Perfluoroalkyl Substance Exposure Was Negatively Associated With Cortisone Levels in Pregnancy

By Anja Fenger Dreyer, Richard Christian Jensen, Dorte Glintborg, Anne Vibeke Schmedes, Ivan Brandslund, Flemming Nielsen, Henriette Boye Kyhl, Tina Kold Jensen, and Marianne Andersen
J Endocr Soc
May 19, 2020
DOI: 10.1210/jendso/bvaa046.2015

Introduction: During pregnancy, maternal cortisol levels are increased threefold by third trimester. The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD, isoforms 1 and 2) regulates cortisol levels by the conversion between cortisol and cortisone. Perfluoroalkyl substances (PFAS) are persistent chemicals with suspected endocrine disrupting abilities applied in consumer products. PFAS have been reported to inhibit 11β-HSD1 and 11β-HSD2, which could lead to reduced levels of cortisol and cortisone.

Aim: To investigate a possible effect of early pregnancy PFAS exposure on late pregnancy activity of 11β-HSD1 and 11β-HSD2 assessed by cortisol and cortisone levels in urine and blood samples.

Methods: The study is part of the prospective cohort study, Odense Child Cohort (OCC). A total of 1,826 pregnant women had serum (S) concentrations of five PFAS (Perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA)) measured in first trimester (median gestational week (GW) 11). Diurnal urinary (dU) cortisol and cortisone (n=344), and S-cortisol (n=1,048) were measured in third trimester (median GW 27).

Results: In multiple regression analyses, a two-fold increase in S-PFOS was significantly associated with lower dU-cortisone (β=-9.1%, p<0.05) and higher dU-cortisol/dU-cortisone (dU-C/C) (β=9.3%, p<0.05). The same trend was demonstrated for PFOA, PFHxS, PFNA, and PFDA. In crude models, a doubling in PFOS, PFOA, PFHxS, and PFNA concentrations were associated with a significant increase in S-cortisol, however, these associations became insignificant after adjustment.

Conclusion: Early pregnancy concentrations of maternal S-PFAS were inversely associated with late pregnancy dU-cortisone, indicating reduced activity of 11β-HSD2.

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