Global Fibrinolytic Capacity Is Decreased in Polycystic Ovary Syndrome, Suggesting a Prothrombotic State

Abstract

The polycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular disease (CVD). Insulin resistance (IR), hyperandrogenism, and dyslipidemia are well-known cardiovascular risk factors in PCOS. Impaired fibrinolysis could also contribute to the development of CVD in PCOS. Global fibrinolytic capacity (GFC) is a recently developed method, which is reflected by the amount of generated D-dimer when the fibrinolysis of a freeze-dried fibrin clot is stopped by introducing aprotinin. GFC is sensitive to all the factors involved in the process of fibrinolysis. We evaluated whether women with PCOS have any alterations in the GFC and other essential hemostatic parameters. Fifty-nine nonobese, normal glucose-tolerant women with PCOS (age, 22.9 ± 4.4 yr; body mass index, 23.0 ± 2.4 kg/m2 ) and 23 age- and body mass index-matched healthy controls participated. We measured GFC and triglycerides; total cholesterol; HDL-cholesterol (HDL-C); lipoprotein-a; prothrombin time; partial thromboplastin time; thrombin time; antithrombin III; factors II, V, VII, and X; fibrinogen; plasminogen; antiplasmin; and D-dimer. Serum glucose and insulin (at baseline and during a 75-g 2-h oral glucose tolerance test) were also measured, and IR was assessed by homeostatic model assessment. GFC was significantly lower in the PCOS group, compared with the control group (2.49 ± 1.6 vs. 5.95 ± 2.43 μg/ml, P < 0.001). All the other coagulation and fibrinolysis parameters were comparable between the two groups. The PCOS group had lower HDL-C and higher IR values. GFC was correlated with testosterone and free testosterone negatively and with HDL-C positively. There was no correlation between GFC and any of the IR parameters. Our results suggest that women with PCOS have impaired fibrinolysis, as reflected by the decreased GFC. This impairment is not related to the IR and may increase the risk of CVD in PCOS.