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. 2025 Jun 16;28(7):112876.
doi: 10.1016/j.isci.2025.112876. eCollection 2025 Jul 18.

Associations of internal persistent organic pollutant levels with sex hormones: An analysis by sex and menopausal status in a Spanish cohort

Celia Pérez-Díaz  1   2 , Ruth Echeverría  1   3 , Francisco M Pérez-Carrascosa  1   2 , Inmaculada Salcedo-Bellido  1   2   4 , Pilar Requena  1   2   4 , Rocío Barrios-Rodríguez  1   2   4 , Juan José Ramos  5 , Nicolás Olea  2   4   6 , Mariana F Fernández  2   4   6 , Piedad Martín-Olmedo  2   7 , Juan Pedro Arrebola  1   2   4
Affiliations

Associations of internal persistent organic pollutant levels with sex hormones: An analysis by sex and menopausal status in a Spanish cohort

Celia Pérez-Díaz et al. iScience. .

Abstract

The aim of this study was to investigate associations between human exposure to persistent organic pollutants and sex hormone levels. The study population (n = 253) was a subsample of GraMo adult cohort, recruited in 2003-2004 in two hospitals from Granada, Spain. Exposure was estimated by analyzing samples of adipose tissue (3 organochlorine pesticides and 3 polychlorinated biphenyls) and serum (4 per- and polyfluoroalkyl substances). Data analyses included robust linear regression and weighted quantile sum regression. In men, PFNA (positively) and PCB-138 (negatively) were associated with testosterone. In premenopausal women, OCPs and PCBs were negatively associated with estradiol and SHBG. PFHxS was inversely related to luteinizing hormone. Additionally, PCB-153 and -180 was positively associated with testosterone. The mixture of PCBs/OCPs was positively associated with testosterone in women and with FSH in men. Our results highlight the potential of chemical mixture exposure to alter sex hormone homeostasis, depending on sex and menopausal status.

Keywords: Environmental health; Environmental science.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Diagram of the sample selection process and subgroups for individual pollutant and multipollutant analyses POPs: persistent organic pollutants; PCBs: polychlorinated biphenyls; OCPs: organochlorine pesticides; PFAS: per- and polyfluoroalkyl substances.
Figure 2
Figure 2
Relationship between serum per- and polyfluoroalkyl substances (PFAS) concentrations (μg/L) and age Scatterplots represent unadjusted linear regression models non-adjusted for confounders variables. PFOA: perfluorooctanoic acid; PFNA: perfluorononanoic acid; PFHxS: perfluorohexane sulfonic acid; PFOS: perfluorooctane sulfonic acid.
Figure 3
Figure 3
Correlation matrix between POPs in the study population Cells display the Spearman’s correlation test rho value, whose value ranges between 1 (blue) and - 1 (red). PCB: polychlorinated biphenyl; HCB: hexachlorobenzene; β-HCH: beta-hexachlorocyclohexane; p,p’-DDE: p,p’-dichlorodiphenyldichloroethylene; PFOA: perfluorooctanoic acid; PFNA: perfluorononanoic acid; PFHxS: perfluorohexane sulfonic acid; PFOS: perfluorooctane sulfonic acid.
Figure 4
Figure 4
Percentage contribution of the mixture of PCBs and OCPs in the WQS significant models Models for men were adjusted for age, BMI, smoking habit, alcohol consumption and education level. For women they were also adjusted for number of children, breastfeeding and use of contraceptives. The concentrations of PCBs/OCPs were logarithmically transformed. The covariates were not transformed. The bar length represents the weight of each contaminant in percentage. SE: standard error; WQS: weighted quantile sum; PCBs: polychlorinated biphenyls; OCPs: organochlorine pesticides; FSH: follicle-stimulating hormone; SHBG: sex hormone binding globulin; TT: total testosterone; HCB: hexachlorobenzene; β-HCH: beta-hexachlorocyclohexane; p,p’-DDE: p,p’-dichlorodiphenyldichloroethylene.
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