesis of polycystic ovary syndrome (PCOS), a hormonal disease related to infertility in women. Phthalates are the most common plasticizers found in several consumer products. Experimental and epidemiologic evidence suggests that some phthalates disrupt endocrine functions in reproductive mechanisms and development. We previously measured the levels of eight phthalate metabolites in the urine of 599 Saudi women who underwent in vitro fertilization (IVF) treatment and were enrolled in a prospective study (2015-2017). The current nested case-control study aimed to determine the association between urinary levels of phthalate metabolites and PCOS. Overall, 441 women from the IVF study were identified as eligible for this study. Women in the case group included those diagnosed with PCOS (N = 82). The control group comprised those unable to conceive due to male azoospermia or who underwent preimplantation genetic diagnosis (N = 359). Most urinary phthalate metabolite levels were several-fold higher than those reported in national surveys from other countries. The ratio of luteinizing hormone to follicle-stimulating hormone, an index of PCOS, was significantly higher in the case than in the control group, with no indication of its association with phthalate metabolites. The logistic regression model was applied after adjusting for confounders to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each metabolite modeled as a natural logarithm (ln). For each ln-unit increase in the sum of the four di (2-ethylhexyl) phthalate (∑DEHP) metabolites as well as two individual metabolites, mono-(2-ethyl-5-oxohexyl) phthalate and mono-(2-ethyl-5-carboxypentyl) phthalate, the odds of PCOS increased by 40.5% [OR = 1.405 (95% CI: 1.025, 1.925)], 41.1% [OR = 1.055 (95% CI: 1.055, 1.885)], and 38.6% [OR = 1.386 (95% CI: 1.033, 1.86)], respectively. In contrast, the % odds of PCOS decreased marginally significantly by 44% [OR = 0.560 (95% CI: 0.313, 1.002)] with an ln-unit increase of %MEHP, the ratio of mono-(2-ethylhexyl) phthalate to ∑DEHP. These findings suggest that DEHP may contribute to PCOS, and further investigation is required to understand the underlying mechanisms.