Effects of Testosterone Replacement on Electrocardiographic Parameters in Men: Findings From Two Randomized Trials.

Context: Endogenous testosterone levels have been negatively associated with QTc interval in small case series; the effects of testosterone therapy on electrocardiographic parameters have not been evaluated in randomized trials. Objective: To evaluate the effects of testosterone replacement on corrected QT interval (QTcF) in two randomized controlled trials. Participants: Men with pre- and postrandomization electrocardiograms (ECGs) from the Testosterone and Pain (TAP) and the Testosterone Effects on Atherosclerosis in Aging Men (TEAAM) Trials. Interventions: Participants were randomized to either placebo or testosterone gel for 14 weeks (TAP) or 36 months (TEAAM). ECGs were performed at baseline and at the end of interventions in both trials; in the TEAAM trial ECGs were also obtained at 12 and 24 months. Outcomes: Difference in change in the QTcF between testosterone and placebo groups was assessed in each trial. Association of changes in testosterone levels with changes in QTcF was analyzed in men assigned to the testosterone group of each trial.
Results: Mean total testosterone levels increased in the testosterone group of both trials. In the TAP trial, there was a nonsignificant reduction in mean QTcF in the testosterone group compared with placebo (effect size = -4.72 ms; P = 0.228) and the changes in QTcF were negatively associated to changes in circulating testosterone (P = 0.036). In the TEAAM trial, testosterone attenuated the age-related increase in QTcF seen in the placebo group (effect size= -6.30 ms; P < 0.001).
Conclusion: Testosterone replacement attenuated the age-related increase in QTcF duration in men. The clinical implications of these findings require further investigation.

RCT Entities:   Population Interventions Outcomes