Metabolic and hormonal correlates of leptin, uric acid and soluble neprilysin in polycystic ovary syndrome/ Polyendocrine Metabolic Ovarian Syndrome.

Abstract

Background: Polycystic ovary syndrome (PCOS) / Polyendocrine Metabolic Ovarian Syndrome (PMOS) is a complex endocrine and metabolic disorder in women of reproductive age. This study aimed to evaluate the relationship between serum leptin, uric acid and soluble neprilysin levels and metabolic and hormonal parameters in women with PCOS/PMOS. The evaluation of new metabolic biomarkers in conjunction with hormonal parameters may contribute to a better understanding of the metabolic aspects and pathophysiology of PCOS/PMOS.

Materials and methods: This case-control study was conducted on 90 women, including 60 patients diagnosed with PCOS/PMOS and 30 healthy age-matched controls. The PCOS/PMOS group was further divided into obese and non-obese subgroups according to body mass index (BMI). Demographic characteristics, Ferriman-Gallwey (FG) scores, anthropometric measurements, hormonal profiles (anti-Müllerian hormone (AMH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, progesterone, prolactin, estradiol), and metabolic parameters (fasting blood glucose, insulin, triglycerides, uric acid) were recorded. Venous blood samples were collected after an 8-12-hour fast during the early follicular phase of the menstrual cycle. Serum leptin and soluble neprilysin levels were measured using the ELISA method. Group comparisons, post-hoc analyses, correlation analysis, ROC analysis, age- and BMI-adjusted ANCOVA, and penalized LASSO logistic regression were performed to evaluate biomarker associations and discriminatory performance for PCOS/PMOS.

Results: LH, AMH, testosterone, HOMA-IR, triglycerides, uric acid, and leptin levels were significantly higher in the PCOS/PMOS group than in controls, with the most pronounced metabolic abnormalities observed in the obese PCOS/PMOS subgroup. Leptin levels were highest in obese women with PCOS/PMOS (p < 0.001), whereas soluble neprilysin levels did not differ significantly among groups (p = 0.233). Correlation analyses showed that leptin was strongly associated with adiposity and insulin-resistance-related parameters, including BMI, HOMA-IR, and uric acid. ROC analysis demonstrated strong discriminatory performance for waist-to-height ratio (AUC = 0.899), testosterone (AUC = 0.895), waist-to-hip ratio (AUC = 0.891), and AMH (AUC = 0.882), while HOMA-IR, leptin, and TyG index showed acceptable discriminatory ability. After adjustment for age and BMI, only TyG index and WHR remained significantly different among groups, whereas leptin and soluble neprilysin did not. LASSO logistic regression retained AMH, testosterone, WHR, and log-transformed leptin in a parsimonious classification model, indicating that hormonal markers and central adiposity indices contributed most consistently to PCOS/PMOS classification, while the independent contribution of leptin appeared limited by its close association with adiposity.

Conclusion: Collectively, these findings indicate that the metabolic phenotype of PCOS/PMOS is driven primarily by obesity, central adiposity, and insulin-resistance-related disturbances rather than by leptin or soluble neprilysin as independent disease-specific biomarkers. Central adiposity indices and insulin-resistance-related markers, particularly WHR and TyG index, may therefore provide useful metabolic information in PCOS/PMOS assessment. Leptin appears to reflect adiposity-related metabolic burden, while soluble neprilysin did not show diagnostic or independent adjusted discriminatory value in this cohort.

Clinical trial number: Not applicable.