Abstract and Introduction
Abstract
5-alpha reductase inhibitors (5-ARIs) are commonly used and widely available, with benefits observed from their effect on androgen signalling. Their effect relies on the inhibition of the 5-alpha reductase enzyme which aids in the conversion of testosterone to dihydrotestosterone. 5-ARIs have increasing clinical relevance outside of benign prostatic hyperplasia (BPH). Such development requires clinicians to have an updated review to guide clinical practices. This review details the pharmacology and mechanisms of action for 5-ARIs and how this relates to multiple clinical indications. Of note, is the debunked association between finasteride and increased risk of high-grade prostate cancer. Furthermore, adverse effects of 5-ARI use are detailed in this review, with specific mentions to post-finasteride syndrome. In addition to overviews pertaining to BPH and prostate cancer, much attention has also been focused on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The androgen axis may be associated with an increased virulence for SARS-CoV-2 in men, with some reporting a correlation between the severity of illness and androgenic alopecia. Since these observations, the role of antiandrogens, including 5-ARIs, has been explored further in SARS-CoV-2. Increasing understanding of pathological processes involving the androgen axis in which 5-ARIs work, has led to increasing clinical indications for 5-ARIs. Several novel off-label indications have been suggested including its potential role in the pathogenesis of SARS-CoV-2, but to date, these claims have not been substantiated. Previously held truths regarding the role of 5-ARIs and prostate carcinogenesis have been contested, inadvertently leading to the re-exploration of 5-ARIs utility in prostate cancer. With growing evidence into pathological processes involving the androgen axis, 5-ARIs are likely to become increasingly more used. This review serves as a timely update of 5 ARIs pharmacology, current indications and potential future directions.
Introduction
5-alpha reductase inhibitors (5-ARIs) are commonly used and widely available, with benefits observed from their effect on androgen signalling. Initially licenced for use in benign prostatic hyperplasia (BPH), finasteride and dutasteride are the two major 5-ARIs that are commercially available and in use today.[1,2] Their effect relies on the inhibition of the 5-alpha reductase (5α-reductase) enzyme which aids in the conversion of testosterone to dihydrotestosterone (DHT).[3]
Since its introduction, the clinical indication for 5-ARIs has grown from BPH to include androgenetic alopecia (AGA) and hirsutism.[1] As more pathological processes are identified as being mediated by DHT, the clinical indications and utility of 5-ARIs expand. The relationship between 5-ARIs and prostate cancer is of particular interest due to the androgen-driven nature of prostate carcinogenesis.[3,4] Other new associations have been observed between 5-ARIs and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), including with reduced disease severity and mortality.[5,6]
With new developments and increasing clinical indications, an up-to-date review of 5-ARIs is warranted, helping to inform clinical practice. This narrative review addresses the mechanism of action of 5-ARIs, potential adverse effects, current clinical indications including indications within and outside of urology.
Transl Androl Urol. 2023;12(3):487-496. © 2023 AME Publishing Company
