Urinary monoester phthalate metabolites and thyroid function in healthy adults: Sex- and obesity-specific associations.

Abstract

Phthalates are widespread endocrine-disrupting chemicals that may subtly alter thyroid homeostasis, although the influence of sex and adiposity on these associations remains unclear. This cross-sectional study investigated the associations of urinary monoethyl phthalate (MEP) and mono(2-ethylhexyl) phthalate (MEHP) with thyroid function according to sex and body mass index (BMI). The study included 201 metabolically healthy adults aged 18-57 years from Serbia. First-morning urine samples were analyzed for phthalate metabolites by gas chromatography-mass spectrometry, while serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured using a chemiluminescent immunoassay. Participants were classified as lean or overweight and obese, and associations were evaluated using group comparisons and hierarchical multiple linear regression. MEP and MEHP concentrations were above the limit of quantification (LOQ) in 31.84% and 21.89% of samples, respectively. Overweight and obese participants with MEP concentrations above the LOQ had higher FT4 levels than those with concentrations below the LOQ, whereas lean participants with MEHP above the LOQ had lower FT4 levels. Regression analyses identified a significant interaction among MEP, BMI, and sex for TSH, with higher MEP associated with higher TSH primarily in overweight and obese women. A significant interaction among MEHP, BMI, and sex was also observed for FT3, although the inverse association in lean men was only marginally significant. Urinary MEP and MEHP were associated with subtle, sex- and adiposity-dependent variations in thyroid hormone levels within physiological ranges. These exploratory findings require confirmation in larger longitudinal studies using repeated exposure measurements.