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Prostate Cancer
Testosterone and Prostate Cancer
a report by
Vincenzo Mirone
Professor of Urology, University Federico II, Naples
Although numerous studies and much attention have been dedicated to a substantial proportion of men for whom testosterone is prescribed
the study of the potential relationship between prostate cancer and already harbour prostate cancer, and altering hormonal status by giving
testosterone levels, the actual physiopathological interaction between the exogenous testosterone may stimulate these cancers.
two remains largely unclear. The sensitivity of prostate cancer to
testosterone, first noted by Huggins and Hodges, is now well established, The majority of cancers in our study were diagnosed within the first two
and the use of testosterone ablation or blockade for palliation of years of testosterone administration and 35% were diagnosed within the
disseminated disease is widely accepted. The disease flare that can follow first year, suggesting that exogenous androgens stimulated cancers that
administration of luteinising hormone-releasing hormone agonists, which were present, if unrecognised, at the time of testosterone initiation.
temporarily stimulate androgen production unless an antiandrogen is Many other studies have examined exogenous testosterone replacement
given, is further evidence that advanced prostate cancer is stimulated by in hypogonadal and eugonadal men, and its effects on serum PSA.
androgens. However, little is known about the ability of exogenous
testosterone for androgen deficiency to stimulate occult prostate cancer In one systematic review, testosterone replacement therapy (TRT) in
or increase the risk of prostate carcinogenesis. hypogonadal men was associated with a significant increase in serum
PSA by 0.68 standard deviations from baseline, which corresponds to an
Prostate Cancer Detection in Men Using average increase in serum PSA of 3ng/ml in young patients, and a PSA
Testosterone Supplementation increase of 0.48ng/ml in older patients. Overall data suggest that
The limited literature suggests that the risk of testosterone replacement administration of testosterone to men with androgen deficiency can be
stimulating occult prostate cancer is relatively small. A recent review of expected to produce modest increases in serum PSA, generally less than
several prospective studies investigating the incidence of prostate cancer 0.5ng/ml, and that increases greater than 1ng/ml are unusual.
in men receiving testosterone supplementation identified only five among
461 men observed from six to 36 months (1.1%). This prevalence rate is Recent Evidence for the Relationship between Prostate
similar to that of the general population. Of greatest concern is the high Cancer and Testosterone Plasma Levels
prevalence of subclinical prostate cancer and how testosterone A history of prostate cancer has always been considered an absolute
supplementation might affect these tumours. contraindication for testosterone supplementation. Although our
understanding of the relationship between androgens and the
Autopsy studies have confirmed that approximately 35% of men have development of prostate cancer is still evolving, current data demonstrate
occult prostate cancer and a 14% incidence of occult cancer was found a similar risk (approximately 1%) of prostate cancer in men treated with
in hypogonadal men who were candidates for testosterone therapy. In or without testosterone supplementation.
the recent Prostate Cancer Prevention Trial (PCPT) study investigating the
chemoprevention potential of finasteride, prostate cancer was found in Testosterone replacement therapy is now being prescribed more often
15.2% of men in the placebo group who had normal digital rectal for ageing men – the same population in which prostate cancer
examination (DRE) results and prostate-specific antigen (PSA) levels. If incidence increases – and it has been suggested that administration in
PSA was 3–14ng/ml, 27% had prostate cancer, and 25% of these men with unrecognised prostate cancer might promote the
cancers were Gleason sum 7 or greater. These reports clearly indicate that development of clinically significant disease. The hypothesis that high
levels of circulating androgens are a risk factor for prostate cancer is
supported by the dramatic regression, after castration, of tumour
Vincenzo Mirone is Professor of Urology and Director of the
Post-graduate School of Urology at Federico II University,
symptoms in men with advanced prostate cancer. However, these
and Head of the Urology Unit at Federico II Hospital in
effects, seen at a very late stage of cancer development, may not be
Naples, Italy. He is President of the Italian Society of
Urology (SIU), Chair of the European Society of Andrological
relevant to the effects of variations within a physiological range at an
Urology (ESAU), Full Member of the European Association of earlier stage. Data from all published prospective studies on the
Urology (EAU) Section Office, Chair of the Italian section of
circulating levels of total and free testosterone (TT and TF) do not
the European Sexual Dysfunction Alliance (ESDA), Full
Member of the Association of Academic European
support the hypothesis that high levels of circulating androgens are
Urologists (AAEU) and an active member of many European urological societies. He is a
associated with an increased risk of prostate cancer.
referee for European Urology and the International Journal of Andrology and the author of
more than 490 papers and chapters on urological and andrological subjects with more than
68 original articles indexed in the National Library of Medicine. He has also been awarded A study on a large prospective cohort of 10,049 men has contributed to
several prizes by the International and National Medical Congress.
the gathering evidence that the long-standing ‘androgen hypothesis’ of
increasing risk with increasing androgen levels can be rejected,
26 © TOUCH BRIEFINGS 2007
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