ArticleJournal of cardiovascular pharmacology2025
Dihydrotestosterone Pretreatment Diminishes the Severity of Drug-Induced Torsades de Pointes.
Article in Journal of cardiovascular pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
abstractTestosterone and dihydrotestosterone (DHT) attenuate drug-induced lengthening of ventricular repolarization, but it is unknown whether they influence drug-induced torsades de pointes (TdP). We tested the hypothesis that DHT reduces the incidence and severity of drug-induced TdP. Male New Zealand white rabbits underwent orchiectomy and were implanted with 2 subcutaneous sustained-release pellets containing DHT 50 mg (100 mg, n = 23) or placebo (n = 20). After 7 days, hearts were excised, mounted, and perfused with modified Krebs-Henseleit solution. The atrioventricular node was destroyed manually. Dofetilide 100 nM was perfused for 30 minutes. Median (Q 1 , Q 3 ) serum DHT concentrations were higher in DHT-treated rabbits [314.0 (232.5, 388.6) vs. 32.5 (28.5, 36.2) ng/dL, P < 0.0001]. The incidence of TdP in the DHT and placebo groups was 6/23 (26%) versus 8/20 (40%), respectively ( P = 0.33). In hearts that developed TdP, the median (Q 1 , Q3) number of episodes was lower in the DHT group [2 (2, 3.5) vs. 18.5 (12.5, 20.5), P = 0.01]. The median time to first TdP episode was longer [18.5 (17.3, 21.3) vs. 10.5 (12.5, 20.5) minutes, P = 0.01], and the TdP burden (median total number of TdP beats per heart) was lower in the DHT group [11.5 (9.5-46.5) vs. 271 (99.3-440.3) beats, P = 0.007]. Pre-dofetilide Fridericia-corrected QT intervals were shorter in the DHT group [377 (366, 390) vs. 385 (378, 401) ms, P = 0.02]. Maximum Fridericia-corrected QT interval during dofetilide perfusion was shorter in the DHT group [399 (390, 410) vs. 414 (399, 442) ms, P = 0.007]. In conclusion, DHT diminishes the severity of dofetilide-induced TdP.
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