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 ≥ 65 years of age (n = 14) were randomized to receive transdermal testosterone 100 mg, oral progesterone 400 mg, or matching transdermal/oral placebo daily for 7 days. On the morning following the seventh day, subjects received intravenous ibutilide 0.003 mg/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 ± 21 ms, P = 0.002). Maximum post-ibutilide J-Tpeak c was also lower during the testosterone phase (233 ± 22 vs. 246 ± 29 vs. 248 ± 23 ms, P < 0.0001). Pre-ibutilide Tpeak -Tend was not significantly different during the three phases, but maximum post-ibutilide Tpeak -Tend was lower…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 14 participants or records.
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