Testosterone Therapy Does Not Affect Coagulation in Male Hypogonadism: A Longitudinal Study Based on Thrombin Generation

Abstract Context Testosterone therapy has been variably associated with increased thrombotic risk but investigations of global coagulation in this setting are lacking. Objective This work aimed to compare global coagulation of hypogonadal men before (T0) and 6 months after (T1) starting testosterone replacement therapy (TRT), and healthy controls (HCs). Methods An observational prospective cohort study was conducted at 2 tertiary endocrinological ambulatory care centers. Patients included 38 men with hypogonadism (mean age 55 years, SD 13) and 38 age-matched HCs. Thrombin generation assay (TGA) was performed at T0 and T1 in hypogonadal men and in HCs. TGA is an in vitro procedure based on the continuous registration of thrombin generation and decay under conditions mimicking the process that occurs in vivo. The following TGA parameters were recorded: lag time; thrombin-peak concentration; time-to-reach peak, velocity index, and endogenous thrombin potential (ETP), the latter representing the total amount of thrombin generated under the driving forces of procoagulants opposed by the anticoagulants. Protein C, antithrombin, factor (F) VIII, and fibrinogen were assessed. Results No changes in TGA parameters were observed between T0 and T1. Hypogonadal men displayed significantly higher ETP, fibrinogen, and significantly lower antithrombin levels both at T0 and T1 compared to HCs. Thrombin peak of hypogonadal men was significantly higher than HCs at T0 but not at T1. ETP and antithrombin were correlated with testosterone levels. Conclusion Hypogonadal men display a procoagulant imbalance detected by increased thrombin generation. Short-term TRT does not worsen global coagulation, suggesting that the treatment can be safely prescribed to men diagnosed with hypogonadism.