Associations of urinary non-persistent endocrine disrupting chemical biomarkers with early-to-mid pregnancy plasma sex-steroid and thyroid hormones

Brad A. Ryva, Diana C. Pacyga, Kaitlyn Y. Anderson, Antonia M. Calafat, Jason Whalen, Max T. Aung, Joseph C. Gardiner, Joseph M. Braun, Susan L. Schantz, Rita S. Strakovsky

Research output: Contribution to journalArticlepeer-review


Background/Objectives: Pregnant women are exposed to numerous endocrine disrupting chemicals (EDCs) that can affect hormonal pathways regulating pregnancy outcomes and fetal development. Thus, we evaluated overall and fetal sex-specific associations of phthalate/replacement, paraben, and phenol biomarkers with sex-steroid and thyroid hormones. Methods: Illinois women (n = 302) provided plasma for progesterone, estradiol, testosterone, free T4 (FT4), total T4 (TT4), and thyroid stimulating hormone (TSH) at median 17 weeks gestation. Women also provided up-to-five first-morning urine samples monthly across pregnancy (8–40 weeks), which we pooled to measure 19 phthalate/replacement metabolites (reflecting ten parent compounds), three parabens, and six phenols. We used linear regression to evaluate overall and fetal sex-specific associations of biomarkers with hormones, as well as weighted quantile sum and Bayesian kernel machine regression (BKMR) to assess cumulative associations, non-linearities, and chemical interactions. Results: In women of relatively high socioeconomic status, several EDC biomarkers were associated with select hormones, without cumulative or non-linear associations with progesterone, FT4, or TT4. The biomarker mixture was negatively associated with estradiol (only at higher biomarker concentrations using BKMR), testosterone, and TSH, where each 10% mixture increase was associated with −5.65% (95% CI: −9.79, −1.28) lower testosterone and −0.09 μIU/mL (95% CI: −0.20, 0.00) lower TSH. Associations with progesterone, testosterone, and FT4 did not differ by fetal sex. However, in women carrying females, we identified an inverted u-shaped relationship of the mixture with estradiol. Additionally, in women carrying females, each 10% increase in the mixture was associated with 1.50% (95% CI: −0.15, 3.18) higher TT4, whereas in women carrying males, the mixture was associated with −1.77% (95% CI: −4.08, 0.58) lower TT4 and −0.18 μIU/mL (95% CI: −0.33, −0.03) lower TSH. We also identified select chemical interactions. Conclusion: Some biomarkers were associated with early-to-mid pregnancy hormones. There were some sex-specific and non-linear associations. Future studies could consider how these findings relate to pregnancy/birth outcomes.

Original languageEnglish (US)
Article number108433
JournalEnvironment international
StatePublished - Jan 2024


  • Endocrine disrupting chemical
  • Fetal sex
  • Hormone
  • Paraben
  • Phenol
  • Phthalate
  • Pregnancy

ASJC Scopus subject areas

  • General Environmental Science


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