Prostate Risk and Monitoring During Testosterone Replacement Therapy.

Men with hypogonadism have a reduced risk of prostate cancer mortality compared to eugonadal men.

• This reduced risk is noted as background context for evaluating testosterone replacement therapy safety.
• Whether testosterone treatment increases the risk of prostate safety events in men with hypogonadism remains controversial.
• This finding motivates the need for prospective randomized trials to assess prostate safety during TRT.

Four larger randomized trials treated men with testosterone or placebo for 1 year or longer and reported prospectively ascertained prostate safety data.

• The four trials identified were: the Testosterone Trials, TEstosterone and Atherosclerosis Progression in Aging Men (TEAAM) trial, Testosterone for Diabetes Mellitus trial, and the TRAVERSE trial.
• The TRAVERSE trial was noted as providing the most comprehensive data due to its large size, longer duration, and adjudication of prostate events.
• All four trials prospectively ascertained prostate safety outcomes.

In the TRAVERSE trial, incidences of high-grade or any prostate cancer, acute urinary retention, surgical procedures for BPH, prostate biopsy, or new pharmacologic therapy for lower urinary tract symptoms were low and did not differ between testosterone and placebo groups.

• Men were carefully screened to exclude those at high risk of prostate cancer prior to enrollment.
• Prostate events were adjudicated in the TRAVERSE trial, providing rigorous outcome ascertainment.
• No statistically significant differences were observed between testosterone and placebo groups for any of these prostate safety endpoints.

Testosterone did not worsen lower urinary tract symptoms (LUTS) in men with hypogonadism.

• This finding was reported across the reviewed randomized trials including the TRAVERSE trial.
• LUTS outcomes were prospectively monitored as part of prostate safety assessments.
• New pharmacologic therapy for LUTS did not differ between testosterone and placebo groups.

Testosterone replacement therapy was associated with a greater increase in prostate-specific antigen (PSA) than placebo in the first year of treatment.

• The PSA increase was observed in the first year of TRT.
• Despite the PSA increase, rates of prostate biopsy and prostate cancer detection did not significantly differ between treatment groups.
• This PSA elevation during TRT requires monitoring to distinguish benign androgen-mediated PSA changes from clinically significant prostate cancer signals.

Baseline evaluation of prostate cancer risk and a standardized monitoring plan can minimize unnecessary prostate biopsy while enabling detection of high-grade prostate cancers during TRT.

• A structured approach to prostate cancer risk assessment before initiating TRT is recommended.
• Standardized monitoring during TRT is proposed to balance detection of clinically significant cancers against overdiagnosis and unnecessary procedures.
• Men at high risk of prostate cancer were excluded from trials, forming the basis of this screening recommendation.