In a randomised trial, testosterone therapy did not increase risk for prostate cancer or progressive lower urinary tract symptoms.

Because of longstanding concern that testosterone therapy might cause prostate cancer or worsen symptoms of benign prostatic hyperplasia (BPH), researchers tracked prostate outcomes in the TRAVERSE study, a randomized trial designed mainly to examine the cardiovascular safety of testosterone therapy (NEJM JW Gen Med Jul 15 2023 and N Engl J Med 2023; 389: 107-117). About 5200 men (mean age, 63 years) with testosterone levels between 100 and 300 mcg/L received either transdermal testosterone or placebo; men with prostate-specific antigen (PSA) levels above 3.0 mcg/L or severe BPH symptoms were excluded. PSA levels and urinary symptoms were monitored regularly during the trial, and indications for urology referral were prespecified.

During average follow up of 33 months, the incidence of prostate cancer was less than 1% – and not significantly different – in the testosterone and placebo groups. Only a few cases of high-grade cancer were diagnosed in each group. Changes in urinary symptom scores were similar in the two groups throughout follow up. PSA levels rose slightly more with testosterone than with placebo, but mean differences were small (about 0.1 mcg/L) at most time points.

Comment: Two or three years of testosterone therapy does not appear to cause clinically important prostate cancer or obstructive urinary symptoms in men with low serum testosterone levels. Note, however, that on-treatment testosterone levels averaged only about 400 mcg/L in this study; the safety of longer-duration treatment – or treatment resulting in higher blood levels of testosterone – remains unclear. We recently summarised another substudy from TRAVERSE on whether testosterone therapy prevents fractures (NEJM JW Gen Med Feb 1 2024 and N Engl J Med 2024; 390: 203-211).

Allan S. Brett, MD, Clinical Professor of Medicine, University of Colorado School of Medicine, Aurora, USA.

Bhasin S, et al. Prostate safety events during testosterone replacement therapy in men with hypogonadism: a randomized clinical trial. JAMA Netw Open 2023 Dec; 6: e2348692.