Venous Thromboembolism and Testosterone Therapy in Klinefelter Syndrome

Klinefelter syndrome (KS) is the most common genetic cause of male infertility, affecting approximately 1 in 660 men. It is characterized by the presence of one or more extra X chromosomes. Literature suggests an increased risk of venous thromboembolic events (VTE) in KS. Testosterone replacement therapies (TRT) are commonly used in KS to improving well-being, body composition and sexual function. However, TRT may influence the risk of VTE. Our objective was to assess the rate of VTE, and its association with TRT, in a cohort of KS patients. Data on VTE, TRT usage, and demographics were obtained from a hospital-based KS clinic database. 179 patients were included. The median age was 35 years (interquartile range [IQR] 29-42 years). 118 (66%) had received TRT prior to the review in clinic. 11 patients (6.1%) had at least one VTE. The median age of first VTE was 35 years (range 19-73 years). The incidence of a VTE was 17.0 (95% confidence interval [CI] 8.5-30.3) events per 10,000 person-years. Five of the 11 patients had received TRT prior to VTE. There was no significant association between receiving TRT and suffering a VTE (p=0.1). The incidence rate of VTE in KS patients observed here is approximately four-fold higher than in the general adult male population. This is consistent with previous studies that have showed an increase rate ratio of between 2.1 and 12.1, dependent on age. This study did not show a statistically significant difference in VTE incidence based on the use of TRT.

Publication History

Received: 03 June 2025

Accepted after revision: 16 December 2025

Accepted Manuscript online:
18 December 2025