Thromboembolism Peaking 3 Months after Starting Testosterone Therapy: Testosterone–Thrombophilia Interactions

Abstract

We assessed time of thrombotic events (venous thromboembolism (VTE)) after starting testosterone therapy (TT) in 21 men who sustained 23 VTE. The density of thrombotic events was greatest at 3 months after starting TT, with a rapid decline in events by 10 months. The 21 cases with VTE on TT differed from 110 patient controls with unprovoked VTE, not taking TT (VTE-no TT) for Factor V Leiden heterozygosity (FVL) (33 per cent vs 13 per cent, P=0.037), for high lipoprotein (a) (Lp(a)) (55 per cent vs 17 per cent, P=0.012), and for the lupus anticoagulant (33 per cent vs 4 per cent, P=0.003). These differences between cases and VTE-no TT controls were independent of age and gender. TT can interact with underlying thrombophilia-hypofibrinolysis promoting VTE. We suggest that TT should not be started in subjects with known thrombophilia. Coagulation screening, particularly for the FVL , Lp(a), and the lupus anticoagulant should be considered before starting TT, to identify men at high VTE risk who have an adverse risk/benefit ratio for TT.

Testosterone Therapy, Thrombophilia, Venous Thromboembolism, and Thrombotic Events

“…In 2018 [16], we reported thrombotic events after starting TT in 21 men who sustained 23 VTEs. These 21 patients were referred to us and were studied sequentially after our first 67 patients [15].…”

“…The 21 cases with VTE on TT [16] differed from 110 patient controls with unprovoked VTE, not taking TT (VTE-no TT controls) for FVL heterozygosity (33% vs. 13%, p = 0.037), for high lipoprotein(a) (Lp(a)) (55% vs. 17%, p = 0.012), and for the lupus anticoagulant (33% vs. 4%, p = 0.003). These differences between cases and VTE-no TT controls were independent of age and gender.…”

“…The results from our studies of 21 [16] and 67 cases [15] with VTEs on TT were pooled ( n = 88), since they were sequential but separate sets of patients without overlap. These two studies had the same inclusion and exclusion criteria, did not differ by age or gender ( p > 0.05), did not differ by familial or acquired thrombophilia characteristics ( p > 0.05), followed the same protocol in in the same thrombosis research center, and used the same coagulation laboratory, the same control group, and the same investigator group.…”

“…In 29 of the 79 men in our two studies [15,16], we were able to recover measures of serum total and free testosterone and estradiol (E2), which had been obtained before TT and subsequently after a median of 6 months on TT (Table 1). Two-thirds of the men had low T and free T before TT and one-third had normal levels (Table 1).…”

“…Our studies of 67 and 21 patients with VTE after starting TT, and in 111 controls with VTE not taking TT (VTE-no TT), were carried out with signed informed consent, following protocols approved by our institutional Institutional Review Board IRB [15,16], as were our other studies of TT, thrombophilia, and thrombosis [17,18].…”