PURPOSE: For many years it was believed that higher total testosterone levels (TT) contributed to prostate cancer (PCa) development and caused rapid cancer growth.
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International guidelines consider that adequate data are not available to determine whether there is any additional risk of PCa from testosterone replacement. Numerous studies with multiple designs and contradictory conclusions have investigated the relationship between TT and the development of PCa. To establish the current knowledge in this field, we reviewed the literature regarding TT and the subsequent risk of development of PCa as well as the safety of exogenous testosterone administration to patients with a past or current history of PCa.
MATERIALS AND METHODS: A literature search was conducted using the Pub Med database to identify the published English language articles related to the relationship between TT and PCa. The free-text search was extended by adding these keywords: prostate cancer, prostatic neoplasm, testosterone, hypogonadism, recurrence, prognosis, progression and incidence. All articles dated from 1994 to 2014 dealing with TT were examined by the authors. Emphasis was given to papers that were prospective, contained observational data or were randomized controlled trials. Case reports were excluded. Articles reporting safety of testosterone replacement were selected according to patient population (under active surveillance or with history of PCa). We organized our results by the nature of the relationship between TT and PCa. First, the possible link between low TT and PCa; second, the effect of high levels, and third, the absence of any link. Finally, we summarized studies assessing the risk of the administration of exogenous testosterone in patients already diagnosed with PCa, treated or under active surveillance.
RESULTS: Forty-five articles studying the relationship between TT and PCa were selected. Eighteen reported a relationship to low TT, 17 to high TT and 10 found no relation. TT was defined according to the definition given in each article. Contradictory findings were reported. This was due, to a large extent, to the disparate methodologies used in many of the studies. The majority of the studies did not adhere to the guidelines published by professional societies concerning TT measurements: 1 of 18 studies examining low TT and PCa adhered to published guidelines, none of the 17 reporting a relationship between high TT to PCa and only 1 of 10 that didn't identify a relationship between TT and PCa adhered to measurements guided by published guidelines. Eleven papers were found examining the risk of the administration of exogenous testosterone in patients with history of PCa. Many of the studies were limited by the small size of the cohorts and duration of follow-up. However, in aggregate, this literature suggests that the risk of exogenous testosterone replacement in patients with PCa appears to be small.
CONCLUSIONS: The relationship between TT and PCa has been an area of interest among physicians for decades. Conflicting results regarding the relationship between TT and subsequent PCa have been reported. Much of this controversy appears to be based in conflicting study designs, definitions and methodologies. To date, no prospective study with sufficient power has been published to unequivocally resolve the issue. The preponderance of studies examining the safety of exogenous testosterone administration in men with a history of PCa would suggest that there is little, if any risk, in such a circumstance. However, the risk has not been proven to be zero, so the most prudent course is to follow such men with regular PSAs and digital rectal exams.
Klap J, Schmid M, Loughlin KR. Are you the author?
Division of Urologic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Reference: J Urol. 2014 Sep 23. pii: S0022-5347(14)04490-5.