Androgens, aging, and prostate health

Abstract

Due to late onset hypogonadism (LOH), there is an increased usage of testosterone replacement therapy (TRT) in the aging male population. Since prostate is a target organ for androgens and anti-androgenic strategies are used to treat and palliate benign prostate hyperplasia (BPH) and prostate cancer (PC), the prevalence of both increases with age, the possible influence of TRT on prostate health becomes highly relevant. The present review summarizes existing data on the associations between endogenous hormone concentrations and prostate growth and concludes that circulating concentrations of androgens do not appear to be associated with the risks of development of BPH or initiation or progression of PC. The explanation for these findings relates to an apparent insensitivity of prostatic tissue to changes of testosterone concentrations within the physiological range.

Keywords: Aging; Androgen signaling; Benign prostate hyperplasia; Metabolic syndrome; Prostate cancer; Testosterone replacement therapy.

Fig. 1

Simplified illustration of AR saturation in prostate cells. Translation of a certain testosterone (T) concentration in the circulation into saturated androgen receptor (AR) in prostate cells due to conversion into the more potent AR activator dihydrotestosterone (DHT) by 5-alpha reductase (5AR), compared to a relatively inefficient binding of testosterone to AR in non-prostate cells with lower 5AR activity. In the saturated prostate cell, all ARs are bound by ligand, while, at the same serum concentration of testosterone, a proportion of ARs in other organs is still free for activation