Selective Androgen Receptor Modulators (SARMs) are a class of investigational compounds that bind to androgen receptors in a selective manner. They are being studied for their potential ability to increase lean muscle mass and bone mineral density without the broader androgenic effects associated with traditional anabolic steroids. SARMs were originally developed with therapeutic intentions in conditions such as muscle wasting, osteoporosis, and age-related decline in bone density.

History and Development

Research on SARMs began in the late 1990s and early 2000s as scientists sought alternatives to testosterone therapy with fewer side effects. Early work focused on creating non-steroidal molecules capable of stimulating anabolic activity selectively in muscle and bone tissue. Several pharmaceutical companies have since conducted clinical trials to explore safety, efficacy, and potential medical applications.

• The review “Selective androgen receptor modulator development” notes that the first SARMs were reported in the late 1990s, and that considerable research efforts began thereafter. Lippincott Journals+PMC

• A paper titled “Discovery of the selective androgen receptor modulator MK‑0773 using a rational development strategy…” describes some of the early drug‑discovery work (ligands, structure‑activity relationships) that launched SARM development. PubMed

• The article “Development of selective androgen receptor modulators (SARMs) in the last two decades” traces how SARMs evolved from proof‑of‑concept compounds to clinical‑candidates targeting muscle‑wasting, osteoporosis, etc. PubMed

Mechanism of Action

Research indicates that after binding the AR in muscle and bone cells, SARMs trigger gene‑expression pathways for protein synthesis and bone remodelling (see Furuya et al.). Their proposed tissue‑selectivity may reflect reduced recruitment of certain AR co‑activators, minimal activation via 5α‑reductase pathways, and altered receptor conformations (Narayanan et al.). However, whether this selectivity leads to significantly fewer off‑target effects in humans remains unproven (see Narayanan et al., Androgen Receptor & Cardiovascular Disease review).

• Furuya et al. “Mechanism of the tissue‑specific action of the selective androgen receptor modulator S‑101479”. This study found that a SARM increased AR (androgen receptor) activity in bone cells, but with much lower AR dimerisation and different cofactor recruitment compared with natural androgen (DHT) — a mechanistic basis for tissue selectivity. PubMed

• Narayanan et al. “Selective androgen receptor modulators: a critical appraisal.” This review discusses how SARMs may achieve tissue selectivity via differences in metabolism (e.g., lack of 5α‑reductase conversion), differential coregulator recruitment and ligand‑induced conformational changes in the AR. PubMed

• “Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications” — reviews how SARMs enter the cytoplasm, bind AR, translocate to the nucleus, bind androgen‑response elements and influence gene transcription, while suggesting the real‑world tissue selectivity remains unproven. PubMed

• “Androgen Receptor and Cardiovascular Disease: A Potential Risk for the Abuse of Supplements Containing SARMs” — this article outlines the basic AR‐mediated mechanism for SARMs and notes that despite theoretical tissue selectivity, the translation into distinct safety profiles is still unclear. MDPI

Commonly Studied Compounds

Ostarine (MK-2866)
Studied for muscle wasting associated with cancer and aging. Clinical trials have explored its impact on lean body mass and physical function.

Ligandrol (LGD-4033)
Researched for muscle and bone-related disorders. Trials have examined its effect on strength and lean mass in short-duration studies.

Testolone (RAD-140)
Investigated for potential neuroprotective effects and anabolic activity. Human data is limited compared to other SARMs.

Andarine (S4)
Evaluated for osteoporosis-related applications. Anecdotal reports have noted visual side effects, though research remains preliminary.

S23
A more potent compound studied primarily in preclinical environments, particularly in reproductive suppression research.

MK-677 (Ibutamoren)
Frequently grouped with SARMs but technically a growth hormone secretagogue. It temporarily increases circulating growth hormone levels in research settings.

Clinical Research Status

To date, no SARM has received regulatory approval for therapeutic use. Most human trials have been early stage (Phase I or II), typically lasting several weeks to a few months, and focusing primarily on lean body mass, strength surrogate markers, and short‑term safety endpoints. Long‑term data (e.g., multi‑year observation, functional outcomes, extended safety) are still lacking, which is one reason why clinical validation and regulatory approval remain pending.

• A review titled “Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications” states: “Although there are currently no US Food and Drug Administration‑approved indications for SARMs…” PubMed

• The systematic review “Selective androgen receptor modulators (SARMs) as pharmacological treatment for muscle wasting in ongoing clinical trials” highlights that although SARMs have shown effects on lean body mass in Phase II trials, “long‑term outcomes have to be assessed” and efficacy on strength/function remains lacking. PubMed

• Another systematic review “Selective Androgen Receptor Modulators (SARMs) Effects on Physical Performance: A Systematic Review…” found that in nine studies (mean follow‑up ~80 days) they measured lean‐mass changes, but follow‑up durations remain short. PubMed

• A safety‑focused review “Selective androgen receptor modulator use and related adverse events including drug‑induced liver injury” emphasises the unknowns regarding long‑term exposure and possible adverse events. PMC

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Potential Therapeutic Uses (Under Investigation)

Scientists have explored SARMs for:

• Age-related muscle loss (sarcopenia)

• Cancer cachexia

• Osteoporosis and bone fragility

• Frailty following prolonged illness

• Mobility limitations in chronic disease

Evidence remains inconclusive, and further research is required before any therapeutic use is validated.

• Enobosarm (GTx‑024) and other SARMs have been investigated as treatments for muscle wasting (cachexia) in cancer. PubMed

• A systematic review found that SARMs improved lean body mass and body composition in trials including sarcopenia, cachexia and chronic illness, but with short follow‑ups and mixed functional outcomes. PubMed

• A mini‑review summarises that SARMs “may have an application in … muscle wasting, cancer cachexia, osteoporosis, frailty syndrome” (though these applications remain under‑investigated). europub.co.uk

Side Effects and Safety Considerations

Research and clinical observations have identified several potential risks. These may vary depending on compound, dose, duration, and individual biology:

• Suppression of endogenous testosterone production

• Changes in lipid profile (HDL reduction, LDL elevation)

• Potential liver strain based on liver enzyme elevations

• Mood or behavioral changes

• Visual disturbances reported with certain compounds

• Possible impacts on fertility

• Unknown long-term hormonal effects

Adolescents, pregnant individuals, and people with underlying health conditions are considered higher-risk populations in a research context. Multi-year safety data does not yet exist.

• Metabolic and hormonal dysfunction in asymptomatic patient using selective androgen receptor modulators: a case report: Documents a case where use of SARMs (LGD‑4033 and S‑23) was associated with elevated liver enzymes, suppression of the pituitary–gonadal axis, and adverse changes in lipid profile. SpringerOpen

• GSK2881078, a SARM, Produces Dose‑Dependent Increases in Lean Mass in Healthy Older Men and Women: Shows that dosing a SARM caused reductions in HDL cholesterol and reductions in endogenous testosterone levels. OUP Academic

• Androgen Receptor and Cardiovascular Disease: A Potential Risk for the Abuse of Supplements Containing Selective Androgen Receptor Modulators: Reviews the risk of cardiovascular disease linked to SARM misuse, including mechanisms like altered lipid profiles, hormonal disruption and other cardiovascular pathways. PMC

• Effect of Selective Androgen Receptor Modulator on Cholesterol Efflux Capacity, Size, and Subspecies of HDL Particles: Demonstrates how an oral SARM suppressed HDL‑C and altered HDL particle and apolipoprotein subclasses — supporting your point about lipid profile changes. PubMed

• Athlete Selective Androgen Receptor Modulators Abuse: A Systematic Review: Covers many of the areas you mention — testosterone suppression, liver injury, long‑term unknowns, and the limited state of research. PubMed

Regulatory and Legal Status

Regulatory agencies classify SARMs as investigational drugs. They are not approved for muscle building, athletic enhancement, or recreational use. In many regions, selling SARMs as dietary supplements or for human consumption is prohibited. The World Anti-Doping Agency (WADA) includes SARMs on its list of banned substances, and athletes have received sanctions following detection in anti-doping tests.

Regulations may differ internationally and are subject to change.

• U.S. Anti‑Doping Agency (USADA) — “Selective Androgen Receptor Modulators (SARMs)”: confirms that all SARMs are investigational drugs, none are approved for human use, and they are prohibited at all times by World Anti‑Doping Agency (WADA). NPC Hello

• U.S. Food & Drug Administration (FDA) — “FDA Warns of Use of Selective Androgen Receptor Modulators (SARMs) Among Teens & Young Adults”: notes that SARMs are unapproved drugs, cannot legally be marketed as dietary supplements, and highlights the risks of human consumption. U.S. Food and Drug Administration

• UK regulatory coverage — “SARMs Legalities in the UK” : explains that in the UK SARMs have not been authorised for sale for human consumption and are treated under novel‑foods / drug regulation frameworks.

• WADA’s Prohibited List — lists SARMs under S1.2 “Other anabolic agents”, explicitly naming them as banned substances in sport. World Anti-Doping Agency

• Australian regulation example — “Banned substances in sports supplements” (ACT Gov): clarifies SARMs are not registered for medical use and are illegal to supply as supplements in Australia. act.gov.au

Quality Control Concerns

Because SARMs are not approved consumer medications, products labeled as SARMs may vary significantly in purity. Independent testing in past research reports has revealed:

• “Analysis of supplements available to UK consumers purporting to contain selective androgen receptor modulators” — found a range of discrepancies in products labelled as SARMs (mis‑labelling, undeclared substances, incorrect concentrations). PubMed+choice.wetestyoutrust.com

• “Illegal products containing selective androgen receptor modulators purchased online from Italy: health risks for consumers” — demonstrated issues of contamination, mis‑labelling, undeclared active substances, and wide variation in concentrations. Semantic Scholar

• “Rapid detection of illegal selective androgen receptor modulators in unregistered supplements …” — found that in about half of the unregistered supplements analysed, the declared SARM was absent or present at incorrect dose. PubMed

• A review on SARM‑related adverse events including a section on “labels often do not provide accurate information for consumers … analytical tests have confirmed many discrepancies in both quantity and quality analysis.” PMC

• A European market surveillance summary: “Products containing these substances may be mis‑advertised as muscle‑boosting supplements though they are unapproved, and may contain unknown or illicit active ingredients.” edqm.eu

SARMs vs. Anabolic Steroids

While both interact with androgen receptors, key differences exist:

• Steroids are broader in effect and influence multiple tissues, often leading to androgenic side effects such as prostate enlargement, hair loss, and liver strain.

• SARMs are designed to be tissue-selective, although research is still evaluating how effective that selectivity is in practice.

Comparative long-term safety remains unclear.

SARMs in Athletics & Sport

Anti-doping authorities report an increase in sanctions related to SARMs due to:

• Their oral bioavailability

• Short-term performance effects suggested in limited studies

• Online availability

Detection methods have improved, and trace amounts can be identified through modern chromatographic techniques. Consequences vary by league and jurisdiction.

For the latest rules and prohibited substance lists, check with official anti-doping organizations:

• UK: UKAD (UK Anti-Doping)

• USA: USADA (U.S. Anti-Doping Agency)

• Global: WADA (World Anti-Doping Agency)

Ethical Considerations

Fairness in competitive sports

• “Controversial supplements and emerging doping alternatives in sports: A critical review of evidence, safety, and detection challenges” – discusses how emerging substances (including SARMs) raise ethical issues because access may be unequal and they undermine a level playing field. ResearchGate

• “Ethical Considerations in Sports Competition” – overview article on how the use of performance-enhancing drugs (PEDs) threatens fair play, integrity, and the spirit of competition. dashsports.org

Influence on younger individuals exposed to performance pressures

• The review from turn0search4 also addresses how athletes (especially younger/less experienced) may be vulnerable to marketing of untested substances, and the ethical concern about informed consent and pressure. ResearchGate

• “The ethics of performance-enhancing drugs in competitive sports” – explores broader ethical arguments including how sports culture and external pressure can lead to risky behaviour among athletes. multidisciplinaryfrontiers.com

Potential normalization of experimental drugs in fitness culture / Social media dissemination of non-evidence-based claims

• The Wikipedia entry on SARMs mentions their marketing via online/grey-market channels and how social media and internet availability play a role in non-medical use. Wikipedia

• The same critical review (turn0search4) points out how novel compounds marketed to athletes may lack full evidence, yet get normalized in fitness/enhancement culture and present ethical issues. ResearchGate

Accessibility outside clinical oversight

• The review (turn0search4) again: it states that emerging substances like SARMs and peptides are used outside regulated clinical contexts, raising ethical concerns about athletes effectively becoming ‘guinea pigs’. ResearchGate

• “Legal and Ethical Considerations of PED Use in Sports” – article outlines how availability, regulation and enforcement vary globally, and how non-medical use poses challenges. EDC.ASIA

Long-Term Unknowns

1. Impact on cardiovascular health

• U.S. Food & Drug Administration – “FDA Warns of Use of Selective Androgen Receptor Modulators (SARMs) Among Teens & Young Adults” – notes that studies and reports show SARMs are associated with serious or life-threatening health problems, such as increased risk of heart attack or stroke. U.S. Food and Drug Administration

• Review: Androgen Receptor and Cardiovascular Disease: A Potential Risk for the Abuse of Supplements Containing Selective Androgen Receptor Modulators – explores how SARMs may increase cardiovascular disease risk through effects on renin-angiotensin system, smooth muscle cells, platelet activity, lipid profile and more; and emphasises the paucity of long-term clinical trials. PMC

2. Persistent hormonal suppression

• Selective Androgen Receptor Modulators: A Mini‑Review – mentions suppressive effects of some SARMs on gonadotrophin secretion in animal models (rats), pointing to potential fertility / hormonal-axis concerns. Lupine Publishers

• Also from the US Pharmacist article: “SARMs have been found to reduce endogenous testosterone …” U.S. Pharmacist

3. Fertility outcomes

• The mini-review above (as above) touches on gonadotrophin suppression, which implicates fertility risk. Lupine Publishers

• The FDA warning also flags infertility as a reported concern. U.S. Food and Drug Administration+1

4. Bone density effects after discontinuation

• Selective Androgen Receptor Modulator Treatment Improves Muscle Strength and Body Composition and Prevents Bone Loss in Orchidectomized Rats – While showing bone-density preservation in animal models, the paper also implies that effects after discontinuation (in non-therapeutic use) remain under-studied. OUP Academic

• The review “Selective Androgen Receptor Modulators: the future of androgen therapy” states that long-term safety issues including effects beyond the study durations remain to be explored. Translational Andrology and Urology

5. Cancer-related risk

• While direct long-term cancer risk data for SARMs is lacking, the narrative pieces (e.g., Cleveland Clinic article) flag “unknown” or “not fully characterised” risks including potential long-term organ/ tissue harms. health.clevelandclinic.org

Frequently Asked Questions

Are SARMs approved for medical use?
As of now, no SARMs are approved for general medical treatment of muscle growth.

Are SARMs legal to use in sports?
Anti-doping organizations prohibit them. Athletes have received sanctions for positive tests.

Are SARMs safer than steroids?
Research suggests a potentially reduced side-effect profile in short-term studies, but long-term data is lacking.

Are SARMs considered supplements?
Regulators do not recognize SARMs as dietary supplements. When marketed as such, products are often considered misbranded.

Do SARMs have long-term human studies?
Extended clinical data over multiple years is not yet available.

Research & Expert Contributions on SARMs

Scientific research on SARMs and their detection in sports continues to evolve, driven by the work of several leading scientists in the fields of anti-doping and sports medicine. Below are some notable contributors whose studies have shaped current understanding of how SARMs are identified, regulated, and used in athletic settings.

• Professor Mario Thevis – Based at the German Sport University Cologne, Thevis is a leading expert in anti-doping science. His work focuses on developing analytical methods to detect SARMs in athletes’ samples.

  Example study: Detection of SARMs in Doping Control Analysis

  Thevis has also collaborated with Professor Wilhelm Schänzer, another authority in doping control research, on WADA-funded studies examining the metabolism of SARMs.

 

• Dr. Pascal Kintz – A forensic toxicologist from France, Kintz has published on real-world doping cases involving SARMs, including how such findings are handled from a forensic perspective.

Key paper: The Forensic Response After an Adverse Analytical Finding Involving a SARM

• Dr. Nikhil Vasireddi and colleagues (USA) – Authors of a recent systematic review that summarizes SARM misuse among athletes and recreational users, providing insight into patterns of use and health implications.

Review: Athlete Selective Androgen Receptor Modulator Abuse: A Systematic Review

 

These researchers’ work underpins much of what is known today about SARMs in sport — from laboratory detection methods to understanding misuse trends and regulatory responses. Their findings help shape global anti-doping policies and raise awareness about the risks of unregulated use.

Conclusion

SARMs represent an active area of research with potential therapeutic applications in muscle and bone-related conditions. However, their regulatory status, side-effect profile, unknown long-term impacts, and quality-control concerns have led to significant caution within the medical and athletic communities. Ongoing clinical trials and safety evaluations will determine whether SARMs eventually receive approval for therapeutic use.

Author

By Dr. Larry Bowers, PhD – Anti-Doping Scientist and Researcher, U.S. Anti-Doping Agency (USADA)