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Testosterone Supplementation and the Risk of Venous Thrombosis and Osteonecrosis

Charles J. Glueck, MD
March, 2014

Editor's Note from Henry I. Bussey, Pharm.D.: Dr. Charles J. Glueck of the Jewish Hospital of Cincinnati (cjglueck@health-partners.org) who has previously shared his work on the relationship of testosterone supplementation and venous thrombosis and osteonecrosis (see clotcare.org/testosterone_factor_v_clot_risk.aspx and clotcare.org/dvt_pe_testosterone_women.aspx) has provided ClotCare with the following summary of updated information.


We have recently published three studies documenting the relationship between exogenous testosterone therapy (TT) and thrombotic events (1-3). We evaluated thrombophilia-hypofibrinolysis in 14 men and 1 woman referred to us after developing deep venous thrombosis (DVT)-pulmonary emboli (PE) and hip-knee osteonecrosis (n=5) that developed after testosterone therapy (median 11 months) (1). The subjects had been previously healthy with no antecedent thrombosis. Of the 14 patients, 3 had factor V Leiden heterozygosity, 3 had high factor VIII, 3 and PAI-4G4G homozygosity, 2 had high factor XI, 2 had high homocysteine, 1 had low antithrombin III, 1 had the lupus anticoagulant, 1 had high ACLA. In 4 men with thrombophilia, DVT-PE recurred despite therapeutic INR on warfarin.

In a study of 3 postmenopausal women receiving TT for low libido, central retinal vein thrombosis (n=1), and osteonecrosis (n=2) developed at 16 days, 2 months, and 11 months after starting TT. The women were found to have G20210A Prothrombin gene heterozygosity, high homocysteine, and 4G4G PAI-1 homozygosity respectively (2)

In an assessment of 596 men hospitalized for DVT-PE, we found that 1.2% of the cohort had taken TT before and at the time of their admission, with DVT-PE occurring within 2 months (median) after starting TT. All 5 men who had evaluation of coagulation were found to have previously undiagnosed familial or acquired thrombophilia-hypofibrinolysis (3).

References

  1. Glueck CJ, Richardson-Royer C, Schultz R, et al. Testosterone, thrombophilia, and thrombosis. Clin Appl Thromb Haemost 2014;20:22-30.

  2. Glueck CJ, Bowe D, Valdez A et al. Thrombosis in three postmenopausal women receiving testosterone therapy for low libido. Women’s Health 2013;9:405-410.

  3. Glueck CJ, Richardson-Royer C, Schultz R, et al. Testosterone therapy, thrombophilia-hypofibrinolysis, and hospitalization for deep venous thrombosis-pulmonary embolus: an exploratory, hypothesis-generating study. Clin Appl Thromb Hemost 2014;20;244-249.
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