Association Between Renin-Angiotensin System Peptides and Inflammatory Cytokines in Polycystic Ovary Syndrome

Background & Objective: Polycystic Ovary Syndrome (PCOS) involves chronic inflammation and alterations in the Renin-Angiotensin System (RAS). This study was conducted with aim to examine the relationship between key RAS peptides and pro-inflammatory cytokines in PCOS. Materials & Methods: This case-control study was conducted between December 2024 and March 2025 at Fallujah Teaching Hospital for Women and Children, in Fallujah, Anbar, Iraq. Ninety reproductive-aged women (18-40 years) were enrolled, including 45 newly diagnosed PCOS patients and 45 healthy controls. Anthropometric, metabolic, and reproductive parameters were evaluated. Serum levels of Angiotensin II, Angiotensin (1-7), IL-6, and TNF-α were measured. Data were analyzed using IBM SPSS Statistics (version 27.0) and independent t-test or Mann–Whitney U test, ANCOVA, Spearman correlation, ROC analysis, and regression model. P<0.05 was considered statistically significant. Results: Pro-inflammatory cytokines were elevated in the PCOS group (serum concentrations of IL-6 (8.2 vs 4.1 pg/mL, P=0.013) and TNF-α (8.0 vs 1.7 pg/mL, P=0.039), whereas Ang (1-7) levels were lower (18.1 vs 21.2 pg/mL, P<0.01) compared with controls); however, after BMI adjustment, IL-6 became borderline and TNF-α lost statistical significance. Correlation analysis revealed LH and FSH were moderately correlated with TNF-α (r=0.479 and r=0.464, respectively; both P=0.001). ROC analysis identified AMH as the strongest discriminator for PCOS (AUC=0.866), followed by total testosterone (AUC=0.765), while Angiotensin (1-7) showed moderate diagnostic accuracy with an inverse relationship (AUC=0.718). Conclusion: This study identified alterations RAS in women with PCOS, evidenced by lower Ang (1-7) levels, along with associations between inflammatory markers and reproductive hormones. Further prospective studies are required to confirm these findings.