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        The Dark Side of 5α-Reductase Inhibitors’ Therapy: Sexual Dysfunction, High Gleason Grade Prostate Cancer and Depression

        Abdulmaged M. Traish,Ashwini Mulgaonkar,Nicholas Giordano 대한비뇨의학회 2014 Investigative and Clinical Urology Vol.55 No.6

        With aging, abnormal benign growth of the prostate results in benign prostate hyperplasia(BPH) with concomitant lower urinary tract symptoms (LUTS). Because theprostate is an androgen target tissue, and transforms testosterone into 5α-dihydrotestosterone(5α-DHT), a potent androgen, via 5α-reductase (5α-R) activity, inhibitingthis key metabolic reaction was identified as a target for drug development to treatsymptoms of BPH. Two drugs, namely finasteride and dutasteride were developed asspecific 5α-reductase inhibitors (5α-RIs) and were approved by the U.S. Food and DrugAdministration for the treatment of BPH symptoms. These agents have proven usefulin the reducing urinary retention and minimizing surgical intervention in patients withBPH symptoms and considerable literature exists describing the benefits of theseagents. In this review we highlight the adverse side effects of 5α-RIs on sexual function,high grade prostate cancer incidence, central nervous system function and ondepression. 5α-Rs isoforms (types 1–3) are widely distributed in many tissues includingthe central nervous system and inhibition of these enzymes results in blockade of synthesisof several key hormones and neuro-active steroids leading to a host of adverseeffects, including loss of or reduced libido, erectile dysfunction, orgasmic dysfunction,increased high Gleason grade prostate cancer, observed heart failure and cardiovascularevents in clinical trials, and depression. Considerable evidence exists frompreclinical and clinical studies, which point to significant and serious adverse effectsof 5α-RIs, finasteride and dutasteride, on sexual health, vascular health, psychologicalhealth and the overall quality of life. Physicians need to be aware of such potential adverseeffects and communicate such information to their patients prior to commencing5α-RIs therapy.

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