Female-specific associations of serum perfluoroalkyl and polyfluoroalkyl substances with sex hormonal/insulin dysregulation: An integrated population-based study
Background: Ubiquitous perfluoroalkyl/polyfluoroalkyl substances (PFASs) exhibit sex-differential blood accumulation. However, sex- and age-specific links between PFASs and insulin-hormone dysregulation remain unknown. Methods: This population-based study utilized survey-weighted data from the Natio...
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Elsevier
2025-06-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325006098 |
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| author | Le-Xin Yang Junyu Zhai Zi-Jiang Chen Yanzhi Du |
| author_facet | Le-Xin Yang Junyu Zhai Zi-Jiang Chen Yanzhi Du |
| author_sort | Le-Xin Yang |
| collection | DOAJ |
| description | Background: Ubiquitous perfluoroalkyl/polyfluoroalkyl substances (PFASs) exhibit sex-differential blood accumulation. However, sex- and age-specific links between PFASs and insulin-hormone dysregulation remain unknown. Methods: This population-based study utilized survey-weighted data from the National Health and Nutrition Examination Survey 2013–2016. Correlations between PFASs and sex hormone- or insulin-related indicators were assessed using a survey-weighted generalized linear model (SWGLM) for individual analyses and weighted quantile sum (WQS) regression for mixture analyses, stratified by sex and age. The mixture-related findings were validated with Bayesian kernel machine regression (BKMR) and further examined through stratification by menopausal status. Moreover, we investigated whether homeostatic model assessment of insulin resistance (HOMA-IR) mediated the relationships between sex hormones and monomethyl branched isomers of perfluorooctane sulfonate (Sm-PFOS) sex-specifically. Results: The following results persisted only in females. In SWGLM, linear perfluorooctanoate (n-PFOA) and homeostatic model assessment of β cell function (HOMA-β) were positively correlated in females, with this correlation strengthening in those aged ≥ 60. In WQS, PFAS mixture was positively associated with total testosterone/estradiol (TT/E2) and negatively associated with estradiol (E2) in females, but not in postmenopausal participants; the BKMR demonstrated trends consistent with prior findings. These associations intensified in females aged 20–59, with n-PFOA and perfluorohexane sulfonic acid (PFHxS) being main pollutants in the 20–39 and 40–59 age groups, respectively in WQS. The relationships between Sm-PFOS and both free androgen index and sex hormone-binding globulin (SHBG) were mediated by HOMA-IR. Conclusions: This cross-sectional study reveals female-specific associations between PFASs and insulin-hormone imbalance, suggesting multifaceted influences of PFASs on female endocrinology. |
| format | Article |
| id | doaj-art-77a5e7efd5dd406ab334531cee5140bf |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-77a5e7efd5dd406ab334531cee5140bf2025-08-20T03:54:07ZengElsevierEcotoxicology and Environmental Safety0147-65132025-06-0129811827310.1016/j.ecoenv.2025.118273Female-specific associations of serum perfluoroalkyl and polyfluoroalkyl substances with sex hormonal/insulin dysregulation: An integrated population-based studyLe-Xin Yang0Junyu Zhai1Zi-Jiang Chen2Yanzhi Du3Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics; Shanghai 200135, ChinaCenter for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics; Shanghai 200135, ChinaCenter for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics; Shanghai 200135, China; Center for Reproductive Medicine, Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong Provincial Key Laboratory of Reproductive Medicine, Shandong 250012, China; NMU-SD Suzhou Collaborative Innovation Center for Reproductive Medicine, China; Corresponding author at: Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai 200135, China.Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics; Shanghai 200135, China; Correspondence to: 845 Lingshan Road, Shanghai 200135, China.Background: Ubiquitous perfluoroalkyl/polyfluoroalkyl substances (PFASs) exhibit sex-differential blood accumulation. However, sex- and age-specific links between PFASs and insulin-hormone dysregulation remain unknown. Methods: This population-based study utilized survey-weighted data from the National Health and Nutrition Examination Survey 2013–2016. Correlations between PFASs and sex hormone- or insulin-related indicators were assessed using a survey-weighted generalized linear model (SWGLM) for individual analyses and weighted quantile sum (WQS) regression for mixture analyses, stratified by sex and age. The mixture-related findings were validated with Bayesian kernel machine regression (BKMR) and further examined through stratification by menopausal status. Moreover, we investigated whether homeostatic model assessment of insulin resistance (HOMA-IR) mediated the relationships between sex hormones and monomethyl branched isomers of perfluorooctane sulfonate (Sm-PFOS) sex-specifically. Results: The following results persisted only in females. In SWGLM, linear perfluorooctanoate (n-PFOA) and homeostatic model assessment of β cell function (HOMA-β) were positively correlated in females, with this correlation strengthening in those aged ≥ 60. In WQS, PFAS mixture was positively associated with total testosterone/estradiol (TT/E2) and negatively associated with estradiol (E2) in females, but not in postmenopausal participants; the BKMR demonstrated trends consistent with prior findings. These associations intensified in females aged 20–59, with n-PFOA and perfluorohexane sulfonic acid (PFHxS) being main pollutants in the 20–39 and 40–59 age groups, respectively in WQS. The relationships between Sm-PFOS and both free androgen index and sex hormone-binding globulin (SHBG) were mediated by HOMA-IR. Conclusions: This cross-sectional study reveals female-specific associations between PFASs and insulin-hormone imbalance, suggesting multifaceted influences of PFASs on female endocrinology.http://www.sciencedirect.com/science/article/pii/S0147651325006098PFASSex hormonesInsulin resistanceSex differencesAge groups |
| spellingShingle | Le-Xin Yang Junyu Zhai Zi-Jiang Chen Yanzhi Du Female-specific associations of serum perfluoroalkyl and polyfluoroalkyl substances with sex hormonal/insulin dysregulation: An integrated population-based study Ecotoxicology and Environmental Safety PFAS Sex hormones Insulin resistance Sex differences Age groups |
| title | Female-specific associations of serum perfluoroalkyl and polyfluoroalkyl substances with sex hormonal/insulin dysregulation: An integrated population-based study |
| title_full | Female-specific associations of serum perfluoroalkyl and polyfluoroalkyl substances with sex hormonal/insulin dysregulation: An integrated population-based study |
| title_fullStr | Female-specific associations of serum perfluoroalkyl and polyfluoroalkyl substances with sex hormonal/insulin dysregulation: An integrated population-based study |
| title_full_unstemmed | Female-specific associations of serum perfluoroalkyl and polyfluoroalkyl substances with sex hormonal/insulin dysregulation: An integrated population-based study |
| title_short | Female-specific associations of serum perfluoroalkyl and polyfluoroalkyl substances with sex hormonal/insulin dysregulation: An integrated population-based study |
| title_sort | female specific associations of serum perfluoroalkyl and polyfluoroalkyl substances with sex hormonal insulin dysregulation an integrated population based study |
| topic | PFAS Sex hormones Insulin resistance Sex differences Age groups |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325006098 |
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