Systemic redox imbalance and metabolic reprogramming in polycystic ovary syndrome: an integrated biomarker analysis

Background Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder in which oxidative stress is closely implicated in pathophysiology. The integration of dynamic thiol/disulfide homeostasis, advanced oxidation protein products (AOPP), total antioxidant capacity (TAC), and metabolic markers (serum citrate and lactate dehydrogenase) has not been explored in a single PCOS cohort. Objective To evaluate systemic redox status and associated metabolic markers in women with PCOS by measuring thiol/disulfide homeostasis, AOPP, malondialdehyde (MDA), TAC, serum citrate, and lactate dehydrogenase (LDH). Methods We conducted a case-control study that enrolled 100 women: 50 with Rotterdam-defined PCOS and 50 age-matched healthy controls (the two groups were not matched for body mass index; see below). Spectrophotometric assays quantified serum native thiol, total thiol, disulfide, AOPP, MDA, TAC, citrate, and LDH activity. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis, and group differences were re-examined after adjustment for BMI using analysis of covariance. Results PCOS patients exhibited significantly depleted native and total thiols, along with elevated disulfide, AOPP, and MDA levels, and reduced TAC and serum citrate ( p < 0.001). LDH activity was markedly higher in the PCOS group ( p < 0.001). All between-group differences remained significant after adjustment for BMI. ROC analysis highlighted native thiol (AUC = 0.865) and LDH (AUC = 0.850) as the strongest single markers. A multivariable logistic model combining these biomarkers discriminated PCOS with high accuracy (apparent AUC = 0.99; 10-fold cross-validated AUC = 0.99; bootstrap optimism-corrected AUC = 0.98). Conclusion PCOS is characterized by a coordinated redox imbalance accompanied by a metabolic shift toward anaerobic glycolysis consistent with mitochondrial inefficiency. Integrating these biomarkers into evaluation may refine diagnostic precision and support hypothesis-generating work on antioxidant-targeted strategies.