Testosterone Replacement Therapy and Klinefelter Syndrome

Q: A 28-year-old male with known Klinefelter syndrome and previous Deep Venous Thromboses (DVTs) is admitted to ICU with pulmonary embolism (PE) after missing his anticoagulation tablets while on vacation. One of the permanent treatments besides anticoagulation in this clinical scenario is tеѕtοѕtеrone therapy.

A) True

B) False

Answer: A

Although tеѕtοѕtеrone therapy is conventionally associated with a higher risk of DVTs, in Klinefelter syndrome, it reduces the risk.

Overall, patients with Klinefelter syndrome are at higher risk of ischemic heart disease, mitral valve prolapse, lower extremity varicose veins, venous stasis ulcers, DVT, PE, increased body fat, hypertension, dyslipidemia, and abnormal glucose homeostasis.

The increased risk of DVT and PE is due to impaired fibrinolysis secondary to supernumerary X chromosome(s). Tеѕtοѕtеrone therapy reduces the thrombotic risk by decreasing serum fibrinogen and body fat in hypogonadal mаlеѕ.

#genetics

#cardiology

#hematology

#metabolism

References:

1. Gravholt CH, Chang S, Wallentin M, et al. Klinefelter Syndrome: Integrating Genetics, Neuropsychology, and Endocrinology. Endocr Rev 2018; 39:389.

2. Chang S, Christiansen CF, Bojesen A, et al. Klinefelter syndrome and testosterone treatment: a national cohort study on thrombosis risk. Endocr Connect 2020; 9:34.

3. Chang S, Biltoft D, Skakkebæk A, et al. Testosterone treatment and association with thrombin generation and coagulation inhibition in Klinefelter syndrome: A cross-sectional study. Thromb Res 2019; 182:175.

4. Chang S, Just J, Skakkebæk A, et al. Testosterone Replacement Therapy in Klinefelter Syndrome-Follow-up Study Associating Hemostasis and RNA Expression. J Clin Endocrinol Metab 2024; 109:978.