Association of formaldehyde with sex steroid hormones in US children and adolescents (NHANES 2013-2016).

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.