Testosterone, thrombophilia, thrombosis

We screened previously undiagnosed thrombophilia (V Leiden-prothrombin mutations, Factors VIII and XI, homocysteine, and antiphospholipid antibody (APL) syndrome) in 15 men and 2 women with venous thromboembolism (VIE) or osteonecrosis 7 months (median) after starting testosterone therapy (Pi), gel (30-50 mg/d), intramuscular (100-400 mg/wk), or human chorionic gonadotropin (HCG) (6000 IU/wk). Thrombophilia was studied in 2 healthy control groups without thrombosis (97 normal controls, 31 subjects on Pi) and in a third control group (n = 22) with VIE, not on Pi. Of the 17 cases, 76% had >= 1 thrombophilia vs 19% of 97 normal controls (P < 0.0001), vs 29% of 31 Pi controls (P = 0.002). Cases differed from normal controls by Factor V Leiden (12% vs 0%, P = 0.021), by high Factor VIII (>150%) (24% vs 7%, P = 0.058), by high homocysteine (29% vs 5%, P = 0.007), and from both normal and 7 controls for APL syndrome (18% vs 2%, P = 0.023, vs 0%, P = 0.04). Despite adequate anticoagulation with Pi continued after the first deep venous thrombosis-pulmonary embolus (DVT-PE), 1 man sustained 3 DVT-PEs 5, 8, and 11 months later and a second man had 2 DVT-PEs 1 and 2 months later. Of the 10 cases with serum T measured on 7, 6 (60%) had supranormal T (>800 ng/dl) and of 9 with estradiol measured on Pi, 7 (78%) had supranormal levels (>42.6 pg/mL). Pi interacts with thrombophilia leading to thrombosis. U continuation in thrombophilic men is contraindicated because of recurrent thrombi despite anticoagulation. Screening for thrombophilia before starting Pi should identify subjects at high risk for VIE with an adverse the risk to benefit ratio for Pi .