Poster 390: Systematic Review of SARMs Abuse in Athletes

OBJECTIVES: Selective Androgen Receptor Modulators (SARMs) are small-molecule compounds that exert agonist and antagonist effects on androgen receptors in a tissue-specific fashion. SARMs are not FDA approved in the USA, but are readily available for purchase online. Increasingly, athletes have turned to SARMs in recent years as a means of augmenting lean muscle mass, evidenced by positive tests across multiple athletic organizations including the NFL, NBA, UFC, NCAA, and Olympics. The safety of SARMs for anabolic effects has not been established, and case reports associate SARMs with deleterious effects, including drug-induced liver injury (DILI), myocarditis, and tendon rupture. The purpose of this novel systematic review is to provide a comprehensive synthesis of the SARMs literature, in order to help sports medicine clinicians understand the clinical effects, treatment protocols, banned substance implications, and potential contamination of athlete-consumed SARMs. METHODS: A systematic review of the English-language literature from PubMed, Cochrane, and Embase was performed according to PRISMA guidelines. Articles relevant to SARMs clinical outcomes, case reports, safety profiles, and doping control were included. Reviews, meta-analyses, editorials, and conference abstracts were excluded. Ostarine (Enobosarm, GTx-027, MK-2886, S-22), Ligandrol (LGD- 4033, VK5211), RAD-140 (Testolone), and Andarine (S-4, GTx-007) were the primary focus, given the reported widespread recreational abuse of these specific SARMs. RESULTS: The literature search yielded 1382 abstracts, and a total of 23 articles from 2011 to 2022 were identified for inclusion. Three of the five clinical trials reported significant increases in lean body mass (LBM) (Table 1). Five studies reported on drug testing screening methods designed for human-use (Table 2). A liquid chromatography with tandem mass spectrometry urine screening method demonstrated the lowest limit of detection for detecting all four SARMs. Five studies analyzed purchased SARMs for contamination (Table 3). Forty-nine samples of Ostarine, Ligandrol, RAD-140, and Andarine were assessed: 26 out of 49 samples (55%) varied substantially from the label by dosing, purity, or type of compound. Eight case reports described 10 cases of recreational SARMs use and treatment, with all articles published in the last 2 years (Table 4). All included patients were male, half were athletes, and all ingested SARMs orally for an average course of 6 weeks. The specific SARM compounds consumed were Ostarine (4/10), Ligandrol (4/10), and RAD-140 (2/10). Several patients presented with jaundice (5/10), pruritus (4/10), and icteric sclera (4/10). 8 of these patients were diagnosed with DILI, 1 was diagnosed with acute myocarditis, and 1 sustained bilateral Achilles tendon ruptures following two courses of SARMs. CONCLUSIONS: Athletes most commonly purchase SARMs online, and a majority of these compounds are contaminated with other substances. Ostarine, Ligandrol, and RAD-140 appear to be the most frequently abused SARM compounds. SARM screening modalities include urine, hair, and nail detection. Although SARMs may increase LBM at low doses, case reports suggest SARMs users consume SARMs at much higher doses than studied, which may increase the risk of harmful side effects such as liver injury, cardiovascular events, and tendon damage (perhaps akin to anabolic androgenic steroids). Further basic science and clinical studies are warranted to validate these early reported findings regarding SARMs.