Testosterone Therapy in Patients with Treated and Untreated Prostate Cancer: Impact on Oncologic Outcomes: Beyond the Abstract

The use of Testosterone Therapy (TT) in men diagnosed with and treated for prostate cancer (CaP) has been highly controversial for several decades. Unfortunately, this controversy is largely founded on the results of a single patient in a study by Huggins and Hodges in the 1940s [1].

This wasn't challenged until 2006, when Morgentaler reviewed the literature on the topic and found that there was no scientific basis for the assumption that TT would act like fuel on the fire of prostate cancer [2]. Over the past decade, retrospective evidence has been accumulating that supports the safety of TT in hypogonadal men with CaP on Active Surveillance, or in those who have been definitively treated for CaP. 

In our study, we looked at data from 82 men, all who had received TT after treatment for prostate cancer, or during active surveillance for prostate cancer. A summary of the important findings are as follows:

Of the 82 men analyzed:

- 50 were treated with radiation therapy (37 with external beam radiotherapy, 13 with brachytherapy).

- 22 were treated with radical prostatectomy (RP)

- 8 were followed with active surveillance (AS)

- 21 of these men received neoadjuvant androgen deprivation therapy.

The median age of the men was 75.5 years. The median follow up while on TT was 41 months.

When comparing PSA and testosterone in the entire cohort before and after TT initiation:

- serum testosterone showed a significant increase in all groups (p<0.001)

- serum PSA showed a significant increase in all groups, and within each treatment group. 

Of the 22 men treated with radical prostatectomy, there were no incidences of biochemical recurrence (BCR). Of the 50 men treated with radiation therapy, there were 3 instances (6%) of BCR. 1 of these men experienced clinical progression. 

Of the 8 men treated with active surveillance:

- all patients had low volume Gleason 6 disease.

- no patients were upgraded to higher Gleason score on repeat biopsy.

Analyzing background literature shows that our rate of BCR is lower than what is reported in large trials of radiation therapy [3] and radical prostatectomy [4]; albeit our follow up isn't as long as those studies.

From our results, we see that in hypogonadal men with a history of treated or untreated prostate cancer, testosterone therapy resulted in an increase in testosterone and a small but significant increase in PSA. These findings are similar to what is seen in other, similar studies. 

The length of follow up and number of patients makes our study unique in its support of the safety of testosterone in this patient population. However, there exists a baseline rate of progression and/or biochemical recurrence in all men with prostate cancer, and until a randomized, placebo controlled study has been performed, we cannot make any definitive statements on how testosterone may or may not influence that rate. In the absence of a high quality RCT, our study supports the hypothesis that testosterone therapy may be oncologically safe in hypogonadal men after definitive treatment or in those on active surveillance for prostate cancer. 

Written by: Jesse Ory 


1. Huggins C and Hodges CV: The effect of castration, of estrogen and of androgen injection on serum phosphatase on metastatic carcinoma of the prostate. Cancer Res 1941; 1: 293

2. Morgentaler A: Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol 2006; 50: 935.

3. Zumsteg ZS, Spratt DE, Romesser PB et al: The natural history and predictors of outcome following biochemical relapse in the dose escalation era for prostate cancer patients undergoing definitive external beam radiotherapy. Eur Urol 2015; 67: 1009.

4. Pastuszak AW, Pearlman AM, Lai WS et al: Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. J Urol 2013; 190: 639.

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