Cardiovascular Safety of Testosterone-Replacement Therapy
The cardiovascular safety of testosterone-replacement therapy in middle-aged and older men with hypogonadism has not been determined.
METHODS
In a multicenter, randomized, double-blind, placebo-controlled, noninferiority trial, we enrolled 5246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng per deciliter. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 350 and 750 ng per deciliter) or placebo gel. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-event analysis. A secondary cardiovascular end point was the first occurrence of any component of the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, assessed in a time-to-event analysis. Noninferiority required an upper limit of less than 1.5 for the 95% confidence interval of the hazard ratio among patients receiving at least one dose of testosterone or placebo.
RESULTS
The mean (±SD) duration of treatment was 21.7±14.1 months, and the mean follow-up was 33.0±12.1 months. A primary cardiovascular end-point event occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.78 to 1.17; P<0.001 for noninferiority). Similar findings were observed in sensitivity analyses in which data on events were censored at various times after discontinuation of testosterone or placebo. The incidence of secondary end-point events or of each of the events of the composite primary cardiovascular end point appeared to be similar in the two groups. A higher incidence of atrial fibrillation, of acute kidney injury, and of pulmonary embolism was observed in the testosterone group.
CONCLUSIONS
In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events.
A Michael Lincoff, Shalender Bhasin, Panagiotis Flevaris, Lisa M Mitchell, Shehzad Basaria, William E Boden, Glenn R Cunningham, Christopher B Granger, Mohit Khera, Ian M Thompson Jr, Qiuqing Wang, Kathy Wolski, Deborah Davey, Vidyasagar Kalahasti, Nader Khan, Michael G Miller, Michael C Snabes, Anna Chan, Elena Dubcenco, Xue Li, Tingting Yi, Bidan Huang, Karol M Pencina, Thomas G Travison, Steven E Nissen; TRAVERSE Study Investigators
Cleveland Clinic Coordinating Center for Clinical Research, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland (A.M.L., L.M.M., Q.W., K.W., D.D., V.K., S.E.N.); the Research Program in Men’s Health: Aging and Metabolism, Brigham and Women’s Hospital, Harvard Medical School (S. Bhasin, S. Basaria, K.M.P.), Veterans Affairs Boston Healthcare System and Massachusetts Veterans Epidemiology, Research, and Information Center, Boston University School of Medicine (W.E.B.), and Marcus Institute for Aging Research, Beth Israel Deaconess Medical Center, Harvard Medical School (T.G.T.) — all in Boston; AbbVie, North Chicago, IL (P.F., N.K., M.G.M., M.C.S., A.C., E.D., X.L., T.Y., B.H.); Baylor College of Medicine, Houston (G.R.C., M.K.), and CHRISTUS Santa Rosa Health System and the University of Texas Health Science Center, San Antonio (I.M.T.) — all in Texas; and Duke Clinical Research Institute, Durham, NC (C.B.G.).
Source: Lincoff et al. "Cardiovascular Safety of Testosterone-Replacement Therapy" New England Journal of Medicine | NEJM. (2023).