The historic “prohibition” against the use of testosterone therapy in men with a history of prostate cancer is based on a model that assumes that the androgen sensitivity of prostate cancer extends throughout the range of testosterone concentrations.
Morgenthaler is a well-known advocate for the use of testosterone in at least some patients with a known history of prostate cancer and androgen deprivation therapy (ADT). In developing a recent review, Morgenthaler performed a literature search of English language publications on testosterone administration in men with a known history of prostate cancer and synthesized the data from all appropriate and relevant publications.
Based on the literature review, the author starts from the position that prostate cancer is exquisitely sensitive to changes in serum testosterone at low concentrations, but that there is considerable evidence that prostate cancer growth becomes androgen indifferent at higher concentrations. He suggests that the most likely mechanism for this loss of androgen sensitivity at higher testosterone concentrations is the limited capacity of androgen receptor molecules to bind androgen.
There is no doubt that this saturation model can be used to explain why serum testosterone appears unrelated to prostate cancer risk in the general population, and why testosterone administration in men with metastatic prostate cancer causes rapid progression in castrated but not hormonally intact men. Morgenthaler goes on to point out that worrisome features of prostate cancer such as high Gleason score, extracapsular disease, and biochemical recurrence after surgery have been reported in association with low testosterone levels. However, he states that there is no evidence of such problems in the case of patients with high testosterone levels.
According to the author, based on his literature review, there have been a total of six uncontrolled studies in which results of testosterone therapy have been reported after radical prostatectomy, external beam radiation therapy, or brachytherapy. He states that in a total of 111 men, there have been just two cases (1.8 percent) in which biochemical recurrences were observed. He also argues that anecdotal evidence suggests that testosterone therapy does not necessarily cause increased PSA levels, even in men with untreated prostate cancer.
Finally, Morgenthaler notes that there have been no controlled studies (to date) to document the safety of testosterone therapy in men with prostate cancer. He goes on to take the position that the limited available evidence suggests that such treatment may not pose an undue risk of prostate cancer recurrence or progression.
The “New” Prostate Cancer InfoLink is of the opinion that there is only one way to resolve this issue, which is through the use of appropriately controlled and blinded studies in a carefully selected and stratified patient group (or groups). We neither reject nor do we accept Morgenthaler’s premise. We think it needs to be tested in the “real world.” The critical issue, it seems to us, is as follows: if there is a risk to the use of testosterone therapy in men with prostate cancer, how big is that risk and what are the potential consequences of that risk for individual patients?
Filed under: Living with Prostate Cancer, Management, Treatment Tagged: | androgen sensitivity, testosterone therapy
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As a 64-year-old man, treated for prostate cancer 6 years ago with brachytherapy + external beam radiation, I am very interested in this question. Currently my testosterone levels are low, and I am experiencing the consequent symptoms (fatigue, depression, fragile emotions, memory, focus issues, etc). My current PSA is 0, and has been for 2 years. The issue of a “lurking” cancer cell just waiting for testosterone to kick off growth has been raised. I am in a quandry about what to do ….
Interested in following this thread!
I am in similar situation: 75 years old, low T (332 ng; 37 pg) following IMRT 4 years ago; PSA 0.112 (never higher); symptoms of low T; want replacement therapy but no willing physician. Also, ADT treated at castrate level for 1 year in conjunction with IMRT. Interested in latest results of any trials or recommendations for T therapy to improve quality of life.
Jim K.
Dear Jim K:
I have to tell you that I know of know data to even begin to suggest that testosterone therapy would be wise for a man like you. The risk that it would re-stimulate the growth of any tiny number of cancerous cells not killed off by radiation therapy is too high.
I suppose you might be able to find a physician who would prescribe testosterone supplements … but it wouldn’t be any physician who had sound knowledge about prostate cancer.
Would you care to address the following: According to the author, based on his literature review, there have been a total of six uncontrolled studies in which results of testosterone therapy have been reported after radical prostatectomy, external beam radiation therapy, or brachytherapy. He states that in a total of 111 men, there have been just two cases (1.8 percent) in which biochemical recurrences were observed. He also argues that anecdotal evidence suggests that testosterone therapy does not necessarily cause increased PSA levels, even in men with untreated prostate cancer.
Jim:
The actual incidence of recurrence of prostate cancer in men with a well-documented history who were subsequently treated with testosterone supplementation is in itself an area of controversy. This is inherently one of the problems. There has never been a large, really well-documented, prospective study of the use of testosterone supplementation in patients with a histroy of prostate cancer, so the real risks are very ill-defined.
It is clear that the risk may not be anything like as high as people used to think it was, but my personal suspicion is still that it is a great deal higher than 1 to 2 percent.
Thank you for your interesting comments and web site. I will stay tuned. Haven’t given up on the idea of T supplementation.
I am 69 years old and 8+ years post open radical prostatectomy at M. D. Anderson. I had an original Gleason of 3 + 4 = 7. I also had two areas of positive margins. I went for 5 years with an undetectable PSA after surgery when it started to come back. I then had 2 months of salvage radiation in 2010. My PSA has been undetectable since radiation.
My last serum testosterone level was 245 ng/dl. I had a recent penile implant (again at M. D. Anderson). Question: Would anyone suggest supplemental testosterone with positive margins and recurrence at 5 years?
Dear Lou:
I am sure that if you hunted hard enough you would be able to find a physician who would prescribe supplemental testosterone therapy for you if you were determined to get this. However, I have to say that most urologists would probably not think this was wise in a case like yours. At the end of the day, these are very personal decisions, and the available data show that some men can have supplemental testosterone therapy with apparently minimal risk, whereas others (somewhere between 30% and 50%) will see their PSA start to rise again.
I am assuming that you have discussed this with your doctors at M. D. Anderson. I am also assuming that they are telling you much the same as what I have written above. Alas, we really don’t have good enough data yet to be able to tell a specific man that supplemental testosterone would or would not be safe in a case like yours … but rolling the dice would appear to come with a high level of risk for someone like you.