Effect of testosterone administration to men with prostate cancer is unpredictable: a word of caution and suggestions for a registry

Abstract

What’s known on the subject? and What does the study add? Very little is known on the effect of T in men with untreated PCa. There are only two small series (including the present one) available that comprise less than 25 men with PCs receiving TTh. It raises a warning that testosterone administration to men with PCa is not always safe, that current precautions should be maintained, and that only an international registry would provide prompt answers to these issues. To assess the evidence for the concept that the androgen receptor of prostate cancer (PCa) cells becomes saturated when testosterone values exceed castrate levels, so that testosterone administration in hypogonadal men with untreated PCa does not stimulate tumour growth. To propose basic criteria for administration of testosterone to untreated patients with PCa and, as this is a rare clinical situation, to encourage the establishment of an international registry for these patients. Men with a diagnosis of PCa and symptomatic testosterone deficiency received testosterone therapy (TTh). Patients were assessed quarterly. Prostate‐specific antigen (PSA) velocity was used as the criterion to discontinue therapy and a return to nadir PSA levels allowed re‐initiation of testosterone supplementation. The responses to testosterone supplementation were varied according to each individual and were unpredictable. While some men showed little change after years of treatment, others exhibited a rapid and significant increase in PSA levels. In others, the use of intermittent therapy resulted in synchronous changes in PSA levels. Interruption of TTh invariably translated into a decrease in PSA to pre‐therapy levels. Available evidence regarding the effect of testosterone administration to hypogonadal men with untreated PCa is too limited to be considered reliable. In addition, the response to this treatment appears to be varied and unpredictable. Hypogonadism associated with untreated PCa is not common, therefore, we propose the establishment of an international registry as the quickest way to establish the basic parameters for consideration of TTh in this situation and recommendations for follow‐up. Until credible evidence becomes available, the current restrictions regarding the administration of testosterone to men with PCa should remain in place.

Testosterone Replacement Therapy in Hypogonadal Men Following Prostate Cancer Treatment: A Questionnaire-Based Retrospective Study among Urologists in Bavaria, Germany

“…Morgentaler et al [32] observed 13 patients with known PCa, who were treatment naïve and had clinically significant hypogonadism during TRT for a median of 2.5 years, and did not find a single example of local or systemic progress. Morales [33] reported on 7 men with untreated PCa and hypogonadism on TRT, 5 of whom had low-risk disease. The report describes 4 different PSA scenarios, 1 stable course and 3 distinct profiles of progression.…”

“…The report describes 4 different PSA scenarios, 1 stable course and 3 distinct profiles of progression. Thus, Morales [33] advises others to be cautious and advocates for an international registry to identify risk factors relevant for hormonal treatment in men with PCa. The guidelines of the European Association of Urology [34] on male hypogonadism see PCa as a contraindication for testosterone substitution.…”

Testosterone deficiency in the aging male

“…Likewise, limited reports of testosterone use in hypogonadal men on active surveillance protocols appear promising [Morales, 2011;Morgentaler et al 2011]. Yet one must emphasize the data for TRT in men with a history of prostate cancer are without randomized or placebo controlled trials and should be interpreted with caution.…”

Addressing the pressing issues related to testosterone administration to men with prostate cancer

“…12,13 Similar observations have been reported in patients with cancers confined to the gland. 14,15 The reasons remain conjectural, but range from the effect of estrogens (due to an age-related differential) in the aromatization of testosterone on the nuclear androgen receptor (AR) and the length of the CAG repeats to the lack of prostatic uptake of exogenous testosterone. The relevant point here is that there may be substantial inter-individual responses to changes in the hormonal environment of men with PCa and we should be wary of oversimplifications and generalizations.…”

“…It is evident that only a countrywide registry would provide the power to address some of the pressing issues related to testosterone administration to men with PCa. A wider effort, such as a North American (or even better, a global registry) 15 offers a better opportunity to reach credible conclusions within a shorter time context. Randomized, placebo-controlled studies, 18 although ideal, at this time remain utopian.…”