Selective androgen receptor modulator use and related adverse events including drug-induced liver injury: Analysis of suspected cases

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Abstract

Purpose

Selective androgen receptor modulators (SARMs) have demonstrated agonist activity on the androgen receptor in various tissues, stimulating muscle mass growth and improving bone reconstruction. Despite being in clinical trials, none has been approved by the Food and Drug Administration (FDA) or European Medicines Agency for pharmacotherapy. Still, SARMs are very popular as performance-enhancing drugs. The FDA has issued warnings about the health risks associated with SARMs, but the long-term exposure and possible adverse events still need to be fully understood. This review aims to evaluate the adverse events associated with using SARMs by humans.

Methods

PubMed database was searched from September 16, 2022, to October 2, 2023. In total, 20 records were included in the final review. Data from preclinical and clinical studies supported the review.

Results

Since 2020, 20 reports of adverse events, most described as drug-induced liver injury associated with the use of SARM agonists, have been published. The main symptoms mentioned were cholestatic or hepatocellular liver injury and jaundice. Limited data are related to the dosages and purity of SARM supplements.

Conclusion

Promoting SARMs as an anabolic agent in combination with other performance-enhancing drugs poses a risk to users not only due to doping controls but also to health safety. The lack of quality control of consumed supplements makes it very difficult to assess the direct impact of SARMs on the liver and their potential hepatotoxic effects. Therefore, more detailed analyses are needed to determine the safety of using SARMs.

Related collections

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Malondialdehyde (MDA), 4-hydroxy-nonenal (HNE) and the F2-isoprostane 15(S)-8-iso-prostaglandin F2α (15(S)-8-iso-PGF2α) are the best investigated products of lipid peroxidation. MDA, HNE and 15(S)-8-iso-PGF2α are produced from polyunsaturated fatty acids (PUFAs) both by chemical reactions and by reactions catalyzed by enzymes. 15(S)-8-iso-PGF2α and other F2-isoprostanes are derived exclusively from arachidonic acid (AA). The number of PUFAs that may contribute to MDA and HNE is much higher. MDA is the prototype of the so called thiobarbituric acid reactive substances (TBARS). MDA, HNE and 15(S)-8-iso-PGF2α are the most frequently measured biomarkers of oxidative stress, namely of lipid peroxidation. In many diseases, higher concentrations of MDA, HNE and 15(S)-8-iso-PGF2α are measured in biological samples as compared to health. Therefore, elevated oxidative stress is generally regarded as a pathological condition. Decreasing the concentration of biomarkers of oxidative stress by changing life style, by nutritional intake of antioxidants or by means of drugs is generally believed to be beneficial to health. Reliable assessment of oxidative stress by measuring MDA, HNE and 15(S)-8-iso-PGF2α in biological fluids is highly challenging for two important reasons: Because of the duality of oxidative stress, i.e., its origin from chemical and enzymatic reactions, and because of pre-analytical and analytical issues. This article focuses on these key issues. It reviews reported analytical methods and their principles for the quantitative measurement of MDA, HNE and 15(S)-8-iso-PGF2α in biological samples including plasma and urine, and critically discusses their biological and biomedical outcome which is rarely crystal clear and free of artefacts.

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Author and article information

Contributors

Karol Jędrejko: karol.jedrejko@gmail.com

Journal

Journal ID (nlm-ta): Eur J Clin Pharmacol

Journal ID (iso-abbrev): Eur J Clin Pharmacol

Title: European Journal of Clinical Pharmacology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0031-6970

ISSN (Electronic): 1432-1041

Publication date (Electronic): 7 December 2023

Publication date PMC-release: 7 December 2023

Publication date (Print): 2024

Volume: 80

Issue: 2

Pages: 185-202

Affiliations

[1 ]Department of Animal Physiology, Biochemistry and Biostructure, Poznań University of Life Sciences, ( https://ror.org/03tth1e03) 60-637 Poznan, Poland

[2 ]Department of Pharmaceutical Botany, Faculty of Pharmacy, Jagiellonian University Medical College, ( https://ror.org/03bqmcz70) Medyczna 9 Street, 30-688 Kraków, Poland

[3 ]Human Performance Laboratory, School of Physical Education, Autonomous University of Nuevo Leon, ( https://ror.org/01fh86n78) San Nicolas de los Garza, Mexico

[4 ]Department of Research and Graduate Studies in Food Sciences, School of Chemistry, Autonomous University of Queretaro, ( https://ror.org/00v8fdc16) Santiago de Queretaro, Mexico

[5 ]Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, ( https://ror.org/04p2y4s44) Warsaw, Poland

Article

Publisher ID: 3592

DOI: 10.1007/s00228-023-03592-3

PMC ID: 10847181

PubMed ID: 38059982

SO-VID: 18112667-a9f5-4815-85ee-5d29930a8ef3

License:

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