Exposure to metals and the disruption of sex hormones in 6–19 years old children: An exploration of mixture effects

Background: Individual metals have been linked to sex hormones disruption, but the associations of metals mixture are rarely examined among children. Methods: A total of 1060 participants of 6–19-year-old who participated in the National Health and Nutrition Examination Survey (2013–2016) were included. Eighteen metals were quantified in the whole blood and urine. Sex hormones were measured in serum, including total testosterone (TT), estradiol (E2), and sex hormone binding globulin (SHBG). In addition, free androgen index (FAI) and the ratio of TT to E2 were calculated. Bayesian kernel machine regression and latent class analysis were performed to assess the associations of metals mixture and exposure patterns of metals at varied levels with sex hormones while adjusting for selected covariates. All analyses were conducted by sex-age and sex-puberty groups to explore the potential sex-dimorphic effects. Results: Exposure to metals mixture was associated with elevated levels of FAI and E2 among 12–19 years old girls. Moreover, the exposure pattern of metals that was characterized by high levels of blood and urinary cadmium, blood manganese, and urinary cobalt was associated with elevated E2 and reduced TT/E2 levels among girls of 12–19 years old. However, the associations of metals mixture with sex hormones were overall nonsignificant among boys. Nevertheless, metals exposure pattern that was characterized by high levels of blood lead, urinary barium, strontium, and lead but comparatively low levels of the other metals was consistently associated with reduced levels of FAI and E2 but elevated levels of TT/E2 and SHBG among boys of 12–19 years old. Conclusion: Metals mixture and exposure patterns that were dominated by high levels of certain metals were associated with sex hormones imbalance among 12–19 years old children in a sex-dimorphic pattern, with the identified individual metals that drove the associations of metals mixture varied by sex.