TY - JOUR
T1 - Gender-specific differences in hypothalamus-pituitary-adrenal axis activity during childhood
T2 - a systematic review and meta-analysis
AU - van der Voorn, Bibian
AU - Hollanders, Jonneke J.
AU - Ket, Johannes C. F.
AU - Rotteveel, Joost
AU - Finken, Martijn J. J.
N1 - Publisher Copyright: © 2017 The Author(s). Copyright: Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/1/19
Y1 - 2017/1/19
N2 - Background: Gender-specific differences in hypothalamus-pituitary-adrenal (HPA) 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 24-h urine in healthy males and females aged ≤18 years. Studies that conform with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement were reported. Standardized mean differences (95% CIs) were calculated and analyzed using fixed-effect meta-analysis stratified for age: <8 years (prepubertal) and 8-18 years (peri-/postpubertal). For comparison, we ran the same analyses using random-effects models. Results: Two independent assessors selected 413 out of 6158 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 <8 years had 0.18 (0.06; 0.30) nmol/L higher serum and 0.21 (0.05; 0.37) nmol/L higher salivary cortisol levels, while between 8 and 18 years, boys had 0.34 (0.28; 0.40) nmol/L lower serum and 0.42 (0.38; 0.47) nmol/L lower salivary cortisol levels. In 24-h urine, cortisol was consistently higher in boys, being 0.34 (0.05; 0.64) and 0.32 (0.17; 0.47) μg/24 h higher in the <8- and 8-18-year groups, respectively. However, gender-differences in serum cortisol <8 years and between 8 and 18 years 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 <8 years compared to girls. This pattern was reversed after the age of 8 years. In contrast, the gender-specific difference in cortisol production as assessed through 24-h 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.
AB - Background: Gender-specific differences in hypothalamus-pituitary-adrenal (HPA) 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 24-h urine in healthy males and females aged ≤18 years. Studies that conform with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement were reported. Standardized mean differences (95% CIs) were calculated and analyzed using fixed-effect meta-analysis stratified for age: <8 years (prepubertal) and 8-18 years (peri-/postpubertal). For comparison, we ran the same analyses using random-effects models. Results: Two independent assessors selected 413 out of 6158 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 <8 years had 0.18 (0.06; 0.30) nmol/L higher serum and 0.21 (0.05; 0.37) nmol/L higher salivary cortisol levels, while between 8 and 18 years, boys had 0.34 (0.28; 0.40) nmol/L lower serum and 0.42 (0.38; 0.47) nmol/L lower salivary cortisol levels. In 24-h urine, cortisol was consistently higher in boys, being 0.34 (0.05; 0.64) and 0.32 (0.17; 0.47) μg/24 h higher in the <8- and 8-18-year groups, respectively. However, gender-differences in serum cortisol <8 years and between 8 and 18 years 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 <8 years compared to girls. This pattern was reversed after the age of 8 years. In contrast, the gender-specific difference in cortisol production as assessed through 24-h 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.
KW - Glucocorticoid
KW - Infant
KW - Pediatric
KW - Sex characteristics
KW - Stress hormone
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UR - https://www.ncbi.nlm.nih.gov/pubmed/28116043
UR - http://www.scopus.com/inward/record.url?scp=85009999856&partnerID=8YFLogxK
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U2 - https://doi.org/10.1186/s13293-016-0123-5
DO - https://doi.org/10.1186/s13293-016-0123-5
M3 - Review article
C2 - 28116043
SN - 2042-6410
VL - 8
SP - 1
EP - 9
JO - Biology of Sex Differences
JF - Biology of Sex Differences
IS - 1
ER -