Abstract | 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 post-randomization 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 non-significant reduction in mean QTcF in the testosterone group compared to 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.

Affiliations
1Research Program in Men’s Health: Aging and Metabolism, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115;
2Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey;
3Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden;
4Program on Aging, Hebrew Senior Life, Roslindale, MA;
5DWR Department of Geriatric Medicine, University of Oklahoma, Oklahoma City, OK;
6Kronos Longevity Research Institute, Phoenix, AZ;
7Phoenix VA Health Care System, Phoenix, AZ.

Thiago Gagliano-Jucá1,*, Tevhide Betül İçli2,*, Karol M. Pencina1, Zhuoying Li1, John Tapper3, Grace Huang1, Thomas G. Travison4, Panayiotis Tsitouras5,6, S. Mitchell Harman6,7, Thomas W. Storer1, Shalender Bhasin1, Shehzad Basaria1

Corresponding Author: Thiago Gagliano-Jucá, MD, PhD, Research Program in Men’s Health: Aging and Metabolism, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Ave, Boston, MA 02115. Phone: +1 617-525-9150, Fax: +1 617-525-9148, Email: tgagliano@partners.org
*These authors contributed equally.
DOI: http://dx.doi.org/10.1210/jc.2016-3669
Received: November 09, 2016
Accepted: December 16, 2016
First Published Online: December 19, 2016

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