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Leptin and LH/FSH Ratio as Independent Predictors of Polycystic Ovary Syndrome in Normoglycemic Women: A Case-Control Study

Singh, J.; Jain, A.

2025-09-12 obstetrics and gynecology
10.1101/2025.09.11.25335551 medRxiv
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BACKGROUNDPolycystic ovary syndrome (PCOS) is a multifaceted disorder characterized by reproductive, metabolic, and endocrine disturbances. While insulin resistance (IR) is recognized as a central feature, the interplay of adipokines, lipid metabolism, gonadotropin imbalance, and inflammation in normoglycemic PCOS women remains underexplored. METHODSA case-control study was conducted on 30 newly diagnosed normoglycemic women with PCOS (Rotterdam criteria, 2003) and 30 age-matched healthy controls. Anthropometric, hormonal (LH, FSH, LH/FSH ratio, prolactin, estrogen, progesterone, testosterone), metabolic (fasting glucose, HbA1c, insulin, HOMA-IR), lipid (cholesterol, triglycerides, HDL), adipokine (leptin), and hematological parameters were assessed. Group comparisons were performed using independent t-test/Mann-Whitney test as appropriate. Correlation analysis explored inter-relationships among variables, and multivariate logistic regression identified independent predictors of PCOS. RESULTSCompared with controls, PCOS women had significantly higher BMI (26.3 +/- 5.3 vs. 23.4 +/- 3.2 kg/m2; p=0.014), WHR (0.861 +/- 0.061 vs. 0.799 +/- 0.060; p<0.001), LH (7.5 +/- 3.7 vs. 5.3 +/- 2.2 mIU/mL; p=0.006), LH/FSH ratio (1.37 +/- 0.76 vs. 0.76 +/- 0.32; p<0.001), estrogen (54.5 +/- 18.2 vs. 38.0 +/- 11.1 pg/mL; p<0.001), testosterone (49.7 +/- 25.1 vs. 34.5 +/- 14.0 ng/dL; p=0.001), fasting insulin (11.55 +/- 10.8 vs. 5.63 +/- 2.6 uIU/mL; p=0.004), HOMA-IR (2.47 +/- 2.4 vs. 1.17 +/- 0.54; p=0.007), and leptin (31.3 +/- 17.4 vs. 16.4 +/- 10.5 ng/mL; p<0.001), with significantly lower FSH (5.6 +/- 1.7 vs. 7.2 +/- 1.9 mIU/mL; p<0.001) and HDL (43.0 +/- 10.0 vs. 54.3 +/- 15.3 mg/dL; p<0.001). Correlation analysis revealed positive associations between BMI and leptin, insulin, and HOMA-IR; WHR and testosterone; TLC and leptin/WHR; and LH/FSH ratio and estrogen, while HDL correlated negatively with HOMA-IR and TLC. Logistic regression identified leptin (OR = 1.105, 95% CI 1.016-1.201, p=0.020) and LH/FSH ratio (OR = 18.48, 95% CI 1.82-187.7, p=0.014) as independent predictors of PCOS. CONCLUSIONNormoglycemic PCOS women show distinct hormonal, metabolic, and adipokine alterations, with leptin and LH/FSH emerging as robust independent predictors. These findings highlight the early convergence of adiposity, insulin resistance, inflammation, and gonadotropin imbalance in PCOS, underscoring the need for early biomarker-based risk stratification and intervention even before the onset of overt glycemic abnormalities.

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