Manar Khalid Ibrahim and I Masryia Rashad Hassein
Background: Polycystic Ovary Syndrome (PCOS) is a multifactorial endocrine disorder affecting 15-20% of reproductive-aged women worldwide. It is characterized by a heterogeneous constellation of clinical, hormonal, and metabolic abnormalities, including hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. While its etiology is considered polygenic and influenced by environmental factors, the disorder also shows strong familial aggregation. Recent evidence suggests that cystatin C, a cysteine protease inhibitor and emerging biomarker of cardiovascular and metabolic risk, may be elevated in PCOS independent of renal function.
Objective: This study aimed to evaluate the role of serum cystatin C as a predictive marker of metabolic and cardiovascular disturbances in adolescent females with PCOS.
Methods: A cross-sectional case-control study was conducted at Tikrit Teaching Hospital from October 2024 to June 2025, including 60 adolescent girls with PCOS diagnosed using the Rotterdam criteria and 60 age-matched healthy controls. Detailed clinical, anthropometric, biochemical, hormonal, and ultrasonographic evaluations were performed. Serum cystatin C was measured using ELISA. Insulin resistance was assessed by HOMA-IR, and lipid profile parameters were analyzed. Statistical analysis included correlation testing, ROC curve analysis, and multivariate logistic regression.
Results: Adolescents with PCOS demonstrated significantly higher BMI, blood pressure, hirsutism, menstrual irregularities, and acne compared to controls (p<0.001). Biochemically, PCOS participants exhibited elevated fasting glucose, insulin, HOMA-IR, total cholesterol, triglycerides, LDL, and testosterone, with significantly lower HDL levels (p<0.001). Serum cystatin C levels were markedly higher in the PCOS group (1.34±0.29 ng/mL) than in controls (1.02±0.21 ng/mL, p<0.001). Cystatin C positively correlated with BMI (r=0.46), HOMA-IR (r=0.58), total cholesterol, triglycerides, and LDL, and negatively with HDL. ROC analysis revealed an AUC of 0.812, indicating good diagnostic performance (sensitivity 81.7%, specificity 76.3%, cut-off 1.12 ng/mL). Multivariate regression identified cystatin C (OR: 2.91, 95% CI: 1.74-5.47), along with BMI, HOMA-IR, and testosterone, as an independent predictor of PCOS.
Conclusion: Serum cystatin C levels are significantly elevated in adolescents with PCOS and are closely associated with insulin resistance and dyslipidemia. Cystatin C shows promise as a non-invasive early biomarker for identifying adolescents at risk of metabolic and cardiovascular complications in the context of PCOS.
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