Liver injury associated with the use of selective androgen receptor modulators and post-cycle therapy: Two case reports and literature review

Abstract

BACKGROUND Muscle growth promoters are being developed for the treatment of disease-induced loss of muscle mass. Ligandrol and ostarine are selective androgen receptor modulators (SARMs) with a non-steroidal structure and a presumably more favorable side effect profile. In recent years, these substances with or without “post-cycle therapy” (PCT) are often misused by amateur athletes aiming to promote muscle growth. At the same time, reports on their toxic effects on organ systems are emerging. CASE SUMMARY We report two cases of liver injury in young men who used ligandrol and/or ostarine for a few weeks followed by the use of substances for PCT. Acute liver injury occurred in both cases after stopping SARMs while on PCT. The clinical picture was dominated by jaundice and fatigue. The biochemical pattern showed a mixed type of injury with normal alkaline phosphatase and high concentrations of bilirubin and serum bile acids. Histological evidence showed predominantly cholestatic injury with canalicular bile plugs, ductopenia, and mild hepatocellular damage without significant fibrosis. The patients recovered from the condition after 3 mo. The off target effects of SARMs were likely idiosyncratic, but our report highlights the yet unrecognized effects of other toxic substances used for PCT, supra-therapeutic doses, and the complete absence of monitoring for adverse effects. CONCLUSION Among muscle-building amateur athletes, SARMs (ligandrol or ostarine) and/or substances in PCT may cause cholestatic liver injury with prolonged recovery.

Selective Androgen Receptor Modulator Induced Hepatotoxicity

“…There are numerous anabolic substances and muscle growth promoters that have been developed for the management of muscles, bones, and disorders causing functional decline [1]. The anabolic substances include anabolic androgenic steroids (AASs) such as testosterone, growth hormone, and selective androgen receptor modulators (SARMs) [1].…”

“…There are numerous anabolic substances and muscle growth promoters that have been developed for the management of muscles, bones, and disorders causing functional decline [1]. The anabolic substances include anabolic androgenic steroids (AASs) such as testosterone, growth hormone, and selective androgen receptor modulators (SARMs) [1]. These substances act on androgen receptor (AR), which are part of a superfamily of steroid receptors and have important effects on bone density, muscle mass, coagulation, strength, cognition, and male sexual development.…”

Selective Androgen Receptor Modulator Microparticle Formulation Reverses Muscle Hyperalgesia in Mouse Model of Widespread Muscle Pain

“…Since SARMs have anabolic effects that increase muscle growth and enhance athletic performance, they have become a drug of interest for athletes and weightlifters. In these case reports, the dose of SARM used was either unreported or 10-100 times higher than that used in clinical trials (41)(42)(43). Thus, SARMs should still be viewed as safe when taken at appropriate doses.…”

“…Differences could be related to the microparticle formulation's ability to maintain stable levels, a shorter duration of treatment, or species differences between the mice and humans. There are also published case reports of liver injury due to SARM misuse in young, healthy individuals (41)(42)(43). Since SARMs have anabolic effects that increase muscle growth and enhance athletic performance, they have become a drug of interest for athletes and weightlifters.…”

“…4C). Since SARMs are also being used as a performance enhancing drug by athletes (41)(42)(43), we decided to test if regular SARM administration could be addictive. To do so, we tested if SARM produced rewarding-like behaviors using conditioned place preference testing.…”