Selective androgen receptor modulators, commonly called SARMs, are a class of experimental drugs designed to activate androgen receptors in muscle and bone while largely sparing tissues like the prostate and skin. But the term “SARMs” covers a wide range of chemically distinct compounds, and they are not interchangeable. Ostarine, ligandrol, RAD140, andarine, YK11, and S23 each have different structures, different potencies, different tissue preferences, and different risk profiles. None are approved for human use by any major regulatory agency, yet they circulate widely on the gray market, often under the fiction of being “research chemicals.”
How SARMs Achieve Tissue Selectivity
Traditional anabolic steroids bind to androgen receptors throughout the body and get converted by enzymes into other hormones, which is why they tend to grow muscle but also enlarge the prostate, cause acne, and accelerate hair loss. SARMs sidestep much of that because they are not converted by aromatase (into estrogen) or by 5-alpha reductase (into dihydrotestosterone). The exact mechanism behind their tissue selectivity is still being worked out, but research points to something called the coactivator hypothesis: when a SARM binds to an androgen receptor, it bends the receptor into a shape that attracts a different mix of helper proteins than testosterone or DHT would.
In prostate tissue, for instance, an aryl propionamide SARM was found to recruit both coactivator and corepressor proteins to the receptor, producing only a weak overall signal. In skeletal muscle, the same SARM preferentially recruited coactivators, producing a strong anabolic signal.
1Korean Journal of Sports Medicine. The Mechanisms of Anabolic Steroids, Selective Androgen Receptor Modulators and Myostatin Inhibitors A separate study of the SARM S-101479 confirmed this pattern in bone cells: the compound boosted bone-building activity in osteoblast cell lines as effectively as DHT, despite recruiting far fewer cofactors to the androgen receptor. It failed to recruit the classical p160 coactivator family entirely but still achieved its anabolic effects through a smaller subset of cofactors.2Biological and Pharmaceutical Bulletin. Mechanism of the Tissue-Specific Action of the Selective Androgen Receptor Modulator S-101479
The practical takeaway: different SARMs bend the androgen receptor differently, which is why each compound has its own profile of tissues it strongly activates, weakly activates, or mostly ignores. That structural quirk is the entire basis for the diversity among SARMs.
Ostarine (Enobosarm, MK-2866)
Ostarine is the most extensively studied SARM in clinical trials. Developed originally by GTx under the name enobosarm, it reached phase II and phase III trials for cancer-related muscle wasting. In a randomized, double-blind phase II trial of cancer patients with cachexia, both the 1 mg and 3 mg daily doses produced significant increases in lean body mass over roughly four months. The 1 mg group gained a median of 1.5 kg of lean mass, while the placebo group showed essentially no change.3PubMed Central. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial The researchers noted that these improvements came without the toxic effects typically associated with androgens or progestational agents.
In animal studies, ostarine has also shown potential for bone health. In a rat model of osteoporosis caused by removing the testes, prophylactic ostarine treatment helped preserve both cortical and trabecular bone density compared to untreated animals. However, the therapy group (treated after bone loss had already begun) saw more limited gains, mostly in cortical femoral density.4PubMed Central. Treatment of osteoporosis using a selective androgen receptor modulator ostarine in an orchiectomized rat model One notable caveat from that study: the prophylaxis group showed increased prostate weight, a sign that ostarine’s tissue selectivity is not absolute.
Among recreational users, ostarine is often considered a “mild” SARM, partly because it was the first to be widely available and partly because its clinical doses are low. But “mild” is relative. It still suppresses natural testosterone production and has been linked to liver injury, particularly during or after post-cycle therapy.
Ligandrol (LGD-4033)
Ligandrol is another frequently encountered SARM, studied in a phase I trial involving healthy young men. In that trial, lean body mass increased in a dose-dependent fashion, meaning higher doses produced larger gains. Fat mass, on the other hand, did not change significantly at any dose. Ligandrol also showed a long elimination half-life, which means it accumulates in the body over repeated dosing.5PubMed Central. The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Oral, Selective Androgen Receptor Modulator, in Healthy Young Men
On the gray market, ligandrol is often positioned as a step up from ostarine in terms of potency, and the clinical pharmacology supports that perception to some extent. The dose-dependent lean mass gains were observed in a short trial window, and its longer half-life makes it pharmacologically “stickier.” It has also appeared in liver injury case reports involving recreational users, particularly in the context of post-cycle therapy with anti-estrogen drugs.6PubMed Central. Liver injury associated with the use of selective androgen receptor modulators and post-cycle therapy: Two case reports and literature review
RAD140 (Testolone)
RAD140 stands out from most other SARMs in that its research has branched into two very different directions: oncology and neuroprotection. In breast cancer models, RAD140 bound androgen receptors with high affinity and inhibited the growth of tumors that were positive for both androgen and estrogen receptors. It appeared to work by activating the androgen receptor pathway while suppressing the estrogen receptor pathway, including suppression of the ESR1 gene itself.7PubMed. Selective Androgen Receptor Modulator RAD140 Inhibits the Growth of Androgen/Estrogen Receptor-Positive Breast Cancer Models with a Distinct Mechanism of Action
On the neuroprotection side, RAD140 was as effective as testosterone at reducing neuron death in cultured hippocampal cells exposed to toxic insults. When tested in live rats with brain lesions caused by the excitotoxin kainate, RAD140 still showed protective effects on hippocampal neurons while largely sparing prostate tissue from androgenic stimulation.8PubMed Central. Selective androgen receptor modulator RAD140 is neuroprotective in cultured neurons and kainate-lesioned male rats The researchers described these as preliminary findings relevant to neurodegenerative diseases. That said, no human trials on RAD140 for neuroprotection have been published.
Among recreational users, RAD140 is considered one of the more potent SARMs. It has also appeared in case reports of gynecomastia and suppressed testosterone when taken as an ingredient in commercial “performance-enhancing” supplements.9JCEM Case Reports. Reversible Gynecomastia and Hypogonadism Due to Usage of Commercial Performance-Enhancing Supplement Use
Andarine (S4) and Its Role in Bone Research
Andarine, often labeled S4 online, was one of the earlier SARMs to be characterized. In ovariectomized rats (a standard model for postmenopausal bone loss), andarine treatment maintained whole-body and trabecular bone mineral density, preserved cortical bone content, increased bone strength, and reduced body fat.10PubMed Central. Selective Androgen Receptor Modulator (SARM) Treatment Prevents Bone Loss and Reduces Body Fat in Ovariectomized Rats A related SARM, S-40503, demonstrated that the anabolic bone effects could surpass what estrogen achieves: it directly stimulated new bone formation on the periosteal surface, something estrogen (which mainly slows bone resorption) did not do.11Biological and Pharmaceutical Bulletin. Bone Anabolic Effects of S-40503, a Novel Nonsteroidal Selective Androgen Receptor Modulator (SARM), in Rat Models of Osteoporosis
These bone findings are one of the reasons the pharmaceutical industry invested heavily in SARMs. Osteoporosis is a massive unmet medical need, and the idea of a pill that builds bone without triggering prostate growth or masculinization in women is genuinely appealing. But andarine never advanced past animal studies, and its gray-market use comes with the usual disclaimers: no reliable human safety data, uncertain dosing, and questionable product quality.
YK11 and S23
YK11 occupies an unusual niche. Structurally, it is steroidal rather than nonsteroidal like most other SARMs, and it has a mechanism of action that goes beyond simple androgen receptor activation. In cell culture, YK11 induced muscle cell differentiation similarly to DHT, but it also triggered expression of follistatin, a protein that inhibits myostatin. Myostatin is the body’s brake on muscle growth, so increasing follistatin is, in theory, like cutting the brake lines. Blocking the YK11-induced follistatin with an antibody reversed the muscle-building effect, suggesting follistatin production is central to how YK11 works.12PubMed. Selective androgen receptor modulator, YK11, regulates myogenic differentiation of C2C12 myoblasts by follistatin expression DHT did not trigger this follistatin response, which makes YK11’s mechanism genuinely distinct.
S23 has been researched in a completely different context: male contraception. In intact male rats treated with S23 combined with estradiol, the compound suppressed luteinizing hormone and follicle-stimulating hormone, leading to a dramatic reduction in sperm production. In one experiment, four out of six animals in the treatment group had no detectable sperm, and mating trials produced zero pregnancies. After treatment stopped, fertility returned fully within about 100 days.13PubMed Central. Preclinical characterization of a (S)-N-(4-cyano-3-trifluoromethyl-phenyl)-3-(3-fluoro, 4-chlorophenoxy)-2-hydroxy-2-methyl-propanamide: a selective androgen receptor modulator for hormonal male contraception Compared with other SARMs, S23 showed an unusually strong ability to suppress gonadotropin levels, making it behave more like a potent androgen in the hormonal axis while still showing some tissue selectivity in peripheral tissues.14PubMed. A selective androgen receptor modulator for hormonal male contraception No human trials on S23 have been published.
Compounds That Are Not Actually SARMs
A persistent source of confusion in the gray market is that several popular compounds are sold alongside SARMs, marketed as SARMs, and discussed in the same forums, but are pharmacologically unrelated. MK-677 (ibutamoren) is a growth hormone secretagogue. It stimulates the release of growth hormone and insulin-like growth factor 1, but it does not touch the androgen receptor. Cardarine (GW501516) is a PPAR-delta agonist that affects fat metabolism and endurance but, again, has nothing to do with androgen signaling.15JCEM Case Reports. Reversible Gynecomastia and Hypogonadism Due to Usage of Commercial Performance-Enhancing Supplement Use These are distinct drug classes that happen to share shelf space with SARMs in the performance-enhancement ecosystem.16PubMed. SARMs, Metabolic Modulators and Growth Hormone Secretagogues in Suspected Illegal Medicines, Bought as Sport Performance Enhancers
This matters because someone who takes MK-677 thinking it is a SARM will experience a completely different set of effects and side effects. Growth hormone secretagogues tend to cause water retention, increased appetite, and elevated blood sugar. Cardarine’s development was abandoned partly because of cancer concerns in long-term rodent studies. Lumping them all together as “SARMs” leads to confusion about what to expect and what risks are actually on the table.
Side Effects and Organ Risks
The recreational perception that SARMs are “safer than steroids” deserves serious scrutiny. A cross-sectional survey of over 500 respondents found that more than half of the 343 participants who admitted using SARMs reported significant adverse effects, including mood swings, decreased testicular size, and acne.17Nature. Adverse effects and potential benefits among selective androgen receptor modulators users: a cross-sectional survey Those side effects are familiar to anyone who knows anabolic steroids, which undermines the narrative that SARMs are a clean alternative.
Liver injury is a specific concern. Case reports document cholestatic liver damage in amateur athletes using ligandrol or ostarine, particularly after stopping the SARM and beginning post-cycle therapy with anti-estrogen drugs like tamoxifen or clomiphene. The clinical picture in those cases involved jaundice, fatigue, and very high bilirubin levels, with liver biopsies showing bile plugging and loss of bile ducts.18PubMed Central. Liver injury associated with the use of selective androgen receptor modulators and post-cycle therapy: Two case reports and literature review Recovery was prolonged. One review characterized SARMs as an “emerging liver toxin” and noted that concomitant use of post-cycle therapy drugs complicates the picture, making it hard to separate which substance caused the damage.19PubMed Central. Selective Androgen Receptor Modulators: An Emerging Liver Toxin
On the cardiovascular side, SARMs consistently suppress HDL cholesterol. In a clinical trial using escalating doses, HDL cholesterol dropped significantly with SARM treatment, and apolipoprotein A-I (the main protein in HDL particles) was also suppressed. Hepatic lipase activity increased, which can accelerate HDL clearance from the blood.20PubMed Central. Effect of Selective Androgen Receptor Modulator on Cholesterol Efflux Capacity, Size, and Subspecies of HDL Particles Whether this translates to increased heart disease risk over the long term is unknown, because no long-term cardiovascular outcome data exist for any SARM. In monkey studies, a different SARM (SARM-2f) showed a lipid profile that differed from what testosterone produces, with all plasma lipid levels either decreased or trending downward.21PubMed Central. A selective androgen receptor modulator SARM-2f activates androgen receptor, increases lean body mass, and suppresses blood lipid levels in cynomolgus monkeys So the lipid effects are not uniform across all SARMs, and the compound-specific differences matter.
What Is Actually in the Bottle
Even if a particular SARM were completely benign at its stated dose, the product you buy online may not contain what the label says. This is one of the most consistent findings across product-testing studies. An analysis of supplements sold in the UK found discrepancies ranging from products with no active ingredients at all to products containing undeclared prohibited substances. Where SARMs were detected, the actual concentrations often differed from what the packaging claimed.22PubMed. Analysis of supplements available to UK consumers purporting to contain selective androgen receptor modulators
An Australian study of 111 SARM products found that while 94 correctly identified the active ingredient on the label, 90 of those were contaminated with other performance-enhancing drugs. Only 34 out of 111 products met quality standards for both identity and dosage accuracy.23Performance Enhancement & Health. “For research use only”: A comprehensive analysis of SARMs and related IPEDs purchased on local Australian websites between 2017 and 2018 Italian researchers found an even more alarming picture: in roughly a quarter of samples tested, the expected SARM was not present at all but had been replaced by a different one. Undeclared pharmaceutical substances including tamoxifen, testosterone, and tadalafil showed up in about a third of products, and measured doses ranged from 30% to 90% of what the label claimed.24Oxford Academic. Illegal products containing selective androgen receptor modulators purchased online from Italy: health risks for consumers
This means that when someone reports their experience with “ostarine” or “RAD140,” they may not have taken ostarine or RAD140 at all, or they may have taken it alongside testosterone, anti-estrogen drugs, or completely unknown fillers. It makes self-reported user experiences unreliable and makes any kind of informal risk assessment nearly impossible.
Anti-Doping Detection
All SARMs are prohibited by the World Anti-Doping Agency under the category of “other anabolic agents.” The detection methods have become quite sophisticated. Doping-control laboratories use liquid chromatography coupled to mass spectrometry to identify a wide range of SARM pharmacophores, including ostarine, LGD-4033, RAD140, andarine, YK11, and many others.25PubMed. Detection of SARMs in doping control analysis Newer methods can detect SARMs and their metabolites not just in urine and blood but in dried blood spots, hair, and nail samples, extending the detection window well beyond what older tests could catch.26PubMed. Advances in SARMs anti-doping analysis
SARM use is not limited to elite sport. Swedish healthcare laboratories have begun using WADA-accredited screening methods to detect SARMs in samples from the general population, reflecting concern that recreational use has grown well beyond gym culture and into broader public health territory.27PubMed. Detection of anabolic agents including selective androgen receptor modulators in samples outside of sport Given the product adulteration data, athletes who claim accidental SARM exposure through contaminated supplements have a plausible (if not always convincing) defense. But the testing infrastructure is now robust enough that evading detection is increasingly difficult regardless of the compound chosen.
The Clinical Pipeline Versus the Gray Market
There is a striking disconnect between how SARMs are discussed in the bodybuilding world and where the actual science stands. The compound with the most clinical data is ostarine, which has been tested in cancer cachexia patients and has shown consistent lean-mass improvements along with a lower hazard ratio for survival in cancer populations.28PubMed Central. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial Yet even ostarine has not gained regulatory approval. Its phase III trials for muscle wasting did not meet all primary endpoints, and the FDA has not authorized it.
Ligandrol has one published phase I safety trial in healthy men. RAD140 has preclinical data in breast cancer models and rat neuroprotection studies. YK11 and S23 have only cell culture and rodent data. Newer compounds like ACP-105 have been characterized mostly through computational modeling rather than animal or human studies.29PubMed Central. In Silico First multifaceted ADME profile of ACP-105 The gap between the certainty with which these compounds are discussed in forums and the thinness of their actual evidence base is enormous. People are making dosing decisions about drugs that, in some cases, have never been given to a human being in a controlled setting.
The pharmaceutical interest in SARMs remains real but cautious. Muscle wasting, osteoporosis, sarcopenia in the elderly, and hypogonadism without prostate risk are all areas where a well-characterized SARM could fill a genuine medical gap. The tissue-selectivity principle has been validated in preclinical work across multiple compounds. But translating that into an approved therapy requires showing both efficacy and safety in large human trials, and that process has been painfully slow for every SARM that has entered it.