Associations of per- and polyfluoroalkyl substances with maternal early second trimester sex-steroid hormones

Diana C Pacyga; George D Papandonatos; Libeth Rosas; Jason Whalen; Sabrina Smith; June-Soo Park; Joseph C Gardiner; Joseph M Braun; Susan L Schantz; Rita S Strakovsky

doi:10.1016/j.ijheh.2024.114380

Associations of per- and polyfluoroalkyl substances with maternal early second trimester sex-steroid hormones

Int J Hyg Environ Health. 2024 Apr 23:259:114380. doi: 10.1016/j.ijheh.2024.114380. Online ahead of print.

Authors

Affiliations

¹ Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA; Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
² Department of Biostatistics, Brown University, Providence, RI 02912, USA.
³ The Beckman Institute, University of Illinois, Urbana-Champaign, IL 61801, USA.
⁴ Michigan Diabetes Research Center Chemistry Laboratory, University of Michigan, Ann Arbor, MI 48109, USA.
⁵ Environmental Chemistry Laboratory, Department of Toxic Substances Control, California Environmental Protection Agency, Berkeley, CA 94710, USA.
⁶ Environmental Chemistry Laboratory, Department of Toxic Substances Control, California Environmental Protection Agency, Berkeley, CA 94710, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94158, USA.
⁷ Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI 48824, USA.
⁸ Department of Epidemiology, Brown University, Providence, RI 02912, USA.
⁹ The Beckman Institute, University of Illinois, Urbana-Champaign, IL 61801, USA; Department of Comparative Biosciences, University of Illinois, Urbana-Champaign, IL 61802, USA.
¹⁰ Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA. Electronic address: strakovs@msu.edu.

PMID: 38657330
DOI: 10.1016/j.ijheh.2024.114380

Abstract

Background/aims: Pregnant women are exposed to persistent environmental contaminants, including per- and polyfluoroalkyl substances (PFAS) that disrupt thyroid function. However, it is unclear if PFAS alter maternal sex-steroid hormone levels, which support pregnancy health and fetal development.

Methods: In Illinois women with relatively high socioeconomic status (n = 460), we quantified perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid, perfluorohexanesulphonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid concentrations in fasting serum samples at median 17 weeks gestation, along with plasma progesterone, testosterone, and estradiol. We evaluated covariate-adjusted associations of ln-transformed hormones with each ln-transformed PFAS individually using linear regression and with the PFAS mixture using quantile-based g-computation (QGComp).

Results: Interquartile range (IQR) increases in PFOS were associated with higher progesterone (%Δ 3.0; 95%CI: -0.6, 6.6) and estradiol (%Δ: 8.1; 95%CI: 2.2, 14.4) levels. Additionally, PFHxS was positively associated with testosterone (%Δ: 10.2; 95%CI: 4.0, 16.7), whereas both PFDeA and PFUdA were inversely associated with testosterone (%Δ: -5.7; 95%CI: -10.3, -0.8, and %Δ: -4.1; 95%CI: -7.6, -0.4, respectively). The IQR-standardized PFAS mixture was not associated with progesterone (%Δ: 1.6; 95%CI: -5.8, 9.2), due equal partial positive (%Δ: 9.2; driven by PFOA) and negative (%Δ: -7.4; driven by PFOS) mixture associations. Similarly, the mixture was not associated with testosterone (%Δ: 5.3; 95%CI: -9.0, 20.1), due to similar partial positive (%Δ: 23.6; driven by PFHxS) and negative (%Δ: -17.4; driven by PFDeA) mixture associations. However, we observed a slightly stronger partial positive (%Δ: 25.6; driven by PFOS and PFUdA) than negative (%Δ: -16.3; driven by PFOA) association resulting in an overall non-significant positive trend between the mixture and estradiol (%Δ: 8.5; 95%CI: -3.7, 20.9).

Conclusion: PFAS mixture modeled using QGComp was not associated with maternal sex-steroid hormones due to potential opposing effects of certain PFAS. Additional prospective studies could corroborate these findings.

Keywords: Estradiol; PFAS; Pregnancy; Progesterone; Quantile-based g-computation; Testosterone.