Testosterone and prostate cancer: an historical perspective on a modern myth.
OBJECTIVE
To review the historical origins and current evidence for the belief that testosterone (T) causes prostate cancer (pCA) growth.


METHODS
Review of the historical literature regarding T administration and pCA, as well as more recent studies investigating the relationship of T and pCA.


RESULTS
In 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.


CONCLUSIONS
This 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.
Morgentaler
Abraham
A
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. amorgent@bidmc.harvard.edu
D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D015995:Prevalence; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000473:pathology*; D013739:Testosterone / Q000097:blood*
D013739:Testosterone