Endocrine Abstracts

Introduction: The effects of testosterone on coagulation have not yet been clarified. In particular, it is still controversial whether male hypogonadism, or testosterone replacement therapy (TRT), may slightly increase the risk of venous thromboembolism, in particular during the first months of therapy. This study aimed to assess the hemostatic balance in hypogonadal men before and after short-term TRT, compared to healthy controls.

Methods: Thrombin generation assay (TGA) was performed in 38 hypogonadal men (10 primary hypogonadism, 19 organic central hypogonadism, 9 functional hypogonadism) before and 6 months after the initiation of TRT (transdermal testosterone gel, n = 36; long-acting i.m. testosterone undecanoate, n = 2), and in 38 age-matched healthy controls (median age 55.1 and 54.7 years respectively, P=0.91). Thrombophilia, Klinefelter syndrome, uncontrolled diabetes mellitus, anti-coagulant or anti-platelet therapy were exclusion criteria. TGA is based on the continuous registration of thrombin generation (mediated by procoagulants) and decay (mediated by anticoagulants) in platelet-poor-plasma. To make the procedure sensitive to imbalances in Factor (F)VIII–protein (P)C activities, thrombomodulin is added to the TGA assays. The following parameters are recorded: thrombin peak concentration; endogenous thrombin potential (ETP, the total amount of thrombin generated during the test); the ETP-ratio(ETP with/ETP without thrombomodulin) which accounts for FVIII-PC balance.

Results: Larger amounts of thrombin were generated in hypogonadal men at baseline (ETP 2173±288 nMxmin) and during TRT (2166±301) compared to controls (1947±273, P<0.001 and P=0.001), with no significant change over 6 months in hypogonadal patients (P=0.82). Similar results were observed when thrombomodulin was added to TGA. The ETP-ratio was comparable in hypogonadal patients before (0.68±0.23) and after TRT (0.68±0.20, P=0.73), and in controls (0.61±0.20, P=0.17 and P=0.13). Thrombin peak did not change from baseline to six months (P=0.29); however, it was significantly higher than controls only at baseline (P=0.03). ETP was inversely associated with total testosterone concentrations at baseline (r=-0.44, P=0.008) but not when on TRT.

Conclusion: A procoagulant imbalance is observed in hypogonadal men. This does not appear to involve the FVIII-PC axis and is not modified by short term testosterone therapy. Further studies are needed to clarify which coagulation factors drive the procoagulant imbalance, whether longer TRT can normalize it, and if platelets or endothelial cells are affected as well.