Decreased Serum MG53 Levels Are Associated with SHBG and Androgen Excess in Women with Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by hormonal and metabolic abnormalities. Mitsugumin-53 (MG53), a multifunctional E3 ubiquitin ligase, is implicated in insulin signaling and oxidative stress regulation, yet its role in PCOS remains unclear. This study aimed to investigate serum MG53 levels in women with PCOS and explore their associations with hormonal, metabolic, and ovarian parameters. Methods: This case–control study included 64 women with PCOS and 64 healthy controls with comparable age and BMI. Serum MG53 concentrations were measured using ELISA. Hormonal, metabolic, and ultrasonographic variables were analyzed, and correlations were assessed using Spearman’s rank analysis. Independent predictors of MG53 were identified via multiple linear regression, and diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis. Results: Serum MG53 levels were significantly lower in women with PCOS compared to controls (220.8 ± 288.9 vs. 335.2 ± 392.6 pg/mL, p = 0.001). MG53 showed a positive correlation with SHBG (ρ = 0.274, p = 0.010) and negative correlations with hirsutism (ρ = –0.463, p < 0.001) and follicle count (ρ = –0.223, p = 0.034). In multivariable analysis, SHBG remained an independent positive determinant of MG53, while hirsutism and follicle count were independent negative predictors. ROC analysis indicated modest diagnostic accuracy for PCOS (AUC = 0.667, 95% CI: 0.569–0.762). Conclusions: Serum MG53 levels are reduced in PCOS and independently associated with SHBG and androgen excess, suggesting a potential link between metabolic regulation and ovarian dysfunction. Although MG53 alone has limited diagnostic value, a model combining MG53 with hormonal and metabolic parameters may improve PCOS prediction, representing a novel direction for future research. Trial registration: ClinicalTrials.gov identifier: NCT07094776.