Gender-specific differences in hypothalamus-pituitary-adrenal axis activity during childhood: a systematic review and meta-analysis

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Abstract

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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalBiology of Sex Differences
Volume8
Issue number1
DOIs
Publication statusPublished - 19 Jan 2017

Cite this

@article{4acef2695f49483f937c07b4dc51ae48,
title = "Gender-specific differences in hypothalamus-pituitary-adrenal axis activity during childhood: a systematic review and meta-analysis",
abstract = "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.",
keywords = "Glucocorticoid, Infant, Pediatric, Sex characteristics, Stress hormone",
author = "{Van der Voorn}, Bibian and Hollanders, {Jonneke J.} and Ket, {Johannes C.F.} and Joost Rotteveel and Finken, {Martijn J.J.}",
year = "2017",
month = "1",
day = "19",
doi = "10.1186/s13293-016-0123-5",
language = "English",
volume = "8",
pages = "1--9",
journal = "Biology of Sex Differences",
issn = "2042-6410",
publisher = "BioMed Central Ltd.",
number = "1",

}

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.

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

UR - http://www.scopus.com/inward/record.url?scp=85009999856&partnerID=8YFLogxK

U2 - 10.1186/s13293-016-0123-5

DO - 10.1186/s13293-016-0123-5

M3 - Review article

VL - 8

SP - 1

EP - 9

JO - Biology of Sex Differences

JF - Biology of Sex Differences

SN - 2042-6410

IS - 1

ER -