Sexual dimorphism in cortisol metabolism throughout pubertal development: a longitudinal study

OBJECTIVE: Sex differences in disease susceptibility might be explained by sexual dimorphism in hypothalamic-pituitary-adrenal axis activity, which has been postulated to emerge during puberty. However, studies conducted thus far lacked an assessment of Tanner pubertal stage. This study aimed to assess the contribution of pubertal development to sexual dimorphism in cortisol production and metabolism. METHODS: Participants (n=218), were enrolled from a population-based Netherlands Twin Register. At the ages of 9, 12 and 17 years Tanner pubertal stage was assessed, and early-morning urine samples were collected. Cortisol metabolites were measured with GC-MS/MS, and ratios were calculated, representing cortisol metabolism enzyme activities, such as A-ring reductases, 11β-HSDs and CYP3A4. Cortisol production and metabolism parameters were compared between sexes for pre-pubertal (Tanner stage 1), early-pubertal (Tanner stage 2-3) and late-pubertal (Tanner stage 4-5) stages. RESULTS: Cortisol metabolite excretion rate decreased with pubertal maturation in both sexes, but did not significantly differ between sexes at any pubertal stage, although in girls a considerable decrease was observed between early- and late-pubertal stage (P