Adrenal androgen mediates the association between obesity and accelerated skeletal maturation in children and adolescents.

BACKGROUND: Childhood obesity is associated with advanced bone age (BA), but the underlying endocrine mechanisms remain unclear. We investigated the mediating role of dehydroepiandrosterone sulfate (DHEA-S) in the relationship between adiposity and skeletal maturation. METHODS: This retrospective study included 1,252 children aged 4-12 years from a single center. Skeletal maturation was assessed using the BA-to-chronological age (CA) ratio. Advanced maturation was defined as BA/CA > 1.1. Mediation analysis was performed to evaluate whether DHEA-S explains the association between BMI SDS and skeletal maturation. RESULTS: Body mass index standard deviation score (BMI SDS) and DHEA-S were independently associated with the BA/CA ratio (p < 0.05). In boys younger than 9 years, DHEA-S demonstrated good discriminative performance for advanced maturation (Area under the curve = 0.817). Mediation analysis showed that DHEA-S significantly mediated the association between BMI and BA/CA in boys < 9 years (β = 0.512, p = 0.024) and in girls ≥ 8 years (β = 0.377, p = 0.003). In young boys, the direct effect of BMI became non-significant after inclusion of DHEA-S, consistent with substantial mediation by adrenal androgens. CONCLUSIONS: Adrenal androgen activity, reflected by DHEA-S, represents a significant endocrine pathway linking obesity to accelerated skeletal maturation. The magnitude of this mediation varies by age and sex, highlighting developmentally specific windows of endocrine-metabolic interaction in growing children.