S23: What the Research Actually Shows About This SARM

Key takeaways

What Is S23?

S23 (chemical name (S)-3-(4-chloro-3-fluorophenoxy)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-2-methylpropanamide) is a non-steroidal aryl-propionamide compound belonging to the class of drugs known as selective androgen receptor modulators, or SARMs. It was characterized in laboratory research as part of a series of androgen receptor ligands developed to study tissue-selective androgen activity in rodents. S23 has never been approved for any human or veterinary use, and every commercial source that sells it explicitly states that it is not intended for human consumption.

Receptor Binding and Mechanism

The core pharmacological finding on S23 comes from a study published in Endocrinology in 2009, which characterized the compound in male rats as a candidate for hormonal male contraception. That study reported that <cite index="26-2">S-23 showed high binding affinity (inhibitory constant = 1.7 ± 0.2 nm) and was identified as a full agonist in vitro.</cite> This places its affinity for the androgen receptor above that of several other investigational SARMs, though direct comparisons across studies are complicated by differences in assay methods.

Multiple chemical supplier product sheets, which cite the same underlying pharmacology data, similarly describe S-23 as binding the androgen receptor with a Ki of 1.7 nM and inducing androgen-receptor-mediated transcriptional activity in cell culture.

Preclinical Findings on Muscle and Bone

In the same rat study, <cite index="26-9">S-23 increased bone mineral density and lean mass but reduced fat mass in a dose-dependent manner.</cite> These findings are the basis for interest in S23 as a tool compound for studying androgen-driven anabolism in bone and skeletal muscle.

S23's tissue selectivity, however, is only partial rather than absolute. Product data sheets from chemical suppliers report that S-23 increases prostate, seminal vesicle, and levator ani muscle weights in castrated rats, meaning it activates classic androgen-responsive reproductive tissues in addition to muscle. The original characterization study quantified this directly: <cite index="26-3">in castrated male rats, the ED50 of S-23 in the prostate and levator ani muscle was 0.43 and 0.079 mg/d, respectively</cite>, indicating that androgenic tissues respond to even lower doses than the anabolic tissue in that model. In intact rats over a short treatment course, the pattern was more tissue-specific: <cite index="26-4">in intact male rats treated for 14 d, S-23 alone suppressed LH levels by greater than 50% at doses greater than 0.1 mg/d, with corresponding decreases in the size of the prostate but increases in the size of levator ani muscle.</cite> All of this evidence comes from rodents; no controlled human study has measured muscle mass, strength, bone density, or body composition outcomes with S23.

Male Contraception Research in Rats

S23 has drawn particular scientific interest because of hormone-suppressing effects observed in male rats, which researchers investigated as a potential basis for a hormonal male contraceptive. It is important to be precise about what the original study found, because it is frequently overstated in secondary sources.

When S-23 was given alone to intact rats, it suppressed luteinizing hormone but produced only mixed effects on the testis and epididymis. Full suppression of fertility required combining S-23 with estradiol benzoate, which researchers added because it was necessary to maintain normal mating behavior in the animals. Over a 10-week course of this combination, <cite index="26-5,26-6">S-23 showed biphasic effects on androgenic tissues and spermatogenesis by suppressing serum concentrations of LH and FSH; EB alone showed no effect on spermatogenesis.</cite> Under this combined regimen, <cite index="26-7">in the EB + S-23 (0.1 mg/d) group, four of six animals showed no sperm in the testis and zero pregnancies (none of six) in mating trials.</cite> This means the effect was substantial but not uniform across every treated animal, and it depended on co-administration with estradiol rather than S23 alone.

The suppression was reversible. <cite index="26-8">After termination of treatment, infertility was fully reversible, with a 100% pregnancy rate observed after 100 d of recovery.</cite> The study authors concluded that this was <cite index="26-10">the first study to show that a selective androgen receptor modulator combined with EB is an effective and reversible regimen for hormonal male contraception in rats</cite>, and they described S-23's properties as making it <cite index="26-11">a strong candidate for use in oral male contraception</cite> in that animal model. This research program was never advanced into human clinical trials, and no human contraceptive study of S23 has been published.

Absence of Human Data

Every effect described above comes from rodent experiments conducted with laboratory-grade S23 under controlled dosing, monitoring, and husbandry conditions. No peer-reviewed human clinical trial of S23 has been published, so there is no clinical evidence describing its effects, pharmacokinetics, dosing, or safety profile in people. Anecdotal reports from individuals who purchase unregulated "research chemical" products online do not constitute clinical evidence and cannot substitute for controlled human studies.

Legal Status, Doping Rules, and Regulatory Position

No SARM, including S23, is approved by the FDA for any human use, and SARMs cannot be legally marketed as dietary supplements or drugs in the United States. The FDA has stated plainly that products marketed as SARMs <cite index="38-6,38-7">are generally marketed as dietary supplements, they are not dietary supplements. Instead, these products are unapproved drugs that FDA has not reviewed for safety and effectiveness.</cite> The agency has also confirmed that <cite index="38-1">FDA has issued warning letters to companies selling unapproved products marketed as SARMs over the years and has pursued criminal actions against distributors of these products.</cite>

The World Anti-Doping Agency prohibits SARMs as a class, and S23 is named specifically as an example in the current Prohibited List. WADA's list groups the class as <cite index="47-1,47-2">selective androgen receptor modulators [SARMs, e.g. andarine, enobosarm (ostarine), LGD-4033 (ligandrol), RAD140, S-23 and YK-11] ... All prohibited substances in this class are non-Specified Substances</cite>, and this category falls under <cite index="44-5,44-6">the world anti-doping agency (WADA) prohibited list, [where] SARMs are prohibited at all times (i.e. in and out-of-competition) and are listed under the section S1.2 (other anabolic agents), a section that also contains clenbuterol.</cite> Peer-reviewed forensic toxicology literature reviewing WADA testing statistics has reported that <cite index="44-7">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</cite>, reflecting continued availability of these compounds through unregulated online sales even though they are banned in sport.

S23 specifically has been flagged as a concern for doping-control laboratories. A 2024 study developed methods to detect S-23 and its metabolites in horses used in competitive racing, noting that <cite index="31-3">S-23, an arylpropionamide selective androgen receptor modulator, presents a significant threat to sports doping</cite>. In that study, researchers reported that <cite index="31-1,31-2">S-23 was the most abundant analyte detected for both horses, allowing detection for up to 143 h post-administration, [in what is] to the best of the authors' knowledge, the first report of S-23 and metabolites in equine urine and plasma samples.</cite> This work extends earlier doping-control research on related SARMs and demonstrates that laboratories have developed analytical methods capable of identifying S23 use, even though it has not been the subject of a controlled human trial.

Products marketed online as S23 are typically labeled "for research purposes only" or similar, a labeling practice that sellers use in an attempt to avoid FDA regulatory requirements that apply to drugs intended for human consumption, even though these products are commonly purchased and used by people seeking muscle-building or performance effects. Because this market is unregulated, there is no independent assurance of the identity, purity, or actual dose contained in any product sold this way.

Documented Harms of the SARM Class

Because no controlled human trial of S23 itself exists, the closest available evidence proxy for human risk is data on the broader SARM class, gathered mostly from case reports and the FDA's adverse event monitoring. The FDA states that <cite index="38-8">life-threatening reactions, including liver injuries that required hospitalization, have occurred in people taking products containing SARMs</cite>. Summarizing the FDA's warnings, a 2023 report noted that <cite index="36-4">SARMs have been associated with increased risk of heart attack or stroke, psychosis, sleep disturbances, sexual dysfunction, liver injury/failure, infertility, pregnancy miscarriage and testicular shrinkage</cite>.

Case-level clinical literature reviewing SARM misuse has also described serious musculoskeletal and cardiac complications. One review of published cases reported that <cite index="16-5,16-6,16-7">an increasing number of cases of liver damage due to the misuse of SARMs were reported during the period 2020–2024… cases of myocarditis, rhabdomyolysis, gynecomastia, and tendon rupture have been documented in amateur users of SARMs</cite>, concluding plainly that <cite index="16-9">SARMs are not safe, and measures must be taken to control and regulate their online trade</cite>. These harms have been documented across the SARM class broadly; case reports specific to S23 in humans have not been published, which reflects the near-total absence of controlled human exposure data rather than evidence that S23 is safer than other class members. Given its high receptor affinity and pronounced hormonal suppression in animal studies, there is no basis in the literature to assume S23 would be better tolerated in people than other SARMs already linked to these harms.

Bottom Line

S23 is a potent, high-affinity androgen receptor agonist that has produced measurable anabolic effects on bone and muscle and pronounced, reversible suppression of male fertility in rat studies, particularly when combined with estradiol. None of this has been replicated or tested in a published human clinical trial. It is not approved by the FDA for any use, cannot legally be sold as a supplement or drug in the United States, and is prohibited in sport by WADA, which names it explicitly under its ban on SARMs. Products sold online as S23 are unregulated research chemicals, and the documented harms associated with the SARM class as a whole, including liver injury, cardiovascular events, and psychiatric effects, mean that any use of S23 outside of a formal research setting carries risks that have not been characterized or ruled out.

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