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Men treated with testosterone replacement therapy (TRT) for hypogonadism didn't have an increase in adverse prostate events, the TRAVERSE trial found.

Over a mean follow-up of 33 months, those who used topical 1.62% testosterone gel had a 0.19% incidence of high-grade prostate cancer (Gleason score ≥4 + 3), similar to the 0.12% among placebo-treated men (HR 1.62, 95% CI 0.39-6.77, P=0.51), Shalender Bhasin, MBBS, of Brigham and Women's Hospital in Boston, and colleagues reported in .

The randomized trial included 5,246 men, and showed no between-group differences for the incidence of any prostate cancer (0.46% vs 0.42% for placebo), acute urinary retention (0.77% vs 0.61%), invasive surgical procedures (0.89% vs 0.46%), prostate biopsy (0.62% vs 0.54%), or new pharmacologic treatment (3.89% vs 3.34%) during 14,304 person-years of follow-up.

"The trial's findings indicate that in men with hypogonadism who were screened and monitored carefully using a structured protocol, the risk of high-grade or any prostate cancer and other prostate events is low," Bhasin's group wrote.

That being said, these findings don't apply to patients with known prostate cancer, those with higher prostate-specific antigen (PSA) values, or men who do not have confirmed hypogonadism.

Of note, this study only included men with hypogonadism without a history of prostate cancer and with PSA concentrations under 3.0 ng/mL, which applies to most of the aging U.S. population, said Bhasin's group.

The investigators reported that over more than 2 years of follow-up, International Prostate Symptom Score (IPSS) increased similarly for both study arms. A total of 7.9% reached a score greater than 19, including 7.5% of the testosterone group and 8.2% of the placebo group.

However, TRT was linked with a significant increase in PSA levels compared with placebo as early as 3 months (estimated between-group difference 0.11 ng/mL, 95% CI 0.07-0.15) and persisting to 12 months (0.15 ng/mL, 95% CI 0.08-0.21).

"Although PSA concentrations increased more among the TRT group than the placebo group, the mean increase was small and between-group difference did not widen after 12 months. Thus, in a population [of] men with hypogonadism and PSA concentrations less than 3 ng/mL who were evaluated carefully to exclude those at increased prostate cancer risk, TRT was associated with low risk of adverse prostate events, including cancer," the researchers wrote.

TRAVERSE had been conducted after the FDA required testosterone manufacturers to conduct a randomized clinical trial to assess the effect of TRT on major adverse cardiovascular events back in 2015.

Topline findings from the trial were first reported at ENDO 2023, the annual meeting of the Endocrine Society. In that report, TRT was cleared of major adverse cardiac event risk in men with hypogonadism and established or at high risk for cardiovascular disease.

Across 316 participating U.S. sites, TRAVERSE participants were randomly assigned to receive daily transdermal 1.62% testosterone gel -- a dose that was adjusted to maintain testosterone levels from 350 through 750 ng/dL -- or placebo gel.

For inclusion, the 5,204 study participants (all men ages 45-80) had to have two testosterone concentrations under 300 ng/dL, hypogonadal symptoms, and cardiovascular disease or increased risk of cardiovascular disease. Men with PSA concentrations over 3.0 ng/mL and IPSS greater than 19 were excluded.

The cohort averaged age 63 years at baseline. Mean PSA concentration was 0.92 ng/mL and IPSS was 7.1.

Men were treated for an average of 21.8 months in the testosterone group and 21.6 months in the placebo group. Nearly all of the participants (92%) had at least a year of follow-up, while 74% had 2 years, 57% had 3 years, and 2% had 4 years of follow-up.

Looking at the few participants who developed high-grade cancer or any prostate cancer, baseline PSA did not appear to be a factor.

"Although the TRAVERSE study was longer than most other randomized clinical trials of TRT, carcinogens may require many years to induce malignant neoplasms," the researchers cautioned.

"The concern about prostate risk heavily influences decision-making by clinicians and patients who are considering TRT for hypogonadism," they noted. "The study's findings will facilitate a more informed appraisal of the potential risks of TRT."

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