The link between testosterone replacement therapy (TRT) and prostate cancer has been a topic of debate for years, but the full impact still isn’t fully understood. While previous studies haven’t found a clear connection between testosterone levels and prostate cancer risk, experts are still cautious. One thing is clear: many professional guidelines suggest that men with a history or higher risk of prostate cancer should avoid TRT.

In 2015, the U.S. Food and Drug Administration (FDA) pushed for more research to determine if TRT affects cardiovascular events. This led to the TRAVERSE study, a large trial aimed at examining the long-term safety of TRT, including its potential impact on prostate health. The study was particularly useful because it was designed to investigate the risks of prostate cancer and other prostate-related issues, such as acute urinary retention, prostate surgery, and the use of new medications for benign prostatic hyperplasia (BPH).

The study, conducted at 316 sites across the U.S., included men aged 45 to 80 who had low testosterone levels and a history or increased risk of cardiovascular disease (CVD). The research focused on men who didn’t have a history of prostate cancer and excluded those with high PSA levels (a marker used to screen for prostate cancer), severe urinary symptoms, or other prostate issues. Participants were randomly assigned to receive either TRT or a placebo for the duration of the study.

The main goal was to assess whether TRT increased the risk of high-grade prostate cancer, any prostate cancer, or other prostate events like urinary retention or the need for surgery. A structured monitoring plan was put in place to track these outcomes, with careful attention given to avoid bias that could arise from TRT-induced PSA increases, which might prompt unnecessary biopsies.

After tracking the participants for an average of about three years, the results were promising. The rate of high-grade prostate cancer was low in both the TRT and placebo groups. There were only a handful of cases in each group, and the difference between the groups was not statistically significant. The same was true for overall prostate cancer cases, with very few diagnoses in either group.

There were also no major differences between the TRT and placebo groups when it came to other prostate issues like urinary retention, the need for invasive surgery, or starting new medications for prostate problems. However, more men in the TRT group did undergo prostate procedures, though this result wasn’t statistically significant.

While TRT was associated with a small increase in PSA levels, this was expected, as testosterone naturally stimulates PSA production. Interestingly, the increase in PSA levels plateaued after the first 12 months, and the difference between the TRT and placebo groups became much smaller over time.

Another key finding was that TRT didn’t worsen lower urinary tract symptoms, such as those associated with BPH. Both groups showed a similar increase in symptoms, with no significant differences between them.

In terms of safety, the study’s approach to managing PSA increases was effective. When PSA levels exceeded certain thresholds, participants were referred for further evaluation, including prostate biopsies if necessary. This careful monitoring ensured that biopsies were only done when truly needed, reducing the likelihood of unnecessary procedures.

The TRAVERSE study is one of the largest and most comprehensive trials of TRT to date. It offers reassuring data for men with low testosterone who are concerned about the risks of prostate cancer. For most men with low testosterone and a PSA level under 3.0 ng/mL, TRT appears to carry a low risk of prostate cancer and other prostate issues. However, the study has limitations, particularly because it didn’t include men with a history of prostate cancer or higher PSA levels. It also didn’t account for prostate imaging or other biomarkers that could help in decision-making.

Overall, the findings suggest that for men with low testosterone and no history of prostate issues, TRT seems to be a relatively safe option when carefully monitored. This could provide relief for many men experiencing symptoms of testosterone deficiency, without significantly increasing the risk of serious prostate problems.