Association of Personal Care and Consumer Product Chemicals with Long-Term Amenorrhea: Insights into Serum Globulin and STAT3

Abstract

Chemicals in personal care and consumer products are suspected to disrupt endocrine function and affect reproductive health. However, the link between mixed exposure and long-term amenorrhea is not well understood. This study analyzed data from 684 women (2013-2018 National Health and Nutrition Examination Survey) to assess exposure to eight polyfluorinated alkyl substances (PFASs), 15 phthalates (PAEs), six phenols, and four parabens. Various statistical models for robustness tests and mediation analysis were used to explore associations with long-term amenorrhea and the role of serum globulin. Biological mechanisms were identified through an integrated strategy involving target analysis of key chemicals and long-term amenorrhea intersections, pathway analysis, and target validation. Results showed that women with long-term amenorrhea had higher exposure levels of Perfluorodecanoic acid, Perfluorohexane sulfonic acid (PFHxS), Perfluorononanoic acid, n-perfluorooctanoic acid (n_PFOA), n-perfluorooctane sulfonic acid, and Perfluoromethylheptane sulfonic acid isomers. Logistic regression with different adjustments consistently found significant associations between elevated PFAS concentrations and increased long-term amenorrhea risk, confirmed by Partial Least Squares Discriminant Analysis. Mediation analysis revealed that serum globulin partially mediated the relationship between PFAS exposure and long-term amenorrhea. Network and target analysis suggested that PFHxS and n_PFOA may interact with Signal Transducer and Activator of Transcription 3 (STAT3). This study highlights significant associations between PFAS exposure, particularly PFHxS and n_PFOA, and long-term amenorrhea, with serum globulin and STAT3 serving as mediators in the underlying mechanisms.

Keywords: long-term amenorrhea; mediation analysis; mixed exposure; molecular docking; personal care products; polyfluorinated alkyl substances.

Figure 1

Flow chart of the screening process from NHANES (2013–2018).

Figure 2

Identification of common targets, interaction networks, and target validation between PFHxS, n_PFOA, and long-term amenorrhea. (A) Venn diagram of common targets between PFHxS, n_PFOA, and long-term amenorrhea. (B,C) PPI network for PFHxS, n_PFOA, and long-term amenorrhea targets. (D,E) KEGG and GO pathway analyses of PFHxS and n_PFOA targets in long-term amenorrhea. (F,G) Molecular docking analysis of PFHxS and n_PFOA binding to STAT3 protein.