ORIGINAL RESEARCHAndrogen Replacement in Men Undergoing Treatment for Prostate Cancer
Introduction
Hypogonadism is a clinical and biochemical syndrome characterized by typical signs and symptoms and low serum testosterone levels, which may cause significant detriment in the quality of life and adversely affect the function of multiple organ systems. Long-term testosterone replacement therapy (TRT) has been shown to have positive effects on sexual function, mood, bone mineral density, and body mass [1]. Restoring testosterone levels to normal in men with proven subnormal testosterone levels improves libido in most subjects, and erectile function in more than 50% of these men 2, 3, 4.
Testosterone deficiency syndrome (TDS) causes a wide range of symptoms that can lead to significant morbidity. Preliminary evidence has also linked TDS with premature mortality and with a number of comorbid diseases including diabetes and metabolic syndrome. Such associations can lead to substantial economic and quality of life implications 5, 6, 7.
The main concern regarding TRT for hypogonadal men is the not completely understood relationship between testosterone and prostate cancer (PCa). Since Huggins [8] first described that castration caused regression of metastatic PCa, there has been much debate regarding the association between testosterone and PCa. First, it was hypothesized that men with higher endogenous levels of testosterone would carry a greater risk of PCa. Although most of the studies 9, 10, 11, 12, 13, 14 have not found a correlation of serum testosterone with future development of PCa, two studies 15, 16 demonstrated a positive correlation between androgen levels and PCa, and suggested a potential implication regarding TRT and the risk of developing PCa in this situation. Subsequently, it was suggested that TRT could increase the risk of PCa; however, the rate of PCa in trials of men submitted to androgen supplementation was similar to that of the general population [17]. Morgentaler et al. [18] determined the prevalence of occult PCa in men with low serum total or free testosterone levels. A retrospective analysis of a consecutive series of men was carried out. Seventy-seven men with low serum total or free testosterone levels, with normal results of digital rectal examination (DRE) and prostate-specific antigen (PSA) levels of 4.0 ng/mL or less, were included. The mean age was 58 years (36 to 81 years). The patients underwent sextant prostate needle biopsies with ultrasound guidance. PCa was identified in 14% (11/77) of the entire group and in 10 men (29%) aged 60 years or older. Although there are concerns about the validity of the analogue free testosterone assay used in this report, this study is an important contribution for a better understanding of testosterone and PCa relationship.
More recently, in the Prostate Cancer Prevention Trial (PCPT) study that investigated the chemoprevention potential of finasteride, PCa was found in 15.2% of men in the placebo group who had normal DRE results and PSA levels. The incidence of PCa in Morgentaler's report appears to be similar to the incidence observed in the control group of the PCPT trial. However, it is important to emphasize that the mean age in Morgentaler's study was lower than in the PCPT study (58 years vs. 69 years, respectively).
The purpose of this article is to review the available literature regarding this controversial issue: TRT after PCa treatment.
Section snippets
Testosterone Replacement after Treatment for PCa
The Food and Drug Administration states that TRT is contraindicated in men with known or suspected PCa, but does not substantiate this contraindication. In its clinical practice guideline, the Endocrine Society recommends against starting testosterone therapy in men with PCa, but recognizes that the available evidence supporting this contraindication is of very low quality [19].
It has been observed in animal models that increases in plasma testosterone levels positively correlate to growth of
Discussion
The risk of clinical PCa in men receiving testosterone replacement is not known. To date, clinical trials have only included a few hundred men, and these studies have not been powered to address the risk of clinical PCa. None of the randomized placebo testosterone trials have required prostate biopsies either at the start or at the end of the study. Therefore, the prevalence and incidence of occult PCa was not addressed. A compilation of published prospective studies of TRT revealed only five
Conclusion
There is accumulating evidence attesting the safety and effectiveness of testosterone replacement in hypogonadal men. Yet, further studies are necessary before definitive conclusions regarding the use of TRT in men treated for PCa can be drawn. Although scant, the available data suggest that TRT can be cautiously considered in selected hypogonadal men previously treated with curative intent for low-risk PCa and without evidence of active disease. However, one must remember that the small series
Category 1
- (a)
Conception and Design
Ernani Luis Rhoden; Márcio Augusto Averbeck; Patrick E. Teloken
- (b)
Acquisition of Data
Ernani Luis Rhoden; Márcio Augusto Averbeck; Patrick E. Teloken
- (c)
Analysis and Interpretation of Data
Ernani Luis Rhoden; Márcio Augusto Averbeck; Patrick E. Teloken
Category 2
- (a)
Drafting the Article
Ernani Luis Rhoden; Márcio Augusto Averbeck; Patrick E. Teloken
- (b)
Revising It for Intellectual Content
Ernani Luis Rhoden; Márcio Augusto Averbeck; Patrick E. Teloken
Category 3
- (a)
Finial Approval of the Completed Article
Ernani Luis
Acknowledgment
Dr. Rhoden is a researcher of the National Counsel of Technological and Scientific Development (Conselho Nacional de Desenvolvimento Cientifíco e Tecnológico)—Brazil.
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Cited by (0)
Conflict of Interest: None declared.