Endocrine Abstracts

Background: Perfluoroalkyl substances (PFAS) are endocrine disrupting chemicals, with elimination half-lives ranging from four to eight years. Experimental studies indicate that PFAS may disrupt androgenic and estrogenic pathways, potentially affecting fetal development. During 1st trimester, concentrations of sex hormone-binding globulin (SHBG) increase due to higher estrogen levels from the placenta. The increment of SHBG concentration results in a compensatory increase in total testosterone (TT) in women at 1st and 2nd trimester, but levels of free testosterone (Free-T) remain within the range of non-pregnant women. Circulating Free-T increases significantly in women during 3rd trimester. To our knowledge, no previous study has investigated associations between PFAS exposure and concentrations of both SHBG and androgens in pregnant women.

Objective: To investigate associations between maternal PFAS concentrations and levels of SHBG and androgens in pregnancy.

Methods: In Odense Child Cohort (OCC), a single-center study, pregnancy serum concentrations of five PFAS: perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 1,609 eligible women at median gestational week (GW) 12 (25th, 75th percentile: 10, 15). Among these, concentrations of SHBG, calculated Free-T, and TT were assessed in 1,048 pregnant women at median GW 29 (25th, 75th percentile: 28, 30). Multivariate linear regression models were performed to estimate associations between PFAS concentrations and levels of SHBG and androgens.

Results: Included women had a mean age of 30.2 (±4.5 SD) years and median pre-pregnancy BMI of 23.5 (5th, 95th percentiles: 19.2, 32.6) kg/m² and 57.8% were nulliparous. A doubling in PFOS concentration was associated with an increment in SHBG concentration by 2.29% (95% CI: 0.04%, 4.59%) in adjusted analyses. PFOS exposure in the third tertile, as compared to the first tertile, significantly increased SHBG concentrations by 4.60% (95% CI: 0.46%, 8.26%). A significant dose-response relationship was observed across exposure tertiles for PFOS in the association with SHBG. A non-significant inverse association was found between PFAS and Free-T. No significant association was demonstrated between PFAS and TT.

Conclusion and perspectives: Our data suggested that PFOS exposure was associated with higher SHBG concentrations in pregnant women. This increase in SHBG may indirectly be through a PFOS-mediated aromatase induction. Possibly, the increase in SHBG without a compensatory TT increment may result in the non-significant decrease in Free-T. The findings underscore the necessity of the follow-up of children in terms of assessing putative long-term associations with PFAS during childhood.