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?