Venous Thromboembolism and Testosterone Therapy in Klinefelter Syndrome

Abstract

Klinefelter syndrome 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 studies suggest an increased risk of venous thromboembolic events in Klinefelter syndrome. Testosterone replacement therapies are commonly used in Klinefelter syndrome to improve well-being, body composition and sexual function. However, testosterone replacement therapies may influence the risk of venous thromboembolic events. Our objective was to assess the rate of venous thromboembolic events, and its association with testosterone replacement therapies, in a cohort of Klinefelter syndrome patients. Data on venous thromboembolic events, testosterone replacement therapy usage, and demographics were obtained from a hospital-based Klinefelter syndrome clinical database. One hundred seventy-nine patients were included. The median age was 35 years (interquartile range: 29–42 y). One hundred eighteen patients (66%) had received testosterone replacement therapies prior to the review in clinics. Eleven patients (6.1%) had at least one venous thromboembolic event. The median age of the first venous thromboembolic event was 35 years (range: 19–73 y). The incidence of a venous thromboembolic event was 17.0 (95% confidence interval: 8.5–30.3) events per 10,000 person-years. Five of the 11 patients had received testosterone replacement therapies prior to venous thromboembolic events. There was no significant association between receiving testosterone replacement therapy and suffering a venous thromboembolic event (p=0.1). The incidence rate of the venous thromboembolic event in Klinefelter syndrome 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 the age. This study did not show a statistically significant difference in venous thromboembolic event incidence based on the use of testosterone replacement therapies.

Keywords

Klinefelter syndrome - venous thromboembolism - testosterone replacement therapy - incidence rate

Publication History

Received: 03 June 2025

Accepted after revision: 16 December 2025

Accepted Manuscript online:
18 December 2025

Article published online:
21 January 2026

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