Differing levels of testosterone and the prostate: a physiological interplay

Abstract

The controversies surrounding testosterone replacement therapy (TRT) have been addressed in the past few years. Although the androgenic effects of TRT on normal and malignant prostate cells have been studied for over 70 years, little clinical prospective research exists on the physiological responses of prostate tissues to a wide range of serum testosterone levels. The prostate is both an androgen-dependent and an androgen-sensitive organ; active processes are triggered at a 'threshold' or 'saturation' level of testosterone. Despite decades of research, no compelling evidence exists that increasing testosterone beyond this threshold level has a causative role in prostate cancer, or indeed changes the biology of the prostate. Testosterone deficiency has marked physiological and clinical effects on men in middle age and beyond. With subnormal testosterone levels, the potential positive benefits of TRT on factors such as muscle mass, libido or erectile function are likely a dose-response phenomenon, and should be considered differently than the threshold influence on the prostate. This Review will re-examine classic androgen research and reflect on whether testosterone actually stimulates prostatic cellular growth and progression in a 'threshold' or a 'dose-response' (or both) manner, as well as discuss the influence of testosterone on prostate cells in the hypogonadal and eugonadal states.

Androgens, diabetes and prostate cancer

“…An increase of circulating androgens above a certain threshold will saturate the AR, so that the prostate will no longer respond to further increases in circulating levels of androgens above this saturation point. Conversely, below a certain lower androgen threshold, the 'castrate' level, the androgenic response will decrease, consistent with the therapeutic effect of ADT on established PCa (Morgentaler & Traish 2009, Goldenberg et al 2011. While there is experimental evidence to support such a model reviewed elsewhere (Morgentaler & Traish 2009, Goldenberg et al 2011, the saturation model is not yet proven and more research is needed.…”

“…For example, several, but not all (Salonia et al 2011) cross-sectional, studies have suggested that low testosterone levels at the time of PCa diagnosis is associated with more aggressive disease, for review see Goldenberg et al (2011) andMorgentaler (2011). Low testosterone levels have also been linked to more advanced PCa stages, and more aggressive phenotypes in radical retropubic prostatectomy specimens (Goldenberg et al 2011).…”

Testosterone Replacement Therapy in Hypogonadal Men Following Prostate Cancer Treatment: A Questionnaire-Based Retrospective Study among Urologists in Bavaria, Germany

“…The prostate is both an androgen-dependent and an androgen-sensitive organ, and active processes are triggered at a threshold or saturation level of testosterone [14] . Normal prostate development is androgen dependent, requiring not only testosterone, but also the activity of the 5α-reductase enzymes which convert testosterone to the more potent androgen dihydrotestosterone (DHT) [15] .…”

Stimulation of a non-functioning pituitary macroadenoma after administration of goserelin acetate for locally advanced prostate cancer causing a sustained elevation in PSA and testosterone

“…Recent evidence has suggested this does not have a negative impact on prostate cancer progression. 10,11 The initial treatment plan was to use the LHRH analogue, goserelin acetate. However, with this treatment serum testosterone rose unexpectedly to 15.8 nmol/L and continued to rise to 17.8 nmol/L after 3 months.…”