Experts review evidence on testosterone and prostate cancer

In part 2 of this series on testosterone and prostate cancer, Abraham Morgentaler, MD, reviews evidence from randomized trials and biopsy studies examining the relationship between testosterone levels, testosterone therapy, and prostate cancer risk.

Morgentaler discusses findings from the TRAVERSE trial (NCT03518034), the largest randomized controlled trial of testosterone therapy to date. Among more than 5000 men, prostate cancer was diagnosed in 12 men receiving testosterone and 11 receiving placebo (P = .87).¹ He also highlights prostate biopsy data from the PCPT and REDUCE (NCT00056407) trials, which found no relationship between testosterone levels and prostate cancer risk among men in the control groups.^2,3 According to Morgentaler, these findings provide evidence against an association between higher testosterone levels or testosterone therapy and increased prostate cancer risk.

Morgentaler also describes population-level and randomized trial data showing similar prostate cancer rates among testosterone users and placebo recipients, and discusses why lowering testosterone with androgen deprivation therapy does not mean that raising testosterone necessarily increases cancer risk. He explains the saturation model, in which androgen receptors become saturated at relatively low testosterone concentrations, limiting the ability of additional testosterone to further stimulate prostate cell activity. According to this model, testosterone supplementation may increase prostate-specific antigen when levels are below the saturation point, but additional testosterone above that point would not be expected to further increase prostate cell proliferation. Morgentaler concludes by describing testosterone as unique among factors required for prostate cell function because it can be reduced to very low levels therapeutically without compromising survival.

REFERENCES
1. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;389(2):107-117.doi:10.1056/NEJMoa2215025

2. Thompson Jr IM, Goodman PJ, Tangen CM, et al. Long-term survival of participants in the prostate cancer prevention trial. N Engl J Med. 2013;369(7):603-10.doi: 10.1056/NEJMoa1215932

3. Muller RL, Gerber L, Moreira DM, et al. Serum testosterone and dihydrotestosterone and prostate cancer risk in the placebo arm of the Reduction by Dutasteride of Prostate Cancer Events trial. Eur Urol. 2012;62(5):757-64. doi:10.1016/j.eururo.2012.05.025.