Comprehensive Assessment of the Hemostatic System in Polycystic Ovarian Syndrome

Abstract

Polycystic ovarian syndrome (PCOS) affects 12 to 19% of women and has reproductive and metabolic features (endothelial dysfunction, increased diabetes, and cardiovascular risk factors). It also appears to have altered coagulation and fibrinolysis with a prothrombotic state with epidemiological evidence of increased venous thromboembolism. We aimed to comprehensively assess hemostasis in women with PCOS versus control women. In an established case-control cohort of lean, overweight, and obese women with (n = 107) and without PCOS (n = 67), with existing measures of plasminogen activator inhibitor 1 (PAI-1), asymmetric dimethylarginine (ADMA), hormonal, and metabolic markers, we also assessed prothrombin fragments 1 and 2 (PF1 & 2), plasminogen, tissue plasminogen activator (tPA), and thrombin generation (TG). Higher levels of ADMA (0.70 vs. 0.39 µmol/L, p < 0.01), PAI-1 (4.80 vs. 3.66 U/mL, p < 0.01), and plasminogen (118.39 vs. 108.46%, p < 0.01) were seen in PCOS versus controls, and persisted after adjustment for age and body mass index (BMI). PF1 & 2 was marginally lower (180.0 vs. 236.0 pmol/L, p = 0.05), whereas tPA and TG were not different between groups, after adjustment for age and BMI. Significant relationships were observed between hormonal and metabolic factors with ADMA and PAI-1. We demonstrate impaired fibrinolysis in PCOS. In the context of abnormal endothelial function and known hormonal and metabolic abnormalities, this finding may underpin an increased risk of cardiovascular disease and venous thrombosis in PCOS.

Liraglutide in polycystic ovary syndrome: a randomized trial, investigating effects on thrombogenic potential

“…Moreover, high thrombin generation is associated with first and recurrent VTE and possibly with coronary atherosclerosis (13, 14, 15). Thrombin generation has been found to be elevated in PCOS (12), but conflicting data exist (16). In a previous study, our group found high thrombin generation, PAI-1 and hsCRP to be linked to the overweight and insulin-resistant PCOS phenotype (17, 18).…”

Cardiometabolic Risks in Polycystic Ovary Syndrome: Non-Traditional Risk Factors and the Impact of Obesity

“…Oral contraceptive pills may increase cardiovascular disease and increase the risk of venous thromboembolism [3,119] . A recent study by Burchall et al [120] reported impaired fibrinolysis (elevated plasminogen activator inhibitor-1 and plasminogen) in women with PCOS versus controls, even after adjustment for age and BMI. This was exacerbated by oral contraceptive pill treatment.…”

“…Women with PCOS have a significantly higher risk of venous thromboembolism compared with non-affected women [119] . These risks are exacerbated by oral contraceptive pill use, a common PCOS management strategy, targeting reproductive features including menstrual cycle regulation and hirsutism [120] . Oral contraceptive pills may increase cardiovascular disease and increase the risk of venous thromboembolism [3,119] .…”

Lean Women with Polycystic Ovary Syndrome

“…Some possible reasons for increased plasma fibrinogen are: increased inflammatory processes [64], decreased fibrinolysis [65], and as an acute phase reactant. Enhancement in fibrinogen level stimulates RBC aggregation and significantly increased resistance in blood flow [66].…”