Testosterone and Prostate Cancer: An Historical Perspective on a Modern Myth

ObjectivesTo review the historical origins and current evidence for the belief that testosterone (T) causes prostate cancer (pCA) growth.MethodsReview of the historical literature regarding T administration and pCA, as well as more recent studies investigating the relationship of T and pCA.ResultsIn 1941 Huggins and Hodges reported that marked reductions in T by castration or estrogen treatment caused metastatic pCA to regress, and administration of exogenous T caused pCA to grow. Remarkably, this latter conclusion was based on results from only one patient. Multiple subsequent reports revealed no pCA progression with T administration, and some men even experienced subjective improvement, such as resolution of bone pain. More recent data have shown no apparent increase in pCA rates in clinical trials of T supplementation in normal men or men at increased risk for pCA, no relationship of pCA risk with serum T levels in multiple longitudinal studies, and no reduced risk of pCA in men with low T. The apparent paradox in which castration causes pCA to regress yet higher T fails to cause pCA to grow is resolved by a saturation model, in which maximal stimulation of pCA is reached at relatively low levels of T.ConclusionsThis historical perspective reveals that there is not now—nor has there ever been—a scientific basis for the belief that T causes pCA to grow. Discarding this modern myth will allow exploration of alternative hypotheses regarding the relationship of T and pCA that may be clinically and scientifically rewarding.