Testosterone treatment and association with thrombin generation and coagulation inhibition in Klinefelter syndrome: A cross-sectional study

Abstract Background The background for the increased occurrence of thrombosis seen in Klinefelter syndrome (KS) is unknown. The aim was to compare thrombin generation and coagulation inhibition between men with KS and controls, and to investigate whether coagulation in KS was associated with testosterone treatment (TT), and as such, measures of androgen action. Methods Untreated men with KS (U-KS) or testosterone treated men with KS (T-KS) were included. KS groups were matched by age and education to groups of control males with no history of TT. Blood samples were collected after overnight fasting. Low tissue factor (1pM) thrombin generation was expressed as lag time (min), time to peak (min), peak (nmol/L), and endogenous thrombin potential (nmol/L × min, ETP). Coagulation inhibitors, sex hormones, and haematocrit were measured. Matched groups were compared by Student's t-test or Wilcoxon rank sum test. Among KS, TT status as an outcome predictor was evaluated by linear regression. Results 18 U-KS and 27 T-KS with corresponding controls participated. Thrombin generation was not different comparing U-KS and T-KS with respective control groups. Among KS, ETP was lower in T-KS compared with U-KS and inversely associated with testosterone, LH-testosterone ratio and haematocrit. Conclusion Neither U-KS nor T-KS expressed a pro-coagulant state compared with controls. Thrombin generation among KS was inversely associated with androgen action and lower in T-KS compared with U-KS. Whether TT is capable of lowering thrombotic risk among men with KS needs to be assessed prospectively.