Serum biomarkers for the diagnosis and management of adolescent polyendocrine metabolic ovarian syndrome: a systematic review and meta-analysis

Abstract

Summary Background Adolescent polyendocrine metabolic ovarian syndrome (PMOS) poses immediate and lifelong risks to women’s health. However, reliable biomarkers for adolescent PMOS remain elusive in current clinical practice. Methods We systematically searched six databases from inception to April 2026, following PRISMA guidelines (PROSPERO No.: CRD420251033057). Eligible studies included adolescents with PMOS and healthy controls. Primary outcomes were effect sizes of serum reproductive hormones, insulin indices, and adipokines (Hedges’ g in random-effects models), with diagnostic performance assessed by AUC, sensitivity, and specificity. Findings Fifty-one moderate-to-high quality studies comprising 4892 adolescents were included. Large effect sizes were observed for total testosterone (TT, 1.10), free androgen index (FAI, 1.19), ratio of luteinising hormone to follicle-stimulating hormone (LH/FSH, 1.07), anti-Müllerian hormone (AMH, 0.98), and adiponectin (-1.12), all with moderate-to-low certainty. Insulin resistance indices (homoeostatic model assessment of insulin resistance [HOMA-IR], 0.64; quantitative insulin sensitivity check index [QUICKI], -0.47) and leptin (0.40) showed small effect sizes with low certainty. In adolescents with obesity, AMH (1.39) and adiponectin (-1.54) showed pronounced effects. For diagnostic performance, TT (cutoff = 55.96 ng/dL), FAI (cutoff = 6.78), and LH/FSH (cutoff = 1.59) each achieved an AUC of 0.74. AMH effectively identified PMOS in obese group (AUC = 0.85, cutoff = 4.47 ng/mL) and the <17-year-old group (AUC = 0.77, cufoff = 6.05 ng/mL). For metabolic stratification, HOMA-IR performed modestly overall AUC of 0.65 (cutoff = 4.35), while adiponectin (AUC = 0.78, cutoff = 10.92 μg/mL) and leptin (AUC = 0.67, cutoff = 36.17 ng/mL) emerged as BMI-dependent markers in obese and non-obese groups, respectively. Of note, LH/FSH and dehydroepiandrosterone sulphate (DHEAS) showed significant publication bias; thus, these results should be interpreted with caution. Interpretation TT and FAI are primary diagnostic biomarkers in adolescent PMOS, with LH/FSH providing supportive value. AMH is discriminative in adolescents with obesity in early-mid adolescence. HOMA-IR is a primary biomarker for metabolic monitoring, while adiponectin and leptin are BMI-dependent markers for early metabolic risk stratification. Funding This study was supported by HMRF, 10.13039/501100004853CUHK direct grant, CUHK-Chulalongkorn University Research Fund, 1 + 1 + 1 CUHK-CUHK(SZ)-GDST Joint Collaboration Fund, and PhD International Mobility for Partnerships and Collaboration Award.