Effects of metformin therapy on markers of coagulation disorders in hyperinsulinemic women with polycystic ovary syndrome

Abstract

Objectives: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and oligo-/anovulation and is associated with risk factors for cardiovascular disorders, such as insulin resistance and central adiposity. All these factors can lead to endothelial dysfunction and impaired coagulation processes. Metformin effectively treats hyperinsulinemia in women with PCOS. However, clinical trials assessing influence of metformin on endothelium and fibrinolysis are limited. Therefore, the objective of this study was to prospectively assess the effects of a 6-month metformin therapy on body mass index (BMI), insulin sensitivity and coagulation/fibrinolysis markers in hyperinsulinemic women with PCOS. Materials and Methods: Thirty hyperinsulinemic PCOS women (aged 26.0±3.7 [mean ±SD]) without any additional disorders were included into the study. Metformin was administered at a dose of 1700 mg daily for 6 months. Serum plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) concentrations and von Willebrand factor (vWf) levels were measured with specific assays, together with glucose and insulin concentrations. Insulin sensitivity index (ISI) and BMI were calculated. Results: All patients completed the study and no side effects were reported. BMI decreased significantly (by 8.5%, p<0.0001). The metformin therapy improved insulin sensitivity, as evidenced by an increase in ISI by 41.5% (p=0.0005). A marked reduction in PAI-1 (by 26%, p<0.005) concentrations was observed. No significant changes were noted for t-PA and vWf. Conclusions: Metformin administration decreases the circulating PAI-1 concentration and simultaneously improves insulin sensitivity and BMI in PCOS women with hyperinsulinemia. Long-term metformin administration may be a new prophylactic measure for the prevention of cardiovascular disorders in such patients.