Prostate diseases--role of sex steroids and their inhibitors

The normal prostate as well as prostatic diseases are influenced by androgens. The exact reason for an altered and uncontrolled response to androgens, whether benign as in benign prostate hyperplasia (BPH) or malignant as in the case of prostate cancer (PC), is not known in detail. Nevertheless, restriction of androgen receptor activation by reduction of available androgens is of great clinical value in both diseases. In BPH the inhibition of the conversion of testosterone into 5α-dihydrotestosterone (DHT) by 5α-reductase (5AR) is highly efficient and used in general practice, while the situation in PC is more complex. Specific inhibition of 5AR does not provide as efficient relief of symptoms as general androgen deprivation therapy (ADT), and the use of 5ARI for PC prevention is still under debate. Further, the altered steroid metabolism in castration resistant prostate cancer (CRPC) together with the complex paracrine signalling between different androgen responsive cell types, make the development of more specific drugs targeting androgen receptor signalling both more relevant and challenging.