Premature adrenarche and metabolic risk: a systematic review and meta-analysis
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Objective
Premature adrenarche (PA), characterised by pre-pubertal adrenal androgen excess and hyperandrogenic symptoms, is considered a forerunner of polycystic ovary syndrome, which comes with increased metabolic risk. Here, we aimed to systematically evaluate the evidence on surrogate parameters of metabolic risk in children with PA.
Methods
We searched major databases (1990-March 2025) for studies on PA in children analysing body composition and markers of glucose and lipid metabolism. Two reviewers independently selected studies, collected data, and appraised study quality. Results were standardised, tabulated, and pooled for meta-analysis.
Results
Twenty-five case-control studies reported on 694 children with PA and 567 healthy controls (boys and girls). Height standard deviation score (SDS), weight SDS, and body mass index SDS were significantly higher in PA than in controls. Children with PA also presented with higher fasting insulin (FI) levels than controls (MD: 15.04, 95% CI: 5.27-24.81 pmol/L; I2 = 91%). These findings persisted after sensitivity analysis for gender and risk of bias assessment. Other markers of metabolic risk, such as fasting glucose, HOMA-IR, mean serum glucose and insulin during the oral glucose tolerance test, and fasting lipids, did not differ between children with PA and controls.
Conclusions
Children with PA are taller, heavier, and have higher FI levels than their healthy peers at presentation. We observed significant heterogeneity of reported outcomes with generally small participant numbers in the included studies. Large-scale studies with comprehensive, unified assessment and long-term follow-up are needed to explore the extent of metabolic dysfunction that may develop over time.
Premature adrenarche (PA), characterised by pre-pubertal adrenal androgen excess and hyperandrogenic symptoms, is considered a forerunner of polycystic ovary syndrome, which comes with increased metabolic risk. Here, we aimed to systematically evaluate the evidence on surrogate parameters of metabolic risk in children with PA.
Methods
We searched major databases (1990-March 2025) for studies on PA in children analysing body composition and markers of glucose and lipid metabolism. Two reviewers independently selected studies, collected data, and appraised study quality. Results were standardised, tabulated, and pooled for meta-analysis.
Results
Twenty-five case-control studies reported on 694 children with PA and 567 healthy controls (boys and girls). Height standard deviation score (SDS), weight SDS, and body mass index SDS were significantly higher in PA than in controls. Children with PA also presented with higher fasting insulin (FI) levels than controls (MD: 15.04, 95% CI: 5.27-24.81 pmol/L; I2 = 91%). These findings persisted after sensitivity analysis for gender and risk of bias assessment. Other markers of metabolic risk, such as fasting glucose, HOMA-IR, mean serum glucose and insulin during the oral glucose tolerance test, and fasting lipids, did not differ between children with PA and controls.
Conclusions
Children with PA are taller, heavier, and have higher FI levels than their healthy peers at presentation. We observed significant heterogeneity of reported outcomes with generally small participant numbers in the included studies. Large-scale studies with comprehensive, unified assessment and long-term follow-up are needed to explore the extent of metabolic dysfunction that may develop over time.
Date Issued
2025-09-01
Date Acceptance
2025-08-12
Citation
European Journal of Endocrinology (EJE), 2025, 193 (3), pp.S1-S14
ISSN
0804-4643
Publisher
Oxford University Press
Start Page
S1
End Page
S14
Journal / Book Title
European Journal of Endocrinology (EJE)
Volume
193
Issue
3
Copyright Statement
© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40884153
PII: 8244424
Subjects
ADIPOSITY
androgen excess
ANDROGENS
CARDIOVASCULAR RISK
CHILDREN
dyslipidaemia
Endocrinology & Metabolism
FAT
HISTORY
HYPERINSULINEMIA
insulin resistance
INSULIN SENSITIVITY
Life Sciences & Biomedicine
obesity
PRECOCIOUS PUBARCHE
PREPUBERTAL GIRLS
pubarche
puberty
Science & Technology
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2025-08-30