5-alpha Reductase and Prostate Cancer
METHODS We searched Pubmed for data obtained from pharmacological, preclinical and clinical studies.
RESULTS 5AR1 expression increases with increasing aggressiveness and extension of malignant prostatic disease. Conversely, 5AR2 expression decreases from benign prostatic tissue to localized prostate cancer. The efficacy of 5AR2 monotherapy with finasteride alone or in combination with an androgen receptor antagonist on more final outcome measures seems to be limited. Combining an androgen receptor antagonist with a 5AR inhibitor in patients with asymptomatic, locally advanced or recurrent prostate cancer might be a reasonable first therapeutic hormonal approach. As plasma testosterone levels are maintained, beneficial effects on quality of life, potency and sexual function are expected. From studies on the dual 5AR inhibitor dutasteride, the drug produces a biochemical response in some men who progressed under androgen-deprivation therapy, and is generally well tolerated.
CONCLUSIONS Achieving more potent suppression of intracellular DHT synthesis by 5AR inhibition is expected to provide clinical benefit to patients. Previous studies have shown that 5AR inhibition, by dutasteride in particular, halts/delays the progression of disease, and might even cause regression of disease in patients with advanced prostate cancer.
Vis AN, Schröder FH.
Key targets of hormonal treatment of prostate cancer. Part 2: the androgen receptor and 5alpha-reductase.
Department of Urology, VU Medical Centre, Amsterdam, and Department of Urology, Erasmus Medical Centre, Rotterdam, the Netherlands.