Health Risks Associated with Long-Term Finasteride and Dutasteride Use: It's Time to Sound the Alarm - PMC

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World J Mens Health<br>. 2020 Mar 20;38(3):323–337. doi: 10.5534/wjmh.200012

Health Risks Associated with Long-Term Finasteride and Dutasteride Use: It's Time to Sound the Alarm

Abdulmaged M Traish<br>Abdulmaged M Traish

1Department of Urology, Boston University School of Medicine, Boston, MA, USA.

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1Department of Urology, Boston University School of Medicine, Boston, MA, USA.

✉Correspondence to: Abdulmaged M. Traish. Department of Urology, Boston University School of Medicine, Building A Room 502, 72 East Newton Street, Boston, MA 02118, USA. Tel: +1-617-358-7561, atraish@bu.edu

✉Corresponding author.

Received 2020 Jan 14; Revised 2020 Jan 29; Accepted 2020 Jan 30; Issue date 2020 Jul.

Copyright © 2020 Korean Society for Sexual Medicine and Andrology

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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PMCID: PMC7308241  PMID: 32202088

See letter "Bone Health Risks Associated with Finasteride and Dutasteride Long-Term Use" in volume 39 on page 389.

Abstract

5α-dihydrotestosterone (5α-DHT) is the most potent natural androgen. 5α-DHT elicits a multitude of physiological actions, in a host of tissues, including prostate, seminal vesicles, hair follicles, skin, kidney, and lacrimal and meibomian glands. However, the physiological role of 5α-DHT in human physiology, remains questionable and, at best, poorly appreciated. Recent emerging literature supports a role for 5α-DHT in the physiological function of liver, pancreatic β-cell function and survival, ocular function and prevention of dry eye disease and kidney physiological function. Thus, inhibition of 5α-reductases with finasteride or dutasteride to reduce 5α-DHT biosynthesis in the course of treatment of benign prostatic hyperplasia (BPH) or male pattern hair loss, known as androgenetic alopecia (AGA) my induces a novel form of tissue specific androgen deficiency and contributes to a host of pathophysiological conditions, that are yet to be fully recognized. Here, we advance the concept that blockade of 5α-reductases by finasteride or dutasteride in a mechanism-based, irreversible, inhabitation of 5α-DHT biosynthesis results in a novel state of androgen deficiency, independent of circulating testosterone levels. Finasteride and dutasteride are frequently prescribed for long-term treatment of lower urinary tract symptoms in men with BPH and in men with AGA. This treatment may result in development of non-alcoholic fatty liver diseases (NAFLD), insulin resistance (IR), type 2 diabetes (T2DM), dry eye disease, potential kidney dysfunction, among other metabolic dysfunctions. We suggest that long-term use of finasteride and dutasteride may be associated with health risks including NAFLD, IR, T2DM, dry eye disease and potential kidney disease.

Keywords: Diabetes mellitus, Dry eye syndromes, Hypogonadism, Kidney diseases, Non-alcoholic fatty liver disease, 5-alpha reductase inhibitors

INTRODUCTION

5α-reductases (5α-Rs), a family of several isozymes, play an important role in human physiology by regulating cellular metabolism of androgens, glucocorticoids and other steroids. 5α-Rs are the rate limiting step in the biosynthesis of neuroactive steroids which are critical for central nervous system function [1,2]. 5α-Rs isozymes are widely expressed in many tissues and organs [3]. Metabolites produced by 5α-Rs enzymatic catalysis modulate physiological functions in peripheral and central nervous tissues [1,2,3,4,5,6,7]. Finasteride and dutasteride are synthetic 5α-Rs mechanism-based inhibitors (5α-RIs), also known as suicide substrates [8]. These synthetic drugs are widely prescribed to treat men with benign prostatic hyperplasia (BPH) and young men with pattern hair loss, also known as androgenetic alopecia (AGA) [7]. Although these drugs were purported to be “tolerable and safe”, their potential for causing...