Association of serum GDF15 levels with polycystic ovary syndrome and metformin therapy: A cross-sectional study

Objective: To evaluate serum Growth Differentiation Factor 15 (GDF15) levels in women with polycystic ovary syndrome (PCOS) and to assess the association between metformin therapy and GDF15 concentrations. Methods: This cross‑sectional study included 130 participants: 40 healthy controls, 45 PCOS patients not receiving metformin, and 45 PCOS patients receiving metformin for at least six months. Serum levels of fasting blood glucose, insulin, luteinizing hormone (LH), follicle‑stimulating hormone (FSH), testosterone, and GDF15 were measured. Insulin resistance was estimated using the homeostatic model assessment (HOMA‑IR). Group comparisons were performed using one‑way ANOVA with post‑hoc tests. Results: GDF15 levels were significantly different across groups (F=39.408, p<0.001). Post‑hoc analysis showed that PCOS patients not on metformin had higher GDF15 levels (889±189 pg/mL) than healthy controls (690±125 pg/mL, p=0.003). Notably, PCOS patients on metformin showed the highest GDF15 levels (984±152 pg/mL), significantly higher than both untreated PCOS patients (p<0.05) and controls (p<0.001). HOMA‑IR, fasting glucose, insulin, and testosterone were also significantly elevated in PCOS groups compared with controls (all p<0.001). Conclusion: Serum GDF15 levels are elevated in PCOS and are further elevated in association with metformin therapy. GDF15 may serve as a marker of metabolic stress in PCOS and a potential indicator of metformin exposure or response. Longitudinal studies are needed to establish causality.