Premature adrenarche and metabolic risk: a systematic review and meta-analysis

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.