Selective Androgen Receptor Modulators (SARMs) Effects on Physical Performance: A Systematic Review of Randomized Control Trials.

OBJECTIVE: Selective androgen receptor modulators (SARMs) are potential treatments for ameliorating age-related physical dysfunctions caused by sarcopenia, cachexia and chronic illnesses such as cancer. The purpose of this systematic review is to analyse the effect of SARMs on physical performance and body and evaluate their safety profile. METHODS: A systematic review search criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed in three databases for studies reporting physical parameter outcomes after SARM intervention. Study variables included title, author, publication date, study year, number of patients, dosage, mean age, mean follow-up time, pre and post-intervention outcomes and rates of complications. RESULTS: Nine studies, including 970 patients with a mean age of 57.1 years (35.3-75.9) and a mean follow-up of 80 days (14-180), were included. Six SARMs were analysed: LGD-4033, PF-06260414, GSK2881078, GTx-024, MK-0773 and OPK-88004. Mean pre-intervention stair climbing power (five studies), one repetition maximum leg press (four studies) and short physical performance battery (SPPB) score (two studies), lean body mass (seven studies) and fat mass (five studies) were 352.24 W (69.79-678.7), 1822.77 N (1176.8-2407.3), 9.15 (7.95-9.9), 49.46 kg (30.94-63.9) and 21.99 kg (13.3-33), respectively. Mean post-intervention values were 315.16 W (89.46-525.73 W), 2191.27 N (1375.87-2462.9 N), 9.79 (8.88-10.4), 50.86 kg (31.02-67.29) and 21.85 kg (12.54-32.16), respectively. CONCLUSION: SARMs have a positive effect on physical performance and body composition and are associated with moderate rates of mild to moderate adverse effects (AEs) and a low rate of severe AEs.

Selective Androgen Receptor Modulators Leading to Liver Injury: A Case Report.

Selective androgen receptor modulators (SARMs) have gained popularity for their alleged ability to selectively target androgen receptors, potentially offering muscle-building benefits with fewer side effects than traditional steroids. However, the safety profile of SARMs, including RAD-140, is not fully understood. This case report presents a 29-year-old male who developed liver injury after taking RAD-140. The patient experienced jaundice and elevated liver enzymes after three months of RAD-140 use. A liver ultrasound revealed hepatic steatosis and a hyperechoic lesion. Symptoms resolved after discontinuing RAD-140. Similar cases of liver injury associated with RAD-140 have been reported, highlighting the potential hepatotoxicity of this SARM. Discontinuation of RAD-140 appears to reverse liver injury, but the long-term effects and risks of SARM use remain unclear. This case highlights the need for caution and monitoring when considering SARMs for performance enhancement.

Detection of the selective androgen receptor modulator S-23 and its metabolites in equine urine and plasma following oral administration.

S-23 is an arylpropionamide selective androgen receptor modulator that has been investigated in animal models for use as a male hormonal contraceptive but is not yet available therapeutically. S-23 is available alongside other selective androgen receptor modulators (SARMs) to purchase online via uncontrolled sites, sold as supplement products. It has been detected in several human doping cases, highlighting the importance of identifying the best analytical targets for equine doping control. The purpose of this study was to investigate the detection of S-23 and its phase I metabolites in equine urine and plasma following a multiple dose oral administration to two Thoroughbred racehorses. Liquid chromatography-high resolution mass spectrometry was used for metabolite identification, and liquid chromatography-tandem mass spectrometry was used for full sample analysis and generation of urine and plasma profiles. S-23 and seven phase I metabolites were observed in urine following enzyme hydrolysis and solvolysis. The most abundant analyte detected was the hydroxylated 4-amino-2-(trifluoromethyl)benzonitrile metabolite, which also allowed the longest duration of detection in urine from both horses, for up to 360 h following administration. The data suggest that this metabolite was likely to be highly conjugated with both sulphate and glucuronide moieties. In plasma, S-23 and two phase I metabolites were observed. S-23 was the most abundant analyte detected for both horses, allowing detection for up to 143 h post-administration. To the best of the authors' knowledge, this is the first report of S-23 and metabolites in equine urine and plasma samples.

Ambient ionization mass spectrometry provides screening of selective androgen receptor modulators.

Ambient ionization mass spectrometry allows for analysis of samples in their natural state, i.e., with no sample pre-treatment. It can be viewed as a fast, simple, and economical analysis, but its main disadvantages include a lower analytical performance due to the presence of complex sample matrix and the lack of chromatographic separation prior to the introduction of the sample into the mass spectrometer. Here we present an application of two ambient ionization mass spectrometry techniques, i.e., Desorption Atmospheric Pressure Photoionization and Dielectric Barrier Discharge Ionization, for the analysis of known Selective Androgen Receptor Modulators, which represent common compounds of abuse in professional and semiprofessional sport. Eight real samples of illegal food supplements, seized by the local law enforcement, were used to test the performance of the ambient mass spectrometry and the results were validated against a newly developed targeted LC-UV-MS/MS method performed in multiple reaction monitoring mode with an external calibration for each analyte. In order to decide whether or not the compound can be declared as present, we proposed a system of rules for the interpretation of the obtained spectra. The criteria are based on mass spectrum matching (5-10 ppm accuracy from the theoretical exact mass and a correct isotopic pattern), duration of the mass signal (three or five consecutive scans, depending on the instrumentation used), and intensity above the background noise (threefold increase in intensity and absolute intensity above 5E4 or 1E5, depending on the instrumentation). When applying these criteria, good agreement was found between the tested methods. Ambient ionization techniques were effective at detecting SARMs at pharmacologically relevant doses, i.e., approximately above 1 mg per capsule, although they may fail to detect lower levels or isomeric species. It is demonstrated that when adhering to a set of clear and consistent rules, ambient mass spectrometry can be employed as a qualitative technique for the screening of illegal SARMs with sufficient confidence and without the necessity to perform a regular LC-MS analysis.

Advances in SARMs anti-doping analysis.

Selective androgen receptor modulators (SARMs) are performance-enhancing drugs (PEDs) that stimulate anabolism, increase muscle mass and strength and promote recovery from exercise. The use of SARMs in sports is considered doping and is strictly prohibited by the World Anti-Doping Agency (WADA) and the International Federation of Horseracing Authorities (IFHA). To monitor the abuse of SARMs in sports, it is essential to develop advanced, selective and sensitive analytical methods that provide reliable results. This review evaluates the advances in this area, with a focus on the identification of target analytes related to SARMs, such as SARMs, their metabolites or markers. The aim is to identify targets that could extend the detection windows of SARMs, provide scientific support for results management and/or offer an indirect biomarker-based approach to doping control. This review also aims to evaluate the current liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) methods developed for the monitoring of SARMs in different biological matrices, including traditional matrices such as urine and serum/plasma samples, as well as alternative matrices such as dried blood spots, hair and nail samples.

Illegal products containing selective androgen receptor modulators purchased online from Italy: health risks for consumers.

Background: Selective androgen receptor modulators (SARMs) are small synthetic drug molecules that are still not approved as medicine in Europe or the United States but are sold on illegal websites to improve sport performance, particularly bodybuilding. Aim: To address the quality issues of illegal SARM products and their increasing diffusion in Italy with their potential health risks for consumers. Methods: Web-based tools were used to investigate retail websites, trending searches, and information exchange via social media. Thirteen SARM products, purchased on retail websites accessible from Italy, were subject to visual inspection and chemical analysis by mass spectrometry and quantitative nuclear magnetic resonance. Outcomes: The primary outcome was demonstration of additional health risks due to the illicit presence of other active ingredients, contamination, and misdosage in SARM products sold on the internet. The secondary outcome was to show the increasing trend of interest in Italy for these products. Results: Most websites reported misleading information; specifically, the statement "for research only" was reported notwithstanding indications on dosage and training phases. The trending search showed that interest toward SARMs increased in Italy in the last years. The use of these products is clearly encouraged by the emerging phenomenon of "broscience" as revealed in socials. Visual inspection evidenced nonconform labeling. Qualitative analysis confirmed the presence of the stated SARM in about 70% of samples. In 23% of samples, the expected SARM was not detected but a different one instead, and in 1 sample, no SARMs were detected. Other undeclared pharmaceutical substances (tamoxifen, clomifene, testosterone, epimethandienone, tadalafil) were measured in 30% of samples. The copresence of >1 active substance was observed in >60% of samples. Quantitative nuclear magnetic resonance data showed nonuniform content ranging from 30% to 90% of the label claim. Clinical Implications: The use of SARMs, in the presence of unexpected life-threatening reactions in persons using the products to increase sport performance, should be assessed. Strengths and Limitations: This investigation involved an integrated approach to study SARM products and related sociologic aspects. The main shortcomings are the limited number of samples and retail websites in the clear web investigated. Conclusion: SARMs sold online as food supplement-like products represent a health hazard due to the presence of unapproved and undeclared active substances. The presence of contaminants clearly indicates the absence of good manufacturing practices in the production, which increases the health risks.

Ostarine blunts the effect of endurance training on submaximal endurance in rats.

The purpose of this study is to study the effects of ostarine alone and in combination with endurance training in sexually mature, male Wistar rats. The rats were divided into a treadmill-trained group and a sedentary group. Half of each group received either ostarine or vehicle for 8 weeks (n = 10 each, in total n = 40). We examined some functional, hormonal, and anthropometric parameters and the myogenic gene expression of myostatin, insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor-A (VEGF-A) in m. gastrocnemius. Ostarine decreased submaximal endurance and increased myogenic gene expression of myostatin but had no effect on maximal time to exhaustion and grip strength. Training increased submaximal endurance, maximal time to exhaustion, and grip strength. Our results indicate that both exercise and ostarine treatment had no significant effects on serum levels of luteinizing hormone, follicle-stimulating hormone, and testosterone, or on the myogenic gene expression of IGF-1 and VEGF-A. Neither ostarine nor the training had a significant effect on the testis, liver, and heart weights. In conclusion, ostarine had no effect on anthropometric and hormonal parameters but increased the myostatin gene expression in muscle. The SARM treatment decreased submaximal endurance without affecting maximal time to exhaustion, and training increased both metrics.

Advantage of ostarine over raloxifene and their combined treatments for muscle of estrogen-deficient rats.

PURPOSE: Selective androgen (ostarine, OST) and estrogen (raloxifene, RAL) receptor modulators with improved tissue selectivity have been developed as alternatives to hormone replacement therapy. We investigated the combined effects of OST and RAL on muscle tissue in an estrogen-deficient rat model of postmenopausal conditions. METHODS: Three-month-old Sprague Dawley rats were divided into groups: (1) untreated non-ovariectomized rats (Non-OVX), (2) untreated ovariectomized rats (OVX), (3) OVX rats treated with OST, (4) OVX rats treated with RAL, (5) OVX rats treated with OST and RAL. Both compounds were administered in the diet. The average dose received was 0.6 ± 0.1 mg for OST and 11.1 ± 1.2 mg for RAL per kg body weight/day. After thirteen weeks, rat activity, muscle weight, structure, gene expression, and serum markers were analyzed. RESULTS: OST increased muscle weight, capillary ratio, insulin-like growth factor 1 (Igf-1) expression, serum phosphorus, uterine weight. RAL decreased muscle weight, capillary ratio, food intake, serum calcium and increased Igf-1 and Myostatin expression, serum follicle stimulating hormone (FSH). OST + RAL increased muscle nucleus ratio, uterine weight, serum phosphorus, FSH and luteinizing hormone and decreased body and muscle weight, serum calcium. Neither treatment changed muscle fiber size. OVX increased body and muscle weight, decreased uterine weight, serum calcium and magnesium. CONCLUSION: OST had beneficial effects on muscle in OVX rats. Side effects of OST on the uterus and serum electrolytes should be considered before using it for therapeutic purposes. RAL and RAL + OST had less effect on muscle and showed endocrinological side effects on pituitary-gonadal axis.

Variation of Sequential Ligandrol (LGD-4033) Metabolite Levels in Routine Anti-Doping Urine Samples Detected with or without Other Xenobiotics.

Ligandrol, also known as LGD-4033, belongs to the group of selective androgen receptor modulators (SARMs). Ligandrol was first included in the WADA Prohibited List in 2018. This work presents a method that allows for the detection and identification of ligandrol and its metabolite in athletes' urine and in dietary supplements by means of ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Samples were prepared according to an approach involving acid hydrolysis and double liquid-liquid extraction (LLE). Furthermore, due to the lack of reference material for ligandrol metabolites, the urine collected from the control excretion study was analyzed. The presented method is appropriate to monitor ligandrol and its metabolites. The samples collected for doping control purpose contained multiple metabolites, which may potentially rule out the hypothesis of ingesting a single 1 µg or 10 µg dose only. Another aspect to take into account is that ligandrol can be applied together with SARMs, steroids, and GHSs. This will also affect the substances' metabolism and elimination. It is also worth noting that dietary supplements may contain ligandrol as an official ingredient or as a contaminant. The described method may be usefully applied by other anti-doping or toxicological laboratories.

Androgen Receptor and Cardiovascular Disease: A Potential Risk for the Abuse of Supplements Containing Selective Androgen Receptor Modulators.

The androgen receptor (AR) is a member of the family of ligand-activated transcription factors. Selective androgen receptor modulators (SARMs) exert their biological function through complex interactions with the AR. It has been speculated that overexertion of AR signaling cascades as a result of SARM abuse can be a risk factor for the development of various cardiovascular diseases. The present literature review explores the implications of the interaction between SARMs and the AR on cardiovascular health by focusing on the AR structure, function, and mechanisms of action, as well as the current clinical literature on various SARMs. It is shown that SARMs may increase the risk of cardiovascular diseases through implications on the renin-angiotensin system, smooth muscle cells, sympathetic nervous system, lipid profile, inflammation, platelet activity, and various other factors. More research on this topic is necessary as SARM abuse is becoming increasingly common. There is a noticeable lack of clinical trials and literature on the relationship between SARMs, cardiovascular diseases, and the AR. Future in vivo and in vitro studies within this field are vital to understand the mechanisms that underpin these complex interactions and risk factors.

Advances in Endocrine Therapy for Hormone Receptor-Positive Advanced Breast Cancer.

PURPOSE OF REVIEW: To provide an overview of the current management of hormone receptor-positive (HR +) advanced breast cancer as well as highlight ongoing clinical investigation and novel therapies in development. RECENT FINDINGS: CDK4/6 inhibition plus endocrine therapy is standard front-line therapy for HR + advanced breast cancer. Continuation of CDK4/6 inhibitors in combination with alternative endocrine therapy has been evaluated in the second-line setting. Alternatively, endocrine therapy in combination with PI3K/AKT pathway targeting agents has been studied, particularly in patients with PI3K pathway alterations. The oral SERD elacestrant has also been evaluated in patients with ESR1 mutation. Many novel endocrine agents and targeted agents are in development. An improved understanding of combination therapies and sequencing of therapies is needed to optimize the treatment paradigm. Biomarker development is needed to guide treatment decisions. Advances in the treatment of HR + breast cancer have resulted in improved patient outcomes in recent years. Continued development efforts with identification of biomarkers to better understand response and resistance to therapy are needed.

Investigation of in vitro generated metabolites of GLPG0492 using equine liver microsomes for doping control.

An effective alternative to testosterone therapy is selective androgen receptor modulators, a class of compounds that has a tissue-specific effect on muscle and bone. These drugs, which enhance performance, pose a severe abuse risk in competitive sports. GLPG0492 is one of the selective androgen receptor modulators discovered in recent decades. This compound has a unique tissue-specific action for muscle and bone against steroid receptors and acts as a partial agonist for androgen receptors. This study examined GLPG0492 and its metabolites in vitro using equine liver microsomes. Liquid chromatography-high-resolution mass spectrometry was utilized to determine the probable structures of detected metabolites. This study identified 39 metabolites of GLPG0492 (21 phase I and 18 phase II). The hydroxylation of GLPG0492 results in monohydroxylated and dihydroxylated metabolites. Additionally, the study detected dissociated side chains (3-methyl and 4-(hydroxymethyl)) and corresponding hydroxylated metabolites. A series of glucuronic acid- and sulfonic acid-conjugated analogs of GLPG0492 were detected during phase II of the study. The findings might help in the detection of GLPG0492 and the elucidation of its illegal use in equestrian sports.

Understanding and managing the suppression of spermatogenesis caused by testosterone replacement therapy (TRT) and anabolic-androgenic steroids (AAS).

Use of testosterone replacement therapy (TRT) and anabolic-androgenic steroids (AAS) has increased over the last 20 years, coinciding with an increase in men presenting with infertility and hypogonadism. Both agents have a detrimental effect on spermatogenesis and pose a clinical challenge in the setting of hypogonadism and infertility. Adding to this challenge is the paucity of data describing recovery of spermatogenesis on stopping such agents. The unwanted systemic side effects of these agents have driven the development of novel agents such as selective androgen receptor modulators (SARMs). Data showing natural recovery of spermatogenesis following cessation of TRT are limited to observational studies. Largely, these have shown spontaneous recovery of spermatogenesis after cessation. Contemporary literature suggests the time frame for this recovery is highly variable and dependent on several factors including baseline testicular function, duration of drug use and age at cessation. In some men, drug cessation alone may not achieve spontaneous recovery, necessitating hormonal stimulation with selective oestrogen receptor modulators (SERMs)/gonadotropin therapy or even the need for assisted reproductive techniques. However, there are limited prospective randomized data on the role of hormonal stimulation in this clinical setting. The use of hormonal stimulation with agents such as gonadotropins, SERMs, aromatase inhibitors and assisted reproductive techniques should form part of the counselling process in this cohort of hypogonadal infertile men. Moreover, counselling men regarding the detrimental effects of TRT/AAS on fertility is very important, as is the need for robust randomized studies assessing the long-term effects of novel agents such as SARMs and the true efficacy of gonadotropins in promoting recovery of spermatogenesis.

Human In Vivo Metabolism and Elimination Behavior of Micro-Dosed Selective Androgen Receptor Modulator RAD140 for Doping Control Purposes.

RAD140 is a selective androgen receptor modulator which has been abused in sporting competitions. Its use is prohibited by the World Anti-Doping Agency (WADA) for athletes at all times. In addition to its illicit use, adverse analytical findings of RAD140 in doping control samples might result from other scenarios, e.g., the ingestion of contaminated dietary supplements. The differentiation between samples resulting from such contamination scenarios and intentional doping presents a considerable challenge, as little is known about the metabolism and elimination behavior of RAD140 in humans. In this study, six micro-dose excretion studies with five adult male volunteers each were conducted, and urine samples were analyzed by means of LC-HRMS/MS. Multiple metabolites, firstly detected in human urine, are described in this study. The sample preparation included an enzymatic hydrolysis step, which facilitated the estimation of RAD140 concentrations in urine. The elimination profiles and detection times for six metabolites as well as the intact drug are presented. The method was extensively characterized and deemed fit-for-purpose. The metabolite ratios were investigated for their predictive power in estimating the dose of RAD140 intake. The presented data will aid in better case result management in future doping cases involving RAD140.

Combination of selective androgen and estrogen receptor modulators in orchiectomized rats.

PURPOSE: Selective androgen and estrogen receptor modulators, ostarine (OST) and raloxifen (RAL), reportedly improve muscle tissue and offer therapeutic approaches to muscle maintenance in the elderly. The present study evaluated the effects of OST and RAL and their combination on musculoskeletal tissue in orchiectomized rats. METHODS: Eight-month-old Sprague Dawley rats were analyzed. Experiment I: (1) Untreated non-orchiectomized rats (Non-ORX), (2) untreated orchiectomized rats (ORX), (3) ORX rats treated with OST during weeks 0-18 (OST-P), (4) ORX rats treated with OST during weeks 12-18 (OST-T). Experiment II: 1) Non-ORX, (2) ORX, 3) OST-P, (4) ORX rats treated with RAL, during weeks 0-18 (RAL-P), 5) ORX rats treated with OST + RAL, weeks 0-18 (OST + RAL-P). The average daily doses of OST and RAL were 0.4 and 7 mg/kg body weight (BW). Weight, fiber size, and capillarization of muscles, gene expression, serum markers and the lumbar vertebral body were analyzed. RESULTS: OST-P exerted favorable effects on muscle weight, expression of myostatin and insulin growth factor-1, but increased prostate weight. OST-T partially improved muscle parameters, showing less effect on the prostate. RAL-P did not show anabolic effects on muscles but improved body constitution by reducing abdominal area, food intake, and BW. OST + RAL-P had an anabolic impact on muscle, reduced androgenic effect on the prostate, and normalized food intake. OST and RAL improved osteoporotic bone. CONCLUSIONS: The OST + RAL treatment appeared to be a promising option in the treatment of androgen-deficient conditions and showed fewer side effects than the respective single treatments.

Investigations into the elimination profiles and metabolite ratios of micro-dosed selective androgen receptor modulator LGD-4033 for doping control purposes.

LGD-4033 (ligandrol) is a selective androgen receptor modulator (SARM), which is prohibited in sports by the World Anti-Doping Agency (WADA) and led to 62 adverse analytical findings (AAFs) in 2019. But not only deliberate doping with LGD-4033 constitutes a problem. In the past years, some AAFs that concerned SARMs can be attributed to contaminated dietary supplements (DS). Thus, the urgency to develop methods to differentiate between inadvertent doping and abuse of SARMs to benefit from the performance-enhancing effect of the compound in sports is growing. To gain a better understanding of the metabolism and excretion patterns of LGD-4033, human micro-dose excretion studies at 1, 10, and 50 µg LGD-4033 were conducted. Collected urine samples were prepared for analysis using enzymatic hydrolysis followed by solid-phase extraction and analyzed via LC-HRMS/MS. Including isomers, a total of 15 phase I metabolites were detected in the urine samples. The LC-HRMS/MS method was validated for qualitative detection of LGD-4033, allowing for a limit of detection (LOD) of 8 pg/mL. The metabolite M1, representing the epimer of LGD-4033, was synthesized and the structure elucidated by NMR spectroscopy. As the M1/LGD-4033 ratio changes over time, the ratio and the approximate LGD-4033 concentration can contribute to estimating the time point of drug intake and dose of LGD-4033 in doping control urine samples, which is particularly relevant in anti-doping result management.

Identification of equine in vitro metabolites of seven non-steroidal selective androgen receptor modulators for doping control purposes.

Selective androgen receptor modulators, SARMs, are a large class of compounds developed to provide therapeutic anabolic effects with minimal androgenic side effects. A wide range of these compounds are available to purchase online and thus provide the potential for abuse in sports. Knowledge of the metabolism of these compounds is essential to aid their detection in doping control samples. In vitro models allow a quick, cost-effective response where administration studies are yet to be carried out. In this study, the equine phase I metabolism of the non-steroidal SARMs GSK2881078, LGD-2226, LGD-3303, PF-06260414, ACP-105, RAD-140 and S-23 was investigated using equine liver microsomes. Liquid chromatography coupled to a QExactive Orbitrap mass spectrometer allowed identification of metabolites with high resolution and mass accuracy. Three metabolites were identified for both GSK2881078 and LGD-2226, four for LGD-3303 and RAD-140, five for PF-06260414, twelve for ACP-105 and ten for S-23. The equine metabolism of GSK-2881078, LGD-2226, LGD-3303 and PF-06260414 is reported for the first time. Although the equine metabolism of ACP-105, RAD-140 and S-23 has previously been reported, the results obtained in this study have been compared with published data.

The forensic response after an adverse analytical finding (doping) involving a selective androgen receptor modulator (SARM) in human athlete.

Selective androgen receptor modulators (SARMs) are a class of drugs presenting identical anabolic properties to anabolic steroids in addition to marked reduced androgenic effects. These drugs have emerged in the doping area within the early 2000's. Ligandrol, ostarine, RAD-140 and andarine are the most popular agents belonging to this class. According to the world anti-doping agency (WADA) prohibited list, SARMs are prohibited at all times (i.e. in and out-of-competition) and are listed under the section S1.2 (other anabolic agents). The compilation of the WADA testing figures reports from 2015 to 2019 has indicated a regular increase of adverse analytical findings (AAF) due to SARMs, particularly with ostarine and ligandrol. The implementation of highly sensitive chromatographic anti-doping analyses has induced high-profile challenges of anti-doping rules violations as athletes have claimed in numerous occasions that contamination was the reason for their AAF. Since the early 2000's, it has been accepted by the Court of Arbitration for Sports (CAS) in Lausanne (Switzerland) that, under some specific circumstances, unusual explanations can be provided to the Panel to explain an AAF. This was the open door for forensic investigations, as it is done in criminal Courts. A forensic approach can include testing for SARMs in food, drinks, but mostly in dietary supplements. As most anti-doping rules violations are only known several weeks after urine collection, this biological matrix is seldom use for further tests, despite the fact that most SARMs can be detected for several weeks in urine. Luckily, hair or nail testing can be a complement to document the claim of the athlete but of course, it cannot be considered as an alternative to urinalysis. This is because a negative hair or nail result cannot exclude the use of the detected drug and cannot overrule the urine result. To date, all methods for SARMs identification in various matrices involve liquid chromatography coupled to tandem mass spectrometry or high-resolution mass spectrometry. The aim of this paper is to review the scientific literature on the analytical possibilities of testing SARMs in dietary supplements, urine and hair or nail clippings after an AAF to document the claims of an athlete or his/her legal team.