madman
Super Moderator
Abstract: In our sequential studies of 67 and 21 patients, testosterone therapy (TT) interacted with thrombophilia–hypofibrinolysis, leading to venous thromboembolism (VTE). Compared to 111 VTE controls not taking TT (VTE-no TT), the 67 and 21 cases were more likely (p < 0.05 for all) to have Factor V Leiden (FVL) heterogeneity (24% and 33% vs. 12%), the lupus anticoagulant (14% and 33% vs. 4%), and high lipoprotein(a) (33% vs. 13%, n = 21). After a first VTE and continuing TT, 11 thrombophilic cases had a second VTE despite adequate anticoagulation, 6 of whom, still anticoagulated, had a third VTE. The greatest density of thrombotic events was at three months after starting TT, with a rapid decline by 10 months. From <1 to 8 months after starting TT, 65% of VTE occurred, which may reflect TT-induced depletion of susceptible thrombophilic patients, leaving a winnowed residual group with fewer VTE events despite the continuation of TT. Before starting TT, we suggest screening for FVL, lipoprotein(a), and the lupus anticoagulant to identify patients at increased VTE risk, with an adverse risk-to-benefit ratio for TT. We suggest that TT should not be started in patients with known thrombophilia–hypofibrinolysis, and should not be continued after a first VTE. When TT is given to patients with thrombophilia–hypofibrinolysis, VTE may occur and then recur despite adequate anticoagulation
5. Conclusions
Our two recent studies of 88 patients (67 [15] and 21 [16] altogether) revealed VTE associated with FVL heterozygosity, the lupus anticoagulant, and lipoprotein(a), peaking three months after starting TT. These studies provide further evidence altogether congruent with the 2014 FDA warning on the TT-associated risks of VTE[2]. We suggest that TT should not be started in patients with known familia lor acquired thrombophilia, and recommend screening for familial and acquired thrombophilia, particularly FVL and the lupus anticoagulant, before starting TT, to identify men and women at high risk for VTE with an adverse risk-to-benefit ratio for TT. When TT is given to patients with familial and acquired thrombophilia, thrombosis may occur and recur despite adequate anticoagulation if TT is continued. In patients who have sustained VTE while taking TT, a laboratory evaluation for thrombophilia–hypofibrinolysis should be done. In patients with thrombophilia and a VTE event on TT, the TT should be stopped and not resumed, since recurrent VTE may occur despite adequate concurrent anticoagulation.
5. Conclusions
Our two recent studies of 88 patients (67 [15] and 21 [16] altogether) revealed VTE associated with FVL heterozygosity, the lupus anticoagulant, and lipoprotein(a), peaking three months after starting TT. These studies provide further evidence altogether congruent with the 2014 FDA warning on the TT-associated risks of VTE[2]. We suggest that TT should not be started in patients with known familia lor acquired thrombophilia, and recommend screening for familial and acquired thrombophilia, particularly FVL and the lupus anticoagulant, before starting TT, to identify men and women at high risk for VTE with an adverse risk-to-benefit ratio for TT. When TT is given to patients with familial and acquired thrombophilia, thrombosis may occur and recur despite adequate anticoagulation if TT is continued. In patients who have sustained VTE while taking TT, a laboratory evaluation for thrombophilia–hypofibrinolysis should be done. In patients with thrombophilia and a VTE event on TT, the TT should be stopped and not resumed, since recurrent VTE may occur despite adequate concurrent anticoagulation.
