The following is a summary of “Testosterone Replacement Therapy in Klinefelter Syndrome—Follow-up Study Associating Hemostasis and RNA Expression,” published in the April 2024 issue of Endocrinology by Chang, et al.

Men diagnosed with Klinefelter syndrome (KS) commonly experience hypergonadotropic hypogonadism, necessitating testosterone replacement therapy (TRT), and face a significantly elevated risk of thrombosis. While TRT in KS may influence thrombotic risk, data on this topic were limited. For a study, researchers sought to evaluate the effects of 18 months of TRT on hemostasis in KS and to identify genes associated with the prothrombotic phenotype.

Untreated and TRT-treated men with KS were enrolled at baseline and matched with healthy controls. TRT initiation occurred in untreated KS individuals, and all groups were reassessed after an 18-month follow-up period. Thrombin generation was assessed with and without thrombomodulin, and fibrin clot lysis was evaluated through turbidity measurements. RNA expression was analyzed in blood, fat, and muscle tissue from TRT-treated patients with KS and controls.

While thrombin generation with thrombomodulin was slightly elevated in untreated KS, overall, KS was not linked with a hypercoagulable state. However, patients with KS exhibited fibrinolytic impairment associated with higher body fat levels and fibrinogen. After 18 months of TRT, patients with KS experienced reductions in body fat and fibrinogen levels, thereby mitigating the prothrombotic profile. Additionally, elevated expression of ENPP4 was observed in patients with KS, suggesting its involvement in impaired fibrinolysis.

KS is characterized by a distinct expression profile contributing to fibrinolytic impairment and heightened thrombotic risk. TRT in patients with KS can potentially ameliorate the prothrombotic phenotype by reducing body fat and fibrinogen levels.

Reference: academic.oup.com/jcem/article-abstract/109/4/978/7420187