Jul 2026· International Journal of Environmental Health Research· pp.
1-11
· 0 citations· 26 references
Medicine
TL;DR
It is suggested that formaldehyde exposure may be associated with altered sex steroid hormone profiles in female adolescents because of inverse associations between formaldehyde and several sex steroid hormones observed across age-sex groups.
Abstract
Experimental studies suggest that formaldehyde may disrupt reproductive and endocrine function, but human evidence remains limited. We examined the association between formaldehyde exposure, measured as hemoglobin adducts, and serum sex steroid hormones among children (6-11 years) and adolescents (12-19 years) participating in NHANES 2013-2016. Multivariable regression models were used to evaluate associations between formaldehyde and total testosterone (TT), estradiol (E2), sex hormone-binding globulin (SHBG), free testosterone, free estradiol (FE2), and the TT/E2 ratio. False discovery rate (FDR) correction was applied to account for multiple comparisons, and restricted cubic spline models were used to assess potential non-linear dose - response relationships. After FDR correction, significant associations were observed only among female adolescents. Each doubling of formaldehyde concentration was associated with lower E2 (-55.74%; 95% CI: -73.43, -26.24%) and a higher TT/E2 ratio (96.84%; 95% CI: 18.26, 227.61). Restricted cubic spline analyses supported non-linear dose - response relationships. Although inverse associations between formaldehyde and several sex steroid hormones were observed across age-sex groups, most did not remain significant after FDR correction. These findings suggest that formaldehyde exposure may be associated with altered sex steroid hormone profiles in female adolescents.
Phthalates (PAEs) and benzophenones (BPs) are ubiquitous endocrine-disrupting chemicals, and exposure to them is thought to disrupt pubertal development. However, epidemiological evidence regarding their real-world, combined associations with early puberty timing (EPT) in girls remains limited and inconsistent. This case-control study enrolled a total of 147 girls, comprising 63 EPT cases and 84 healthy controls. Urinary concentrations of seven PAE and two BP metabolites were quantified. Single-pollutant associations and exposure-response relationships were evaluated using multivariable logistic regression and restricted cubic splines (RCS). To investigate potential modification of these associations by weight status, we conducted subgroup analyses. Furthermore, the overall joint association of the chemical mixture was quantified applying Bayesian kernel machine regression (BKMR) and quantile g-computation (Qgcomp). In single-pollutant models, MnBP, BP-8, MODP, and MMP were positively associated with the risk of EPT. Stratified analyses indicated that these associations remained consistent across different weight strata, with no significant interaction by weight status. In multi-pollutant analyses, Qgcomp revealed a significant positive joint association of the chemical mixture with EPT (OR=1.36; 95% CI: 1.12, 1.65), which was consistently supported by the BKMR models. Notably, MnBP and BP-8 emerged as the primary contributors of this combined association. Our findings highlight that co-exposure to specific PAE and BP metabolites, particularly MnBP and BP-8, is positively associated with EPT in girls. Future prospective cohorts are necessary to validate these results and uncover the biological pathways.
Zhi Li, Jing-Yi Tang, Yang Chen et al.· Ecotoxicology and Environmen...· 0 citations
Organophosphate esters (OPEs) may disrupt hormonal balance, but their specific effects in pre- and post-menopausal women have been underexplored. This investigation delves into the menopause-specific associations of OPEs with sex hormones in the National Health and Nutrition Examination Survey, 2013-2016. We included 817 premenopausal and 657 postmenopausal women. Survey-weighted multivariable linear regression, restricted cubic splines (RCS), principal component analysis (PCA), and quantile-based g computation (qgcomp) models were conducted to investigate the associations of OPE metabolites and OPEs mixture with sex hormones in pre- and postmenopausal women. In postmenopausal women, bis(2-chloroethyl) phosphate (BCEP) and Bis(1,3-dichloro-2-propyl) phosphate (BDCPP) were negatively associated with testosterone (T) (BCEP: β = -0.06 [-0.10, -0.01]; BDCPP: β = -0.07 [-0.13, -0.01]) and free androgen index (FAI) (BCEP: β = -0.08 [-0.13, -0.02]; BDCPP: β = -0.06 [-0.12, -0.01]). Diphenyl phosphate (DPHP) was also negatively associated with FAI (β = -0.08 [-0.14, -0.02]). RCS analyses revealed non-linear exposure-response relationships between DPHP and T, between BDCPP and estrogen (E2), and between BDCPP and DPHP and the T/E2 ratio. PCA and qgcomp analyses consistently found negative associations between the OPEs mixture and T and FAI. Conversely, in premenopausal women, BCEP was linearly and positively associated with sex hormone-binding globulin (SHBG) (β = 0.05 [0.01,0.09]), whereas DPHP showed a nonlinear relationship with SHBG, with a curve rising then plateauing. Overall, OPEs, alone or as mixtures, might lower T and FAI levels in postmenopausal women. In contrast, BCEP and DPHP might increase SHBG levels in premenopausal women.
BACKGROUND
Aromatic amines (AAs) have rarely been studied in the context of pregnancy despite their ubiquity and known toxicity. To our knowledge, no study has investigated the relationship between AAs and F2-isoprostanes, which are linked to adverse maternal and child health outcomes.
METHODS
Our analytic sample included 176 participants from the Chemicals in Our Bodies prospective birth cohort. Thirty-six AAs and four F2-isoprostanes (biomarkers of oxidative stress) were measured in mid-pregnancy urine. We focused on six AAs that were detected in at least 50% of participants and calculated their molar sum (ΣAA). An additional six AAs that were detected in 20-49% of participants were analyzed as binary variables. Generalized additive mixed models were used to assess non-linearity, and linear regression models were used to examine associations between individual AAs and individual oxidative stress biomarkers, adjusting for confounders.
RESULTS
Most AAs were associated with significant increases in oxidative stress biomarkers. Increasing concentrations of ΣAA were significantly associated with 8-iso-PGF2α (β=0.25, 95% confidence interval [CI]=0.1, 0.41) and PGF2α (β=0.21, CI=0.04, 0.39). Additionally, the individual AAs o/m-toluidine and 4-chloroaniline were associated with significant increases in 8-iso-PGF2α and PGF2α.
CONCLUSIONS
Our study is the first to investigate the relationship between AAs and F2-isoprostanes during pregnancy. This study found that several AAs are associated with higher levels of oxidative stress, highlighting one potential mechanism linking AAs to adverse maternal-child health outcomes.
Madeline Chandler, T. Woodruff, R. Morello-Frosch et al.· Environmental Research· 0 citations
Phthalates are widespread endocrine-disrupting chemicals that may subtly alter thyroid homeostasis, although the influence of sex and adiposity on these associations remains unclear. This cross-sectional study investigated the associations of urinary monoethyl phthalate (MEP) and mono(2-ethylhexyl) phthalate (MEHP) with thyroid function according to sex and body mass index (BMI). The study included 201 metabolically healthy adults aged 18-57 years from Serbia. First-morning urine samples were analyzed for phthalate metabolites by gas chromatography-mass spectrometry, while serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured using a chemiluminescent immunoassay. Participants were classified as lean or overweight and obese, and associations were evaluated using group comparisons and hierarchical multiple linear regression. MEP and MEHP concentrations were above the limit of quantification (LOQ) in 31.84% and 21.89% of samples, respectively. Overweight and obese participants with MEP concentrations above the LOQ had higher FT4 levels than those with concentrations below the LOQ, whereas lean participants with MEHP above the LOQ had lower FT4 levels. Regression analyses identified a significant interaction among MEP, BMI, and sex for TSH, with higher MEP associated with higher TSH primarily in overweight and obese women. A significant interaction among MEHP, BMI, and sex was also observed for FT3, although the inverse association in lean men was only marginally significant. Urinary MEP and MEHP were associated with subtle, sex- and adiposity-dependent variations in thyroid hormone levels within physiological ranges. These exploratory findings require confirmation in larger longitudinal studies using repeated exposure measurements.
I. Bajkin, N. Milić, N. Milošević et al.· Biomolecules & biomedicine· 0 citations
BACKGROUND
Perfluoroalkyl substances (PFAS) are persistent environmental chemicals that may affect vitamin D levels. Epidemiologic findings remain inconsistent, and have not explored associations in Hispanic populations, who experience disproportionate PFAS exposure and vitamin D insufficiency.
OBJECTIVES
To quantify associations between plasma PFAS concentrations and serum 25-hydroxyvitamin D (25(OH)D) levels in Hispanic children.
METHODS
Participants (n=106) were enrolled in the Vidas Activas Familias Saludables (VALE) study, a culturally tailored 10-week lifestyle intervention for Hispanic children aged 4-11 years. Plasma PFAS were measured at pre-intervention using liquid chromatography-tandem mass spectrometry, and serum 25(OH)D was assessed pre- and post-intervention using ELISA kits. Linear mixed regression models estimated associations between individual PFAS and 25(OH)D, adjusting for confounders. Principal component analysis (PCA) was used to identify co-exposure to PFAS mixtures.
RESULTS
Higher plasma PFHxS concentrations were associated with higher serum 25(OH)D levels at pre- and post-intervention (mean difference (MD): 5.63 ng/mL per log increase, 95% CI: 1.81, 9.37). Four components were retained from the PCA. Greater co-exposure to PFOA, PFNA, and PFHpA (MD: 1.94 ng/mL, 95% CI: 0.37, 3.81), and co-exposure to PFOS and PFHxS (MD: 4.60 ng/mL, 95% CI: 2.75, 7.35), were associated with higher serum 25(OH)D. Associations were strongest among children <8 years old and males.
CONCLUSIONS
PFAS exposure, individually and as mixtures, was associated with higher 25(OH)D in Hispanic children, particularly among younger children and males. Larger longitudinal studies of children with diverse racial and ethnic identities are needed to confirm age- and sex-specific PFAS-vitamin D associations.
Rooshna Mohsin, R. Gerona, Sina Gallo et al.· Environmental Research· 0 citations
Sex steroid hormones, including estradiol (E2), estrone (E1), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), have been implicated in the development of female malignancies (FMs), yet their independent and combined effects remain unclear. We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES). Weighted logistic regression, restricted cubic spline modeling, and chi-square trend tests were applied to evaluate dose-response associations. Machine learning algorithms, including Bayesian Kernel Machine Regression, Extreme Gradient Boosting, Shapley Additive Explanations, Least Absolute Shrinkage and Selection Operator regression, and Random Forest, were used to explore nonlinear relationships and assess variable importance in an exploratory manner. Sensitivity analyses confirmed the robustness of the findings. A total of 2108 participants were included. Higher FSH and LH levels were associated with increased odds of FMs, whereas higher E2 levels were associated with lower odds. In exploratory machine learning analyses, FSH and E1 were consistently ranked as important predictors of FMs. In this cross-sectional analysis, LH and FSH were associated with increased odds of FM, while higher E2 levels were inversely associated with malignancy risk. Exploratory machine learning analyses highlighted additional nonlinear patterns involving E2 and E1.
