Serum Sortilin Levels as a Metabolic Biomarker in Polycystic Ovary Syndrome: A Case-Control Study from Southern Iraq

Abstract

Background: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine-metabolic disorder affecting women of reproductive age, characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. Emerging evidence suggests that sortilin, a VPS10-domain receptor protein involved in lipid metabolism and insulin signaling, may play a role in PCOS pathophysiology through its association with metabolic dysregulation. Objective: This study aimed to assess serum sortilin levels in women with PCOS compared to healthy controls and to examine the association between sortilin and metabolic-hormonal parameters, including insulin resistance, testosterone levels, and body mass index (BMI). Methodology: A case-control study was conducted involving 120 female participants (60 PCOS patients and 60 healthy controls, aged 18–45 years) recruited from Basra Women and Children Teaching Hospital between September 2025 and January 2026. PCOS diagnosis was established using the Rotterdam criteria. Serum sortilin and biochemical markers were quantified using ELISA and automated analyzers.  Results: Serum sortilin levels were significantly elevated in PCOS patients compared to controls (4.57 ± 0.98 vs. 2.56 ± 0.86 ng/mL, p < 0.001). A significant association was observed between sortilin and insulin resistance (p = 0.042), but not with BMI (p = 0.558). ROC analysis demonstrated excellent diagnostic performance (AUC = 0.943; sensitivity = 85%; specificity = 86.7%; cut-off = 3.650 ng/mL). Conclusion: Elevated serum sortilin may serve as a promising metabolic biomarker for PCOS, particularly reflecting insulin resistance rather than anthropometric measures. These findings suggest sortilin's potential utility in identifying metabolic dysfunction in PCOS and warrant further validation in larger, multicenter cohorts.