Testosterone therapy in men with prostate cancer: scientific and ethical considerations

Pertinent literature regarding the potential use of testosterone therapy in men with prostate cancer is reviewed and synthesized.

A literature search was performed of English language publications on testosterone administration in men with a known history of prostate cancer and investigation of the effects of androgen concentrations on prostate parameters, especially prostate specific antigen.

The prohibition against the use of testosterone therapy in men with a history of prostate cancer is based on a model that assumes the androgen sensitivity of prostate cancer extends throughout the range of testosterone concentrations. Although it is clear that prostate cancer is exquisitely sensitive to changes in serum testosterone at low concentrations, there is considerable evidence that prostate cancer growth becomes androgen indifferent at higher concentrations. The most likely mechanism for this loss of androgen sensitivity at higher testosterone concentrations is the finite capacity of the androgen receptor to bind androgen. This saturation model explains 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. Worrisome features of prostate cancer such as high Gleason score, extracapsular disease and biochemical recurrence after surgery have been reported in association with low but not high testosterone. In 6 uncontrolled studies results of testosterone therapy have been reported after radical prostatectomy, external beam radiation therapy or brachytherapy. In a total of 111 men 2 (1.8%) biochemical recurrences were observed. Anecdotal evidence suggests that testosterone therapy does not necessarily cause increased prostate specific antigen even in men with untreated prostate cancer.

Although no controlled studies have been performed to date to document the safety of testosterone therapy in men with prostate cancer, the limited available evidence suggests that such treatment may not pose an undue risk of prostate cancer recurrence or progression.