Associations of caffeine and caffeine metabolites with sex hormones among 6-19-year-old children and adolescents.

We aimed to assess the associations between caffeine and its metabolites and sex steroid hormones among children (aged 6-11 years) and adolescents (aged 12-19 years) using data from the U.S. National Health and Nutrition Examination Survey (NHANCES) conducted in 2013-2014. A total of 579 individuals aged 6-19 years with available data on urinary caffeine and its metabolites, as well as serum hormones [total testosterone (TT), estradiol (E), sex hormone-binding globulin (SHBG)], were included. Additionally, the free androgen index (FAI) was calculated as TT/SHBG, and the ratio of TT to E (TT/E) was estimated. Puberty status was defined based on hormone levels (TT ≥ 30 ng/dL in males and E2 ≥ 20 pg/ml in females for high steroid hormone levels; otherwise considered prepuberty). Linear regression, weighted quantile sum (WQS) regression, and Q-gcomp analyses were performed to estimate the associations of individual chemicals or chemical mixtures with sex hormones. Linear regression analyses indicated inverse associations between 12 and 15 caffeine metabolites with SHBG levels in male children and prepubertal boys, respectively. Furthermore, WQS regression demonstrated that caffeine mixtures were inversely associated with E and TT levels in male adolescents and prepubertal boys. Similar results were observed with Q-gcomp analysis. Exposure to caffeine and its metabolites, either individually or as a mixture, was inversely associated with SHBG levels in male children and prepubertal boys. Additionally, caffeine mixtures were associated with decreased levels of E and TT in male adolescents and prepubertal boys.