Supplemental testosterone therapy in men treated for prostate cancer

The role of supplemental testosterone therapy in men previously treated for prostate cancer has long been a controversial issue, and the number of patients actually studied for the effects of such therapy (good and bad) is really quite small — at about 600 worldwide.

A new study by Pastuszak et al., published recently in the Journal of Urology, has added to our database of knowledge about the pros and cons of testeosterone supplements in men with a history of prostate cancer. What this study does not necessarily do, however, is given us much more definitive information about who is and who is not a good candidate for this type of treatment.

The authors looked at data from a series of patients, all of whom were initially treated at their institution by radical prostatectomy for localized prostate cancer, but only some of whom subsequently went on the be treated with testosterone for hypogonadism (low testosterone levels).

Readers need to be very clear in interpreting the results of this study that it comes with a number of inherent structural problems and limitations:

  • It is a retrospective analysis, not a randomized, prospective trial.
  • The men who did not receive testosterone replacement therapy (TRT) were screened for but never formally evaluated for hypogonadism.
  • Median follow-up times in this study are still relatively short.

So with these provisions, here are the key findings presented by the research team:

  • 103 men received a radical prostatectomy and subsequently received TRT (Group A).
    • 26/103 men had high-risk disease.
    • 77/103 men had low- or intermediate-risk disease.
  • 49 men received a radical prostatectomy and no subsequent TRT (Group B).
    • 15/49 men had high-risk disease.
    • 34/49 men had low- or intermediate-risk disease.
  • More cases of T3b tumors were found in Group B (6/49, 12 percent) than in Group A (2/103, 2 percent).
  • For the men in Group A
    • Average (median) follow-up was 27.5 months (range, 6.2 to 189.3 months).
    • Median time to initiation of TRT was 12.3 months after surgery.
    • Biochemical recurrence of prostate cancer was observed in 4/103 patients (all of whom were high-risk patients).
    • Significant increases in serum T levels were evident at almost all follow-up evaluations.
    • Increases in serum T levels were not evident in the men with high-risk disease at median follow-up.
    • There was a small increase in serum PSA levels at 18 to 24 months after initiation of TRT (among men with high-risk and men with low/intermediate-risk disease).
    • Median PSA velocity was 0.002 ng/ml/yr.
  • For the men in Group B
    • Median follow-up was 16.5 months (range, 1.7 to 77.0 months).
    • Biochemical recurrence of prostate cancer was observed in 8/49 patients (all of whom were high-risk patients).
    • There was no increase significant in serum PSA levels at any time.
    • Median PSA velocity was 0.0002 ng/ml/yr.

The authors reach the following conclusions in evaluating their results:

  • Their data do not suggest that treatment of hypogonadism can lower the rate of recurrence of prostate cancer post-surgery.
  • Conversely, their data do support the use of TRT in patients with prostate cancer who are hypogonadal post-surgery but only in a rigorously monitored scenario.
  • Prospective studies with a larger number of patients and longer-follow-up are essential if we are to be able to come to more practicable conclusions about the appropriate use of TRT in hypogonadal patients post-surgery.

There is additional discussion of this study in a commentary on the Medscape web site.

13 Responses

  1. I’m one year into active surveillance, and am continuing my TRT. I know it’s not the same as the article (I’m pre-treatment), but I wanted to mention it in case there are others like me out there, looking to continue their life as best they can as regards an important hormone!

  2. My understanding from previous research, that with apologies I cannot track right now, is that there is a threshold level of serum testosterone (T) around 150 ng/dl over which TRT has no impact. If a man has prostate cancer and a serum T 150, then TRT has little impact.

    In my own case, I started supplementing T with Androgel just under a year ago, about 18 months after I finished 27+ months of Lupron; my serum T level had returned to pre-Lupron levels then dropped about 20%. I felt weak and my sleep was poor, so my urologist suggested TRT. While it has not moved my serum T level, I do feel better for it. More pertinent to this discussion, it has not appeared to compromise my PSA.

  3. Dear Rick:

    I would want to know the evidence from the prior research you refer to. A lot of theoretical analysis has led to a number of equally theoretical propositions with very little meaningful evidence to support these propositions because the studies were very small and retrospective in nature.

  4. Yeah, I’d doubt that as well. TRT should always have a positive effect, if done correctly.

  5. I will try to track the study down … but Walt — I can tell you that my TRT has not increased my serum T.

    By the way my original comment should read: “If a man has prostate cancer and a serum T greater than 150, then TRT has little impact” — on the prostate cancer, that is.

  6. I recently read the book Why Men Fake It by Dr. Abraham Morgentaler, a Harvard-affiliated doctor who is probably best known for treating men with low testosterone. In this book, he briefly discusses the effect of testosterone on prostate cancer, and he has come to the conclusion that while prostate cancer requires a minimal amount of testosterone to grow, additional testosterone has no effect on the cancer. Here is a quote from the book:

    “In May 2011 I published with my colleagues Larry Lipschultz, MD, and Mohit Khera, MD, from Baylor Medical College, a report in the Journal of Urology on thirteen men with untreated prostate cancer who received testosterone therapy for an average of two and a half years. They had an average of two sets of follow-up prostate biopsies. None of the men showed any progression of their cancers, and in 54 percent of the biopsies we couldn’t find a trace of the cancer that had been there earlier. It was a small study, so we must be careful not to overstate the conclusions; however, this was the very first time since Huggins in 1941 that anyone had bothered to look directly at what actually happens to an existing localized prostate cancer when a man receives testosterone treatment. The answer appears to be: ‘Not much.’ I’ve since treated many more of these men, with similar, good results.”

  7. Unfortunately, to date, others have not been able to replicate the results claimed by Dr. Morgentaler with quite the same level of safety.

    There is no doubt that some men who have previously been diagnosed with prostate cancer can be treated with testosterone with minimal risk for progression of their cancer. On the other hand, it is certainly the case that this doesn’t apply to all patients, and we are still trying to work out how to tell which men can be treated safely and which men are at significant risk for progression after testosterone therapy.

  8. His success seems even better with untreated guys (like me) who continue on with TRT under active surveillance. The follow-up biopsies put the old testosterone-based theories about prostate cancer in a rather bad light.

    His patients’ data actually correlate low testosterone as a higher-risk group for positive biopsies. The old theories are horribly flawed.

    My yearly biopsy was a great success: less volume (2/12), and a Gleason 3 + 3. I was thrilled!

  9. Dear Walt:

    It is important to understand that the “old” testosterone theories about prostate cancer were developed (and subsequently shown to be accurate) exclusively in men with progressive, metastatic prostate cancer. We know now that this is only a relatively small subset of all the men who are found to have some prostate cancer cells in their prostates.

    Huggins and his colleagues probably never saw (let alone treated) a man with characteristics like yours. Men like you just didn’t get diagnosed back in the 1940s. From that perspective, the good Dr. Morgantaler isn’t exactly comparing apples to apples!

    So long as he sticks to giving low-dose TRT to men with low-risk prostate cancer and hypogonadism who need TRT to “up” their energy levels and their libido, there’s probably no significant problem. The problems start to arise when men with higher-risk disease get TRT or men with low-risk disease are given higher doses of TRT.

  10. Of course, you are correct. I thought about that after I hit “send”, and went to the bathroom. I remembered I left out too many details that are required for an accurate assertion in that regard.

    It’s such an immense topic. I cannot believe how much I have learned since May 2012!! Thanks for running such a great site for us gents.

    PS: I think all (most?) doctors administering TRT are judicious. I know I’ve always had blood tests every 3 months to check testosterone levels.

  11. [Editor: The following is a series of five originally disconnected comments provided by HMM. It is less than clear to your Sitemaster what point or points he is trying to make.]

    Comment A:

    Morgantaler has something like … 4 or 5 publications in JAMA or urology journals … plus, several interviews.

    I wouldn’t go to his book Why Men Fake It … at least per se.

    Besides, his 54% is just about what I previously surmised … 50-50 chance you aren’t going to see anything after a RP or at least no “progression”. (How did he determine that? PSA velocity above a specific level? Over what time period?)

    I assume he was looking at men who had had a RP (my assumption).

    Comment B:

    LabCorp suggest that the normal baseline for serum testosterone begins at around 350.

    Most research studies classify a lower quartile reading as being below 250.

    Comment C:

    In most research studies, the lowest quartile for males is “roughly” something below 250.

    The individual who suggested his 150 level was “normal” is talking to the wrong doctor.

    One example: a paper by Lauglin GA, et al. entitled “Low serum testosterone and mortality in older men” (which has been cited by other articles listed in PMC).

    Comment D:

    The sitemaster is somewhat mixing apples and oranges here in interpreting the findings of this study …

    • “Their data do not suggest that treatment of hypogonadism can lower the rate of recurrence of prostate cancer post-surgery.”

    The argument in urology is that increasing testosterone will raise the probability …. It has never been (to my knowledge) that it will lower it.

    Comment E:

    “… a relatively small subset …”?

    Do your research. … This type of comment is a fallacy — perpetuated by the recent PR release by the “Academy” and a tragedy for those who think their chances are remote for having an aggressive prostate cancer.

  12. ADT therapy for males with prostate cancer (triple blockade) is typically (almost universally) prescribed to lower testosterone and DHT. The thesis is that low testosterone and DHT levels will reduce the probability of recurrence of the cancer (whether continuous or intermittent ADT). Therefore, testosterone therapy is contra-indicative of traditional ADT hormonal therapy protocols.

    Traditionally, increasing the rate of Test is counter productive — whether hypo or not.

    Therefore, in conclusion (assuming quite a bit about the study controls), to me TRT therapy for RP males is questionable (cohort B is extremely small in number), or shall we say “slightly more effective than non-TRT” given the distribution of risk within the cohorts..

    Furthermore, we have no idea if the researchers stratified testosterone levels based on age, which would really influence the interpretation of the results.

  13. HMM:

    Your comments are not relevant to pre-treatment, low-risk, low-volume prostate cancer patients. … Just sayin’.

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