INTRODUCTION: Is there any unequivocal evidence that testosterone (T) can stimulate growth and aggravate symptoms in men with locally advanced and metastatic prostate cancer (PCa)? This is not a controversial point: the answer is yes. However, this evidence does not imply that PCa is a result of T or therapy with T (TTh) of hypogonadal men. Furthermore, currently adequately powered and optimally designed long-term prostate disease data are not available to determine if there is an additional risk from normal T values in cured patients for PCa. METHODS: This Controversy is introduced by an endocrinologist, the section editor (E.A.J.) with G.L.G., a fellow urologist and radiotherapist expert in basic research on PCa. Two outstanding urologists, A.M and W.J.G.H., debate clinical data and clinical guidelines, respectively. Finally, other controversial issues are discussed by another leader in the field (A.M.) and a radiation oncologist and sexologist who is actually president of the International Society for Sexuality and Cancer (L.I.). MAIN OUTCOME MEASURE: Expert opinion supported by the critical review of the currently available literature. RESULT: The answer to the main question "is the prostate a really T-dependent tissue?" is definitively yes, but T stimulates the prostatic tissue in a dose-dependent fashion only to a saturation point, achieved at low T concentrations. At these low T concentrations, stimulation is near maximal, and T supplementation above this level would not lead to significantly greater stimulation. Furthermore, there is no conclusive evidence that TTh increases the risk of PCa or even prostatic hyperplasia. There is also no evidence that TTh will convert subclinical PCa to clinically detectable PCa. However, there is a limited clinical experience of TTh after successful treatment of PCa. So far, just 48 patients have been studied in the three published articles. CONCLUSIONS: It is evident that the issue is still controversial and much more research is needed. However, the available data suggest to the expert in sexual medicine that TTh can be cautiously considered in selected hypogonadal men previously treated for curative intent of low-risk PCa and without evidence of active disease.
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