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Sex specificity in associations between exposure to a mixture of per and poly-fluoroalkyl substances and anxiety among US adults

Journal of Exposure Science & Environmental Epidemiology (2025)Cite this article

Abstract

Background

Exposure to per and poly-fluoroalkyl substances (PFAS) is suggested to interfere with the central nervous system that may affect mental health. Studies on the relationships between exposure to PFAS mixtures and anxiety in humans are rare. This study aimed to evaluate the associations between single and combined exposure to PFAS and anxiety among adults.

Methods

Data were extracted from the National Health and Nutrition Examination Survey (NHANES, 2007–2012). Six serum PFAS concentrations were accessed including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), PFOS (perfluorooctanesulfonic acid), PFHxS (perfluorohexane sulfonate), PFDA (perfluorodecanoic acid), Me-PFOSA-AcOH (2-(N-methylperfluorooctanesulfonamide) acetic acid). The anxiety state was defined through the questionnaire responses of the participants. Weighted logistics regression was used to calculate their odds ratio (OR) and corresponding confidence interval (95% CI) that assessed the relationship between PFAS exposure and anxiety. Moreover, Two different statistical methods including quantile-based g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) were employed to investigate the overall effects of PFAS mixtures on anxiety.

Results

The effects of specific PFAS exposure on anxiety varied by sex. In male participants, one-unit increase in PFDA (OR = 0.62; 95%CI: 0.44, 0.88), PFOA (OR = 0.60; 95%CI: 0.41, 0.87), PFNA (OR = 0.68; 95%CI: 0.46, 0.96) concentrations were inversely linked to anxiety. In female participants, a one-unit increase in PFOA (OR = 1.50; 95%CI: 1.05, 2.14) concentration was associated with anxiety. Analysis of Qgcomp demonstrated that PFAS mixtures were negatively associated with anxiety in males (OR = 0.85; 95%CI: 0.74, 0.99), and were positively associated with anxiety in females(OR = 1.16; 95%CI: 1.01, 1.33). Analysis of BKMR suggested that PFAS mixtures were negatively associated with anxiety in the males, while its associations with anxiety were positive in the females.

Impact

  • Although a growing number of studies have focused on the relationship between PFAS and anxiety, most have been performed based on animal observations rather than human populations, and the combined effects of PFAS mixtures on anxiety have not been evaluated. To address these gaps, this study first explored the associations between individual PFAS and PFAS mixture exposures and anxiety among US adults. Using data from the National Health and Nutrition Examination Survey, we demonstrated that co-exposure to a mixture of PFAS was negatively associated with anxiety in males, and its association was contrary in females.

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Fig. 1
Fig. 2: Qgcomp model regression joint effect (95% CI) for each PFAS with anxiety.
Fig. 3: Combined effects of the PFAS as a mixture on anxiety.

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Data availability

The datasets used for these analyses are publicly available (https://wwwn.cdc.gov/nchs/nhanes/Default.aspx).

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Acknowledgements

The authors thank the National Health and Nutrition Examination Survey for publicly available data.

Funding

This manuscript was supported by the Scientific Research Promotion Plan of Anhui Medical University (2021xkjT013), Project of Anhui Provincial Academic and Technical Leaders for Scientific Research Activities (2022D321), Projects of Anhui Provincial Key Laboratory of Population Health and Aristogenics (JKYS20225), and National Natural Science Foundation of China (No.72374005).

Author information

Author notes

  1. These authors contributed equally: Xiaoguo Hua, Rui Hu, Cai Chen.

Authors and Affiliations

  1. Office of Medical Insurance Management, The Second Affiliated Hospital, Anhui Medical University, Hefei, China

    Xiaoguo Hua & Xiqiu Feng

  2. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China

    Xiaoguo Hua & Xiujun Zhang

  3. Department of Clinical Teaching Management, The First Affiliated Hospital, Anhui University of Traditional Chinese Medicine, Hefei, China

    Rui Hu

  4. Department of Emergency, The Second Affiliated Hospital of Anhui Medical University, Hefei, China

    Cai Chen

  5. Department of Health Data Science, School of Health Care Management, Anhui Medical University, Hefei, China

    Jiangjie Sun

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Contributions

Xiaoguo Hua performed the data analyses and wrote the manuscript. Rui Hu revised the final typescript. Cai Chen searched and evaluated the retrieved articles. Xiqiu Feng and Jiangjie Sun contributed to the conception of the study. Xiujun Zhang was responsible for the communication of the paper.

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Correspondence to Xiujun Zhang.

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The application of every technique followed all applicable rules and regulations. The US National Center for Healthcare Statistics (NCHS) granted permission for the 2007–2012 NHANES to be conducted.

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Hua, X., Hu, R., Chen, C. et al. Sex specificity in associations between exposure to a mixture of per and poly-fluoroalkyl substances and anxiety among US adults. J Expo Sci Environ Epidemiol (2025). https://doi.org/10.1038/s41370-024-00741-3

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