Reproductive Toxicology · Apr 15, 2026

Associations between pollutants, the regularity of daily sex hormone patterns, and hormone profiles over a complete menstrual cycle

By Winkles JF, Santoro N, El Khoudary SR et al.

This study investigates how elevated pollutant levels in the body are associated with the regularity/complexity of daily urinary sex hormones, identifying relationships and evaluating them in the context of hormonal profile differences. 273 midlife women provided daily measurements of follicle-stimulating hormone (FSH), estrogen conjugates (E1C), pregnanediol glucuronide (PDG), and luteinizing hormone (LH) for a full menstrual cycle. In addition, one-time urine/serum samples were taken testing for per/polyfluoroalkyl substances (PFAS), phthalates, phenols, and metals. Hormone regularity/complexity was measured via distribution and fuzzy entropy (DistEn, FuzzEn) and regressed separately on ordinal pollutant levels. Generally, strong associations exist between elevated pollutant levels and hormonal entropy. The majority trend shows the highest pollutant levels being associated with decreases in hormonal entropy; bisphenol A (phenol) with E1C-DistEn and FSH-FuzzEn, perfluorononanoic acid (PFAS) with FSH-DistEn, perfluorooctanoic acid (PFAS) with LH-FuzzEn, methyl paraben (phenol) with E1C-DistEn, and Thallium (metal) with PDG-DistEn and LH-FuzzEn. Additionally, the highest level of 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid (PFAS) is associated with increased LH-DistEn. These relationships correspond to hormonal profiles indicative of advanced reproductive aging associated with pre/perimenopause, displaying varying degrees of weakened/altered LH peaks, heightened FSH, diminished PDG surges, and late-luteal phase E1C dysfunction. This trend persists after accounting for age and prevalence of anovulatory cycles, indicating that, with the exception of LH-DistEn, lowered entropy may signal instances where elevated pollutant levels in the body relate to early menopause. While LH-DistEn still embodies this pollutant-aging relationship, it may be unique in that elevated DistEn is associated with relatively more hormonal dysregulation.

doi.org/10.1016/j.reprotox.2026.109247 Open access PubMed 41997547 Populations