Adverse effects of 5α-reductase inhibitors: What do we know, don’t know, and need to know?

Adverse effects of 5α-reductase inhibitors: What do we know, don’t know, and need to know? Steroids are important physiological orchestrators of endocrine as well as peripheral and central nervous system functions. One of the key processes for regulation of these molecules lies in their enzymatic processing by a family of 5α-reductase (5α-Rs) isozymes. By catalyzing a key rate-limiting step in steroidogenesis, this family of enzymes exerts a crucial role not only in the physiological control but also in pathological events. Indeed, both 5α-R inhibition and supplementation of 5α-reduced metabolites are currently used or have been proposed as therapeutic strategies for a wide array of pathological conditions. In particular, the potent 5α-R inhibitors finasteride and dutasteride are used in the treatments of benign prostatic hyperplasia (BPH), as well as in male pattern hair loss (MPHL) known as androgenetic alopecia (AGA). Recent preclinical and clinical findings indicate that 5α-R inhibitors evoke not only beneficial, but also adverse effects. Future studies should investigate the biochemical and physiological mechanisms that underlie the persistence of the adverse sexual side effects to determine why a subset of patients is afflicted with such persistence or irreversible adverse effects. Also a better focus of clinical research is urgently needed to better define those subjects who are likely to be adversely affected by such agents. Furthermore, research on the non-sexual adverse effects such as diabetes, psychosis, depression, and cognitive function are needed to better understand the broad spectrum of the effects these drugs may elicit during their use in treatment of AGA or BPH. In this review, we will summarize the state of art on this topic, overview the key unresolved questions that have emerged on the pharmacological targeting of these enzymes and their products, and highlight the need for further studies to ascertain the severity and duration of the adverse effects of 5α-R inhibitors, as well as their biological underpinnings. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Reviews in Endocrine and Metabolic Disorders Springer Journals

Adverse effects of 5α-reductase inhibitors: What do we know, don’t know, and need to know?

Loading next page...
 
/lp/springer-journals/adverse-effects-of-5-reductase-inhibitors-what-do-we-know-don-t-know-olzgow0FyV
Publisher
Springer Journals
Copyright
Copyright © 2015 by Springer Science+Business Media New York
Subject
Medicine & Public Health; Endocrinology; Diabetes; Internal Medicine
ISSN
1389-9155
eISSN
1573-2606
D.O.I.
10.1007/s11154-015-9319-y
Publisher site
See Article on Publisher Site

Abstract

Steroids are important physiological orchestrators of endocrine as well as peripheral and central nervous system functions. One of the key processes for regulation of these molecules lies in their enzymatic processing by a family of 5α-reductase (5α-Rs) isozymes. By catalyzing a key rate-limiting step in steroidogenesis, this family of enzymes exerts a crucial role not only in the physiological control but also in pathological events. Indeed, both 5α-R inhibition and supplementation of 5α-reduced metabolites are currently used or have been proposed as therapeutic strategies for a wide array of pathological conditions. In particular, the potent 5α-R inhibitors finasteride and dutasteride are used in the treatments of benign prostatic hyperplasia (BPH), as well as in male pattern hair loss (MPHL) known as androgenetic alopecia (AGA). Recent preclinical and clinical findings indicate that 5α-R inhibitors evoke not only beneficial, but also adverse effects. Future studies should investigate the biochemical and physiological mechanisms that underlie the persistence of the adverse sexual side effects to determine why a subset of patients is afflicted with such persistence or irreversible adverse effects. Also a better focus of clinical research is urgently needed to better define those subjects who are likely to be adversely affected by such agents. Furthermore, research on the non-sexual adverse effects such as diabetes, psychosis, depression, and cognitive function are needed to better understand the broad spectrum of the effects these drugs may elicit during their use in treatment of AGA or BPH. In this review, we will summarize the state of art on this topic, overview the key unresolved questions that have emerged on the pharmacological targeting of these enzymes and their products, and highlight the need for further studies to ascertain the severity and duration of the adverse effects of 5α-R inhibitors, as well as their biological underpinnings.

Journal

Reviews in Endocrine and Metabolic DisordersSpringer Journals

Published: Aug 23, 2015

References

  • Life with too much polyprenol: polyprenol reductase deficiency
    Gründahl, JE; Guan, Z; Rust, S; Reunert, J; Müller, B; Chesne, I
  • Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13
    Çalışkan, M; Chong, JX; Uricchio, L; Anderson, R; Chen, P; Sougnez, C
  • Neurosteroids, neuroactive steroids, and symptoms of affective disorders
    Dubrovsky, B
  • Androgen metabolism in adipose tissue: recent advances
    Blouin, K; Veilleux, A; Luu-The, V; Tchernof, A
  • Glucocorticoid receptor variants: clinical implications
    DeRijk, R; Schaaf, M; Kloet, E
  • Neuroactive steroids: state of the art and new perspectives
    Melcangi, RC; Garcia-Segura, LM; Mensah-Nyagan, AG
  • Allopregnanolone: state of the art
    Melcangi, RC; Panzica, GC
  • Neuroactive steroids and the nervous system: further observations on an incomplete tricky puzzle
    Melcangi, RC; Panzica, GC
  • Milestones on Steroids and the Nervous System: 10 years of basic and translational research
    Panzica, GC; Balthazart, J; Frye, CA; Garcia-Segura, LM; Herbison, AE; Mensah-Nyagan, AG
  • Brain androgen and progesterone metabolizing enzymes: biosynthesis, distribution and function
    Lephart, ED; Lund, TD; Horvath, TL
  • Aromatase: a neuroprotective enzyme
    Garcia-Segura, LM; Veiga, S; Sierra, A; Melcangi, RC; Azcoitia, I
  • Hypoglycosylation due to dolichol metabolism defects
    Denecke, J; Kranz, C

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off