title: Effects of Testosterone Replacement on Electrocardiographic Parameters in Men: Findings From Two Randomized Trials.
abstract: 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.
  
  
  
  To evaluate the effects of testosterone replacement on corrected QT interval (QTcF) in two randomized controlled trials.
  
  
  
  Men with pre- and postrandomization electrocardiograms (ECGs) from the Testosterone and Pain (TAP) and the Testosterone Effects on Atherosclerosis in Aging Men (TEAAM) Trials.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  Testosterone replacement attenuated the age-related increase in QTcF duration in men. The clinical implications of these findings require further investigation.
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Thiago
authors.initials: T
authors.lastname: Gagliano-Jucá
authors.affiliation: Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Tevhide Betül
authors.initials: TB
authors.lastname: Içli
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Karol M
authors.initials: KM
authors.lastname: Pencina
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Zhuoying
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden.
authors.forename: John
authors.initials: J
authors.lastname: Tapper
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Grace
authors.initials: G
authors.lastname: Huang
authors.affiliation: Program on Aging, Hebrew Senior Life, Roslindale, Massachusetts 02131.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Travison
authors.affiliation: Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma, Oklahoma City, Oklahoma 73117.|Kronos Longevity Research Institute, Phoenix, Arizona 85016.
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Tsitouras
authors.affiliation: Kronos Longevity Research Institute, Phoenix, Arizona 85016.|Phoenix VA Health Care System, Phoenix, Arizona 85012.
authors.forename: S Mitchell
authors.initials: SM
authors.lastname: Harman
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Storer
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Shehzad
authors.initials: S
authors.lastname: Basaria
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000375:Aging; D000701:Analgesics, Opioid / Q000009:adverse effects; D000728:Androgens / Q000627:therapeutic use*; D004311:Double-Blind Method; D004562:Electrocardiography; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013739:Testosterone / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D000728:Androgens; D013739:Testosterone