Testosterone replacement therapy (TRT) application in patients with prostate cancer (PC) remains highly controversial, despite a growing body of evidence showing it may be safely applied and beneficial for sexual function recovery post radical prostatectomy (RP).^1,2 PC’s complex relationship with androgens was first established by Huggins and Hodges in 1941, noting castration reduced tumor burden while testosterone had the opposite effect.³ Gann et al⁴ furthered this concept in the Physician Health Study, demonstrating that higher levels of testosterone were associated with an increased risk of PC. However, recent analyses have countered these findings and identified an increased prevalence of PC in men with low testosterone levels.^5-8 Moreover, recent evidence suggests that TRT is safe after initial PC treatment and may delay biochemical recurrence (BCR).^9,10 Within this context, the present study aims to retrospectively assess the efficacy of TRT on potency recovery in hypogonadal men aged 60 or older over a 2-year period following robot-assisted RP (RARP).

Conducted at the Department of Urology, University of California, Irvine Health, this retrospective, case-control study analyzed data from 70 hypogonadal men aged 60 or older who underwent RP between October 2016 and October 2020. Patients were stratified based on whether they received TRT postoperatively. Baseline demographics, including total testosterone, calculated free testosterone, and comorbidities prior to RP, were recorded. Sexual function was assessed using the International Index of Erectile Function (IIEF-5) before and after surgery. Potency outcomes were evaluated at 3, 9, 15, and 24 months post RP, defined as achieving erections sufficient for penetration and are satisfying (orgasm), “erection fullness” > 75%, or a score of 5 on Q1 of the IIEF-5 questionnaire. Statistical analyses included t tests, X² tests for primary potency outcomes, and regression analyses to adjust for age and Gleason Grade Group. Time to BCR was assessed using Kaplan-Meier analysis and plotted as a percentage survival curve, stratified by TRT. A P value of < .05 was considered to be statistically significant.

Demographic characteristics of the TRT-receiving vs no-TRT group are displayed in the Table. There were no statistically significant differences in baseline characteristics between the 2 groups. The TRT-receiving group had a significantly higher rate of potency at 2 years in comparison to the no-TRT group (63.6% vs 35.1%; Pearson X² test, P = .017; Table). Multivariate regression analysis showed that TRT was a predictor of potency outcomes 2 years post RARP after adjusting for age and Gleason Grade Group (odds ratio: 3.33; 95% CI: 1.16-10.3; P = .029). There were no significant differences in potency rates between the 2 groups at time points of 3, 9, and 15 months post RARP (Figure 1). There was no significant difference in BCR rates between the 2 groups (TRT 12.1% vs no-TRT 27.0%, P = .12; Table) with a mean follow-up time of 40.2 ± 13.6 months. Kaplan-Meier analysis demonstrated a trend towards delayed time to BCR in the TRT group (P = .078; Figure 2).

Table. Patient Demographics of Testosterone Replacement Therapy vs No Treatment

The findings support the growing body of evidence suggesting that TRT may enhance erectile function recovery in hypogonadal men post RP. Informed by Morgentaler’s⁵ concept of a “saturation” level of testosterone, which posits that lower levels may still support normal erectile function, our study administered TRT to low-risk men without disease signs, aiming to optimize post-RP outcomes. This approach aligns with studies indicating that even modest testosterone levels can sustain erectile function. Moreover, insights from studies involving eugonadal men receiving testosterone supplementation underscore its potential to improve sexual activity, satisfaction, libido, and nocturnal erections.

The assessment of potency recovery in our study utilized validated measures, such as the IIEF-5 and Erection Hardness Score, emphasizing comprehensive evaluation criteria. While definitions of potency recovery vary, encompassing specific IIEF-5 scores or functional outcomes, the consistent improvement seen with TRT underscores its clinical relevance. Additionally, the inclusion of a validated self-reported measure of “erection fullness percentage” enhanced qualitative assessments, ensuring robust patient-reported outcomes and high participation rates.

In conclusion, TRT significantly improved potency outcomes 2 years post RP in hypogonadal men aged 60 and older. While the study suggests a lower risk of BCR in TRT recipients, statistical significance was not achieved, necessitating further investigation with larger cohorts and extended follow-up. These findings advocate for the judicious use of TRT in carefully selected patients post prostatectomy, emphasizing its potential to enhance quality of life without compromising oncological outcomes. Our study contributes valuable insights into optimizing postprostatectomy care, urging continued research to refine TRT guidelines and validate long-term safety and efficacy profiles. Future prospective studies are essential to corroborate these findings and establish definitive recommendations for TRT use in this clinical context, addressing ongoing controversies and enhancing patient outcomes.