Luteinizing Hormone-Releasing Hormone Agonists are Superior to Subcapsular Orchiectomy in Lowering Testosterone Levels of Men with Prostate Cancer: Results from a Randomized Clinical Trial

PURPOSE: Recent evidence suggests that reaching the lowest achievable levels of testosterone with androgen deprivation therapy delays disease progression and increases overall survival in men with advanced prostate cancer. The aim of this analysis is to compare the post-treatment serum testosterone levels between patients undergoing subcapsular orchiectomy and patients treated with the luteinizing hormone-releasing hormone agonist triptorelin.

MATERIAL AND METHODS: In this randomized clinical trial, we included 58 consecutive hormone-naive men diagnosed with advanced prostate cancer at Herlev and Gentofte University Hospital, Denmark, from September 2013 to March 2015. Follow-up was 48 weeks. Participants were randomly assigned (1:1) to either subcapsular orchiectomy or triptorelin 22.5 mg given as 24 week depot injections. Androgen status was measured by liquid chromatography tandem mass spectrometry prior to treatment and after 12, 24 and 48 weeks. Between-group differences in achieved hormone levels were analyzed using longitudinal Tobit regressions.

RESULTS: Triptorelin injections resulted in 29% (95% CI 17.2, 41.7) lower testosterone levels compared to subcapsular orchiectomy (p<.001). A significantly higher proportion of men receiving triptorelin had testosterone levels <20 ng/dL at 12 and 48 weeks compared to men undergoing orchiectomy (97% versus 79% and 100% versus 87%, p<.05). There was no detectable difference in adrenal androgen reductions between treatment groups.

CONCLUSIONS: The use of 24-week depot triptorelin injections results in significantly lower testosterone levels compared to subcapsular orchiectomy. This is the first randomized study to demonstrate a difference in treatment effect between surgical and medical castration on testosterone levels.