The prostate has been the oldest objection to testosterone therapy. The TRAVERSE prostate sub-study tested it in 5,204 men over 14,304 person-years and found high-grade prostate cancer in 5 men (0.19%) on testosterone versus 3 (0.12%) on placebo — hazard ratio 1.62, 95% CI 0.39 to 6.77, P = .51.[1] Incidences of any prostate cancer, acute urinary retention, invasive prostate procedures, prostate biopsy and new drug treatment for lower urinary tract symptoms also did not differ significantly.
The result is reassuring. The conditions attached to it are what turn it into clinical guidance rather than a slogan.
Where the objection came from
The concern traces to the 1940s observation that androgen deprivation causes prostate cancers to regress. The inference — if removing testosterone shrinks the tumour, adding it must grow one — held for decades on the strength of the logic rather than trial evidence.
TRAVERSE is the first randomized trial large enough, long enough, and with adjudicated prostate endpoints to test it properly.
What the sub-study did
- Population: 5,246 men enrolled, 5,204 analyzed, mean age 63.3, across 316 US sites.
- Eligibility: two testosterone concentrations below 300 ng/dL, hypogonadal symptoms, and cardiovascular disease or increased cardiovascular risk.
- Excluded: men with PSA above 3.0 ng/mL and men with an International Prostate Symptom Score above 19.
- Baseline: mean PSA 0.92 ng/mL; mean IPSS 7.1.
- Intervention: topical 1.62% testosterone gel or placebo, randomized with stratification for prior cardiovascular disease.
- Mean treatment duration: 21.8 months on testosterone, 21.6 on placebo. Follow-up: 14,304 person-years.
- Primary endpoint: adjudicated high-grade prostate cancer (Gleason ≥ 4+3).
What it found
High-grade prostate cancer: 5 of 2,596 (0.19%) on testosterone versus 3 of 2,602 (0.12%) on placebo. Hazard ratio 1.62 (95% CI, 0.39–6.77), P = .51.[1]
No significant difference in any prostate cancer, acute urinary retention, invasive surgical procedure, prostate biopsy, or new pharmacologic treatment for urinary symptoms. Change in IPSS did not differ between groups — testosterone did not worsen urinary symptoms.
One difference was real: PSA rose more in testosterone-treated men than in placebo-treated men, concentrated in the first year of treatment.
Read the confidence interval honestly. It runs from 0.39 to 6.77 — consistent with a substantial reduction and with a nearly seven-fold increase. With eight events in total across both arms, this trial demonstrates that high-grade prostate cancer was rare in a screened population. It is not precise enough to rule out a modest effect.
The screening is the finding
The authors qualify their own conclusion carefully: in men "carefully evaluated to exclude those at high risk of prostate cancer," prostate event rates were low and did not differ.[1]
That qualifier is doing real work. Men with PSA above 3.0 and men with severe urinary symptoms were never enrolled. The trial therefore says something specific and useful — testosterone did not appear to raise prostate risk in men who were screened before starting — and says nothing at all about men who would have failed that screen.
Which makes the practical translation straightforward: the baseline prostate assessment is not paperwork. It is the condition under which this reassurance applies.
What it means for monitoring
- Baseline PSA before starting, with the trial's own thresholds as a reference point for who was studied.
- Expect some PSA rise in year one. It happened in the trial and is not by itself evidence of cancer — but it does mean a rising PSA needs interpreting against that expectation rather than read cold.
- Urinary symptoms are worth scoring at baseline, since men with severe symptoms were excluded from the evidence base.
- A history of prostate cancer is a different conversation entirely and is outside what this trial addresses.
This connects to the broader monitoring picture in what your clinician is looking for at three months and the short list of what belongs on a testosterone panel.
Bottom line
TRAVERSE found no significant difference in high-grade prostate cancer, any prostate cancer, or adverse urinary events between testosterone and placebo, over roughly two years of treatment in men screened to exclude high prostate risk. The event numbers are small and the confidence interval is wide, so this is evidence of low absolute risk in a screened population rather than proof of no effect. The screening that produced it is the part to carry into practice.
References
1 source
- Bhasin S, Travison TG, Pencina KM, et al. Prostate Safety Events During Testosterone Replacement Therapy in Men With Hypogonadism: A Randomized Clinical Trial. JAMA Netw Open. 2023;6(12):e2348692. doi:10.1001/jamanetworkopen.2023.48692 · PMID 38150256
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