SARMs

Investigational drugs designed to stimulate androgen receptors in muscle and bone while sparing other tissues — the pharmaceutical goal was steroid benefits without steroid side effects. None has completed development; several were abandoned mid-trial.

SARMs bind the same androgen receptor testosterone does, but they are built to activate it strongly in muscle and bone while activating it weakly in the prostate, skin and hair follicle. The selectivity comes from the shape of the molecule changing which co-regulator proteins get recruited once it docks. That is the theory, and it is a genuine pharmacological idea, not marketing. The gap between theory and reality is that selectivity is relative rather than absolute, none of these compounds has completed the trials that would establish where the line actually falls in humans, and the liver and cholesterol effects seen in practice show the tissue selectivity does not extend as far as the sales pitch implies.

Early-phase human trials (ostarine, LGD-4033) show real but MODEST lean-mass gains — a few pounds over weeks, far below what steroid trials show. The "selective" promise is only partially borne out: testosterone suppression appears in trials at higher doses. Development stalled largely because effects didn't justify risks to sponsors.

• Several SARMs reached phase 2 trials in cancer cachexia, age-related muscle loss and stress urinary incontinence. Ostarine (enobosarm) has the most human data of any of them.
• Lean-mass changes were measurable but modest. The most-cited ligandrol study was a 21-day phase I trial in 76 healthy men whose primary aims were safety, tolerability and pharmacokinetics — lean mass, strength, lipids and hormones were exploratory outcomes, not established efficacy. Evidence quality differs sharply by compound and is absent for most of the research chemicals sold under this banner.
• No SARM is approved anywhere for any indication. Several programmes failed or were abandoned, though enobosarm remains under active investigation. The POWER phase III trials enrolled 641 patients between them against co-primary lean-mass and stair-climb-power endpoints, and did not consistently meet both — the lean mass gained did not reliably become functional benefit, which is the recurring story of this class.
• FDA has warned that these products carry the potential for heart attack, stroke, acute liver failure, psychosis and hallucinations, sexual dysfunction, infertility and testicular shrinkage. The liver record specifically includes published cases of severe cholestatic hepatitis in young men with no other risk factors, from product bought online.
• A published analysis of 44 products found only 52% actually contained a SARM, 39% contained a different unapproved drug, 25% contained an unlisted substance, and just 41% matched the labelled amount. What is in the bottle is frequently not what the label says.

Human pharmacology exists only for a couple of these compounds — mainly enobosarm and ligandrol, where suppression of the body's own testosterone is documented and dose-related. For RAD-140, YK-11, S23 and the rest sold under this banner there is no adequate controlled human data, so half-lives and recovery figures repeated online are extrapolation rather than measurement. The claim that SARMs do not suppress is false for the ones that have been studied and unknown for the ones that have not. SARMs are prohibited in tested sport and are a common cause of athlete sanctions, sometimes from contaminated supplements the athlete did not know contained them.

Documented in trials and case reports: dose-dependent natural testosterone suppression, adverse lipid shifts, and a growing case-report literature of drug-induced liver injury. The bigger practical risk: JAMA analyses found most products sold as "SARMs" online are mislabeled — wrong compound, wrong dose, or containing actual steroids. You cannot know what you bought.

• Anyone with existing liver disease or raised liver enzymes
• Anyone with cardiovascular disease or unfavourable lipids
• Anyone trying to conceive, or who wants to preserve fertility
• Anyone competing in tested sport
• Anyone pregnant or breastfeeding
• Adolescents and young adults, who are a particularly vulnerable group — though there is no age at which an unapproved compound with this risk profile becomes safe

• Any hepatotoxic drug or supplement — alcohol, high-dose paracetamol, oral steroids, some bodybuilding supplements — compounds the liver risk.
• Statins and other lipid drugs, because the HDL suppression works against them.
• Anything requiring a stable hormonal picture, including fertility treatment.
• Anti-doping: an automatic sanction in tested sport, including from contaminated supplements.

• Liver enzymes (ALT, AST, bilirubin) — the most important, because drug-induced liver injury is the best-documented serious harm.
• Full lipid panel — HDL suppression is consistent and often marked.
• Total and free testosterone, LH and FSH, which show the degree of suppression.
• Haematocrit.
• Blood pressure.

Whether and how fast natural testosterone production recovers cannot be generalised across these compounds — the one short controlled study followed men only briefly after 21 days of exposure, and most of these chemicals have no human recovery data at all. Some of the lean mass gained is lost as the androgen signal falls away. Liver enzyme elevations usually recover after stopping, but the published cholestatic injury cases took months to resolve and needed medical management. Anyone stopping after a long or high-dose run should get bloodwork rather than assume recovery, and anyone with jaundice, dark urine or right-sided abdominal pain needs to be seen immediately rather than waiting to see if it settles.

US: not approved for human use; sale for consumption is illegal (FDA warning letters are routine), though widely sold as "research chemicals". WADA-banned. Military drug tests screen for them.

Papers about this compound, not proof of the claims above. A title says what was studied, which is sometimes a negative result or a different question entirely.

• Selective Androgen Receptor Modulators (SARMs) Effects on Physical Performance: A Systematic Review of Randomized Control Trials
  Clin Endocrinol (Oxf), 2025
• Selective androgen receptor modulators: a critical appraisal
  Front Endocrinol (Lausanne), 2025

• SarcopeniaJoint Bone Spine · 2019
• Testosterone Replacement Therapy in Hypogonadal MenEndocrinol Metab Clin North Am · 2022
• Current and investigational medications for the treatment of sarcopeniaMetabolism · 2023
• Selective Androgen Receptor Modulators2012
• Sarcopenia and osteoporosisGerontology · 2025
• Selective Androgen Receptor Modulators-Transformative Drugs or Heralds of the Next Drug Epidemic?JAMA · 2024
• Selective androgen receptor modulators: a critical appraisalFront Endocrinol (Lausanne) · 2025
• Development of selective androgen receptor modulators (SARMs)Mol Cell Endocrinol · 2018
• Selective Androgen Receptor Modulators: An Emerging Liver ToxinJ Clin Transl Hepatol · 2023
• The androgen receptorVitam Horm · 2023
• Novel androgen therapies including selective androgen receptor modulatorsBest Pract Res Clin Endocrinol Metab · 2022
• Selective Androgen Receptor Modulators: Current Knowledge and Clinical ApplicationsSex Med Rev · 2019