Transdermal Testosterone Attenuates Drug-Induced Lengthening of Both Early and Late Ventricular Repolarization in Older Men.

Abstract

We have previously reported that transdermal testosterone attenuates drug-induced QT interval lengthening in older men. However, it is unknown whether this is due to modulation of early ventricular repolarization, late repolarization, or both. In a secondary analysis of a prospective, randomized, double-blind, placebo-controlled three-way crossover study, we determined if transdermal testosterone and oral progesterone attenuate drug-induced lengthening of early and late ventricular repolarization, represented by the electrocardiographic measurements J-Tpeak c and Tpeak -Tend , respectively, as well as Tpeak -Tend /QT, a measure of transmural dispersion of repolarization. Male volunteers ≥65years of age (n=14) were randomized to receive transdermal testosterone 100mg, oral progesterone 400mg, or matching transdermal/oral placebo daily for 7days. On the morning following the seventh day, subjects received intravenous ibutilide 0.003mg/kg, after which electrocardiograms were performed serially. One subject was excluded due to difficulty in T-wave interpretation. Pre-ibutilide J-Tpeak c was lower during the testosterone phase than during progesterone and placebo (216±23 vs. 227±28 vs. 227±21ms, P=0.002). Maximum post-ibutilide J-Tpeak c was also lower during the testosterone phase (233±22 vs. 246±29 vs. 248±23ms, P<0.0001). Pre-ibutilide Tpeak -Tend was not significantly different during the three phases, but maximum post-ibutilide Tpeak -Tend was lower during the testosterone phase (80±12 vs. 89±18 vs. 86±15ms, P=0.002). Maximum Tpeak -Tend /QT was also lower during the testosterone phase (0.199±0.023 vs. 0.216±0.035 vs. 0.209±0.031, P=0.005). Progesterone exerted minimal effect on drug-induced lengthening of J-Tpeak c, and no effect on Tpeak -Tend or Tpeak -Tend /QT. Transdermal testosterone attenuates drug-induced lengthening of both early and late ventricular repolarization in older men.