Bibian van der Voorn

140 CHAPTER 10 ABSTRACT BACKGROUND Gender-specific differences inHPA axis activity have been postulated to emerge during puberty. We conducted a systematic review and meta-analysis to test the hypothesis that gender-specific differences in HPA axis activity are already present in childhood. METHODS From inception to January 2016, PubMed and Embase.com were searched for studies that assessed non-stimulated cortisol in serum or saliva, or cortisol in 24h-urine in healthy males and females aged ≤18yr. Studies were reported conform the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Standardized mean differences (95%CIs) were calculated and analyzed using fixed-effect meta-analysis stratified for age: <8yr (prepubertal) and 8-18yr (peri-/ postpubertal). For comparison,we ran the sameanalysesusing random-effectsmodels. RESULTS Two independent assessors selected 413 out of 6,158 records (7%) for full-text screening, of which 79 articles were included. Of these, 58 (with data on 16,551 subjects) were included in the meta-analysis. Gender differences in cortisol metabolism differed per age group. Boys aged <8yr had 0.18 (0.06 to 0.30) nmol/L higher serum and 0.21 (0.05 to 0.37) nmol/L higher salivary cortisol levels, while between 8-18yr, boys had 0.34 (0.28 to 0.40) nmol/L lower serum and 0.42 (0.38; 0.47) nmol/L lower salivary cortisol levels. In 24h-urine, cortisol was consistently higher in boys, being 0.34 (0.05 to 0.64) and 0.32 (0.17 to 0.47) µg/24h higher in the <8yr and 8-18yr groups, respectively. However, gender-differences in serum cortisol <8 yr and between 8-18 yr were absent when using random-effects models. CONCLUSIONS Gender differences in cortisol metabolism are already present in childhood, with higher salivary cortisol in boys aged <8yr compared to girls. This patternwas reversed after age 8 yr. In contrast, the gender-specific difference in cortisol production as assessed through 24h-urine did not change with age. Although differences were small, and analyses of gender differences in serum cortisol were inconclusive, they might contribute to gender-specific origins of health and disease.