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

No changes in thrombin generation assay (TGA) parameters were observed in hypogonadal men after 6 months of testosterone replacement therapy.

• TGA parameters assessed included lag time, thrombin-peak concentration, time-to-reach peak, velocity index, and endogenous thrombin potential (ETP).
• Measurements were taken at baseline (T0) and 6 months after starting TRT (T1).
• The study included 38 men with hypogonadism with a mean age of 55 years (SD 13).
• Protein C, antithrombin, factor VIII, and fibrinogen were also assessed and showed no significant changes after TRT.

Hypogonadal men displayed significantly higher endogenous thrombin potential (ETP) compared to healthy controls both before and after testosterone replacement therapy.

• ETP represents the total amount of thrombin generated under the driving forces of procoagulants opposed by anticoagulants.
• The difference in ETP between hypogonadal men and healthy controls was present at both T0 and T1.
• 38 age-matched healthy controls (HCs) were used for comparison.
• ETP was correlated with testosterone levels.

Hypogonadal men had significantly higher fibrinogen levels than healthy controls at both T0 and T1.

• Elevated fibrinogen persisted both before and after 6 months of testosterone replacement therapy.
• Fibrinogen was one of several coagulation markers assessed alongside TGA parameters.
• This finding contributed to characterization of hypogonadism as a procoagulant state.

Hypogonadal men had significantly lower antithrombin levels compared to healthy controls at both T0 and T1.

• Antithrombin is an anticoagulant factor, and its reduction contributes to a procoagulant imbalance.
• Lower antithrombin levels persisted both before and after 6 months of TRT.
• Antithrombin was correlated with testosterone levels, suggesting a relationship between hypogonadism and anticoagulant activity.

Thrombin peak was significantly higher in hypogonadal men compared to healthy controls at baseline but not after 6 months of testosterone replacement therapy.

• At T0, hypogonadal men had a significantly higher thrombin peak than HCs.
• At T1 (6 months post-TRT), thrombin peak in hypogonadal men was no longer significantly different from HCs.
• This was the one TGA parameter showing a differential pattern between T0 and T1 relative to controls.

Both ETP and antithrombin were correlated with testosterone levels in hypogonadal men.

• ETP showed a correlation with testosterone levels, suggesting that the degree of androgen deficiency relates to the magnitude of procoagulant activity.
• Antithrombin also correlated with testosterone levels, linking androgen status to anticoagulant capacity.
• These correlations support a mechanistic link between hypogonadism and the observed procoagulant imbalance.

Hypogonadal men as a group displayed a procoagulant imbalance characterized by increased thrombin generation compared to healthy controls.

• The procoagulant imbalance was evidenced by higher ETP, higher fibrinogen, higher thrombin peak (at baseline), and lower antithrombin.
• The study was conducted at 2 tertiary endocrinological ambulatory care centers using an observational prospective cohort design.
• The thrombin generation assay is described as 'an in vitro procedure based on the continuous registration of thrombin generation and decay under conditions mimicking the process that occurs in vivo.'