Testosterone therapy, thrombophilia, and hospitalization for deep venous thrombosis-pulmonary embolus, an exploratory, hypothesis-generating study.

Our hypothesis was that testosterone therapy (TT) interacts with previously undiagnosed thrombophilia-hypofibrinolysis, leading to hospitalization for deep venous thrombosis (DVT)-pulmonary emboli (PE). We determined the prevalence of DVT-PE associated with TT 147 men hospitalized in the last 12 months for DVT-PE. Of the 147 men, 2 (1.4%) had TT before and at the time of their DVT-PE. Neither had risk factors for thrombosis. Neither smoked. Case #1 (intramuscular T 50mg/week) had 2 PE, 6 and 24 months after starting TT. DVT-PE in case #2 (T gel 100mg/day) occurred 24 months after starting T. Both men were found to have previously undiagnosed familial thrombophilia (protein S deficiency, homocysteinemia, high Factor VIII). In case #2, on 100mg T gel/day, serum estradiol was high, 51 pg/ml (upper normal limit 42.6 pg/ml). At least 1.4% of men hospitalized for DVT-PE were on TT and had previously undiagnosed thrombophilia, suggesting a thrombotic interaction between exogenous T and thrombophilia-hypofibrinolysis. Given the increasing use of TT, our preliminary findings should facilitate design of a much-needed, multi-center, prospective study of pro-thrombotic interactions between T therapy and thrombophilia for subsequent thrombotic events including DVT-PE.