Testosterone Replacement Therapy and the Risk of Prostate Cancer. Is There a Link?

A. Barqawi; E. D. Crawford

Disclosures

Int J Impot Res. 2006;18(4):323-328. 

In This Article

The Effect of Testosterone Replacement on PSA and Prostate Volume

Based on immunoprofile studies, there are three distinct functional compartments of the prostate epithelium.[14] The first compartment consists of androgen-independent cells that secret prostate-specific antigen (PSA) and form most of the prostate epithelium. The proliferation compartment, which primarily consists of basal cells located in the basal cell layer, regulates the differentiation of pluripotent stem cells into endocrine or secretory cells, a process that requires the presence of androgen-receptive cells.[15] The function of the third compartment, which consists of endocrine-paracrine cells, is less well defined. Based on this description, there is a relationship between testosterone levels and the proliferative potential of PSA-secretory cells, which is reflected in the mixed results of reports on the clinical correlation between testosterone and PSA levels in men with normal and pathological prostates. Several studies have demonstrated significantly lower PSA levels in hypogonadal men, while others have shown a similar trend but failed to reach statistical significance. Using a PSA level of ≥4 ng/dl and a sextant biopsy as criteria for diagnosis, Morgentaler et al.[16] suggested that men with low testosterone levels might have higher rates of undetectable occult prostate cancer. There are several difficulties in interpreting these reports, including the significant variation in volume between the studies, inaccuracies in testosterone assay, and, most importantly, the different serum testosterone cutoffs used to diagnose hypogonadism. Although TRT can increase prostate size and subsequently elevate PSA levels in hypogonadal men, the prostate size and PSA levels observed in hypogonadal men treated with TRT typically do not exceed those in untreated eugonadal individuals.[4,17,18] It is postulated that TRT normalizes the growth of the prostate by balancing the underdeveloped gland secondary to the hypogonadal state.

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