EBioMedicine · 2026
Serum biomarkers for the diagnosis and management of adolescent polyendocrine metabolic ovarian syndrome: a systematic review and meta-analysis.
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Shi Yue, Wang Chi Chiu, Stener-Victorin Elisabet, Chung Pui Wah, Wang Yao
Аннотация
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, CUHK 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.
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, CUHK 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.