Questioning the evidence behind the Saturation Model for testosterone replacement therapy in prostate cancer

Published in 2009, the Saturation Model suggested that there were limits to which androgen encouraged growth of the prostate. This was, in particular, applied to prostate cancer, where conventional wisdom since Huggins has considered it almost taboo for a patient being treated with cancer to receive testosterone replacement therapy (TRT). Since then, several studies began to investigate the application of TRT in, at first, mild and stable prostate cancer patients. While early reports seem promising, the validity of the Saturation Model had not been addressed. The current review investigates the evidence synthesis behind the Saturation Model, based on its original publication where it was presented. The evidence reviewed includes in vitro, in vivo and clinical studies that were referenced as the basis when the model was presented. Despite promising associations, the evidence employed were troublingly taken out of context in many cases and applied freely in cases where it would be unwise to do so. In light of some shortcomings in evidence synthesis, we advise some caution when applying the Saturation Model in prostate cancer.