Association between high DHEAS in 7-year-old girls and metabolic features 4 years after menarche

Premature adrenarche is linked to increased adiposity, enhanced adrenal 11-oxygenated C19 androgen production, and adverse metabolic profiles in childhood. However, it remains unclear whether early elevations in dehydroepiandrosterone sulfate (DHEAS) predict metabolic dysfunction in adolescence or young adulthood.

This longitudinal study included girls from the Growth and Obesity Chilean Cohort Study, all with normal birth weight. DHEAS was measured at ∼7 years (n = 504, 68% follow-up), and participants were reevaluated 4 years after menarche (4YPM, ∼16 years). Girls were classified as having high DHEAS (HD; >75th percentile) or normal DHEAS (ND; ≤75th percentile). Anthropometric, metabolic, and hormonal parameters, including 11-oxygenated C19 steroids, were compared between groups.

At 4YPM, HD girls (n = 96) showed higher body mass index SD score (P < .01), waist-to-height and waist-to-hip ratios (P < .05), and 47% higher mean DHEAS levels (P < .001) than ND girls (n = 249). No differences were observed in glucose, insulin, homeostatic model assessment for insulin resistance, lipid profile, testosterone, SHBG, free androgen index, or 11-oxosteroid concentrations. HD girls exhibited slightly higher mean blood pressure but no increased prevalence of metabolic syndrome in crude or adjusted models (adjusted for birth weight SD score, age at menarche, and body mass index at ∼7 years). Among HD girls, DHEAS at 7 years was not correlated with 11-oxosteroids at 4YPM. Serum 11KA4 was inversely associated with glucose after adjustment (β -.02; 95% CI, -0.04 to -0.006).

Elevated DHEAS at adrenarche persists after puberty without higher bioactive 11-oxosteroids or significant metabolic deterioration, suggesting attenuation of early adverse metabolic features by mid-adolescence.