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DPreclinical / mechanistic only
No human data

Andarine

S4 · S-4

Andarine (S4, S-4) is an investigational nonsteroidal arylpropionamide-derived selective androgen receptor modulator (SARM) that was studied preclinically for muscle wasting, osteoporosis and benign prostatic hyperplasia but was never approved for human use and has no published human clinical trial establishing its safety or efficacy. It is sold illicitly as a "research chemical"/muscle-building supplement. The main dangers are: (1) essentially all human safety knowledge is extrapolated from other SARMs and from preclinical rodent/dog data — meaning real-world risk is largely uncharacterized; (2) SARMs as a class have caused serious cholestatic and hepatocellular drug-induced liver injury (jaundice, months-long recovery) in otherwise healthy young users; (3) it suppresses the reproductive hormone axis (shown in animals); (4) illicit products are frequently mislabeled, underdosed, overdosed, or contaminated. A yellowish visual tint and impaired night/dark adaptation are widely reported anecdotally with andarine specifically, but this is not confirmed by any verified primary human study. Anyone using it should treat it as an unapproved drug of unknown human safety, monitor liver function, and involve a clinician.

Clinical readoutSARM · sarm
Hepatic strainHigh
CardiovascularModerate
HPTA suppressionHigh
Half-life
3.3 h
Route
Oral
Evidence
D
Active
Not established in huma…
3.3 h6.7 h10 h13.3 h16.7 h
Illustrative single-compartment washout · each mark = one half-life · t½ ≈ No human data. Preclinical: ~2.6-5.3 h in rats (dose-dependent); ~200 min (~3.3 h) in dogs.
Pharmacology

Mechanism of action

Andarine binds the androgen receptor (AR) with high affinity and acts as a tissue-selective partial agonist. In castrated male rats it restored skeletal muscle mass/strength and bone mineral density (anabolic, full-agonist-like in muscle/bone) while producing only weak agonism in the prostate and seminal vesicles (androgenic-sparing), the defining "tissue-selective" SARM profile. It also acts as an agonist in the pituitary, dose-dependently lowering LH and FSH. Its arylpropionamide structure contains a nitro-aromatic (A-ring) chromophore, the feature hypothesized (mechanistically, not proven in humans) to underlie the reported visual/color-perception effects.
Kinetics

Pharmacokinetics

Half-life

No human data. Preclinical: ~2.6-5.3 h in rats (dose-dependent); ~200 min (~3.3 h) in dogs.

Active duration

Not established in humans. Rodent/canine kinetics and anti-doping urinary detection windows suggest a short-to-moderate systemic duration (roughly daily dosing in illicit use), but no validated human active-duration data exist.

Route

Oral (orally bioavailable arylpropionamide); high oral bioavailability shown preclinically (e.g., ~91% in dogs at pharmacologic doses, dose-dependent).

Metabolism & clearance

Extensively hepatically metabolized via phase I and phase II pathways — amide-bond hydrolysis, deacetylation of the B-ring, reduction of the A-ring nitro group, hydroxylation, then glucuronide/sulfate conjugation; eliminated largely as metabolites. Human urinary phase I/II metabolites have been characterized for anti-doping purposes. Note: PK/metabolite information here is for clinical monitoring and washout understanding, not to evade drug testing.

For monitoring and washout planning, not drug-test evasion.

Reported effects

Physiological & performance effects

  • Preclinical (rodent): increased skeletal muscle mass and contractile strength; restored castration-induced loss of lean body mass
  • Preclinical (rodent): increased/maintained bone mineral density and bone strength; reduced body fat
  • Weak agonist activity in prostate/seminal vesicle relative to muscle (tissue selectivity) in animals
  • Suppression of pituitary gonadotropins (LH, FSH) in animals
  • No verified human efficacy data exist — human anabolic/performance effects claimed by users are not established by primary human trials
  • Commonly reported anecdotally (not verified in primary human literature): yellow/green visual tint and difficulty adapting to low light/darkness
Safety

Adverse effects by system

Cardiovascular

No adequate human data specific to andarine. SARMs as a class raise concern for adverse lipid changes (notably HDL-cholesterol lowering) and cardiovascular events; case reports of SARM users describe cardiovascular complications. Andarine-specific cardiovascular risk is uncharacterized — treat as unknown/potentially harmful.

Hepatic

No andarine-specific human case report was identified, but multiple SARMs (RAD-140, LGD-4033, ostarine/enobosarm, stenabolic) have caused clinically significant drug-induced liver injury (cholestatic and hepatocellular, with jaundice, pruritus, marked bilirubin/enzyme elevations) in previously healthy young users. Because andarine is a structurally related SARM eliminated by extensive hepatic metabolism, hepatotoxicity must be assumed possible until human safety data exist.

Endocrine / HPTA

Suppression of LH and FSH shown dose-dependently in animals, implying likely suppression of endogenous testosterone/reproductive-hormone production in humans. No verified human HPTA data for andarine specifically; class evidence (other SARMs) confirms testosterone suppression is expected.

Reproductive

Gonadotropin (LH/FSH) suppression in animals implies potential impairment of spermatogenesis/fertility and testosterone production. No verified human reproductive-outcome data for andarine.

Neuropsychiatric

No adequate human data specific to andarine. Class case reports of SARM users have noted mood/psychiatric disturbances; andarine-specific neuropsychiatric risk is unknown.

Renal

No adequate human or preclinical data specifically implicating renal toxicity for andarine. Renal effects are essentially uncharacterized — absence of data is not evidence of safety.

Hematologic

No adequate human data specific to andarine. Androgenic compounds can raise hematocrit/erythrocytosis; SARMs are generally reported to do so less than anabolic steroids, but andarine-specific hematologic effects are uncharacterized.

Dermatologic

No adequate human data specific to andarine. Cholestatic liver injury from SARMs can cause pruritus and jaundice (skin/scleral yellowing) secondarily. Direct dermatologic effects of andarine are uncharacterized.

Recovery

HPTA suppression & recovery

Suppression: Expected/moderate-to-significant based on preclinical gonadotropin suppression; not quantified in humans

Andarine dose-dependently lowered LH and FSH in animal studies, so meaningful suppression of the hypothalamic-pituitary-testicular axis and endogenous testosterone should be assumed in humans, though human recovery kinetics are not characterized. Recovery, if suppression occurs, is expected to occur gradually after discontinuation, but this is unproven for andarine. Any post-use hormonal management should be individualized and directed by an endocrinologist with biochemical (blood) confirmation. This monograph does not endorse self-managed hormonal 'recovery' protocols; if a SERM is ever considered for suppression it must be a single agent under physician supervision — never a dual-SERM regimen.

Bloodwork & vitals

Monitoring

Recommended labs & checks
Liver function panel (ALT, AST, ALP, total and direct bilirubin, GGT) at baseline and periodicallyTotal testosterone, LH, FSH (and estradiol) to assess HPTA suppressionFasting lipid panel (total, LDL, HDL, triglycerides)Complete blood count including hematocrit/hemoglobinRenal function (creatinine, eGFR) as general safety baseline

Cadence: Baseline before any use; recheck liver function and hormones within roughly 4-8 weeks and promptly if any symptoms arise; and after discontinuation to confirm recovery. Because andarine is unapproved with no established human safety monitoring schedule, err toward more frequent clinician-directed testing.

Warning signs — seek care
  • Jaundice (yellow skin/eyes), dark urine, pale stools, itching — stop immediately and seek urgent care (possible liver injury)
  • Right-upper-quadrant or diffuse abdominal pain, nausea, vomiting, unusual fatigue
  • New visual disturbance (yellow/green tint, poor night vision) — reported anecdotally with andarine
  • Chest pain, palpitations, breathlessness, or edema
  • Reduced libido, erectile dysfunction, testicular shrinkage, mood changes (suggesting hormonal suppression)
Do not use if

Contraindications

  • Pre-existing or active liver disease, or any unexplained elevation of liver enzymes/bilirubin
  • Concurrent use of other hepatotoxic drugs, anabolic-androgenic steroids, or other SARMs
  • Pregnancy, possible pregnancy, or breastfeeding (androgenic teratogenic potential; no safety data)
  • Adolescents/those not skeletally mature (androgen exposure risks)
  • Known or suspected androgen-sensitive malignancy (e.g., prostate cancer) without oncology oversight
  • Pre-existing cardiovascular disease or adverse lipid profile
  • Desire to preserve fertility/testosterone without endocrinologic monitoring
  • Any use without access to clinical monitoring — given its unapproved status and unknown human safety
Combinations

Interaction profile

  • ModerateWith a thermogenic stimulant: Additive cardiovascular strain
  • ModerateWith an anabolic steroid: Hormonal
  • ContraindicatedWith DNP: Additive cardiovascular strain

Check a specific combination in the interaction checker.

Harm reduction

Reducing harm & when to stop

  • Recognize this is an unapproved investigational drug with no human safety trial — its human risk profile is genuinely unknown, not merely 'mild'.
  • Do not combine andarine with alcohol, other hepatotoxic drugs, anabolic-androgenic steroids, or other SARMs — layering hepatotoxic and androgenic agents compounds liver and hormonal risk.
  • Get baseline bloodwork (liver panel, lipids, testosterone/LH/FSH, CBC) before use and repeat during and after; involve a clinician even if you do not disclose intent to use, framing it as monitoring.
  • Stop immediately and seek urgent medical care for any jaundice, dark urine, pale stools, itching, right-upper-quadrant pain, or persistent nausea/fatigue — these can signal liver injury that occasionally progresses.
  • Stop and see a clinician for new visual changes (yellow tint, poor night vision), chest pain/palpitations, or signs of hormonal suppression (low libido, erectile dysfunction, testicular shrinkage, mood change).
  • Illicitly sold SARM products are frequently mislabeled, mis-dosed, or contaminated; the actual contents and dose you ingest are uncertain.
  • Any concern about hormonal suppression or 'recovery' should be evaluated by an endocrinologist with blood tests — do not self-manage with SERMs, and never use dual-SERM regimens.
  • There is no established 'safe' dose: doses reported in illicit use are not validated by human safety data and carry the risks above.
Evidence

Citations (12)

Every clinical claim above is tied to a primary source. Overall evidence grade D — this compound lacks adequate human data; claims rest on preclinical or mechanistic evidence.

  1. 01

    Andarine (S-4) is a nonsteroidal arylpropionamide SARM that in castrated rats restored muscle mass/strength and bone mineral density with only weak prostate agonism (tissue selectivity), and dose-dependently decreased plasma LH and FSH via pituitary agonism.

    PreclinicalSelective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats.PMID 16099859 ↗

  2. 02

    S-4 prevented bone loss (maintained whole-body and trabecular BMD, increased bone strength) and reduced body fat in ovariectomized rats.

    PreclinicalSelective Androgen Receptor Modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats.PMID 17063395 ↗

  3. 03

    In rats, S-4 is rapidly absorbed, slowly cleared, with a half-life of ~2.6-5.3 h and dose-dependent (up to complete) oral bioavailability.

    PreclinicalPharmacokinetics of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide in rats, a non-steroidal selective androgen receptor modulator.PMID 15204699 ↗

  4. 04

    In dogs S-4 showed a half-life of ~200 min and ~91% oral bioavailability at pharmacologic doses, and is eliminated largely by hepatic metabolism via phase I and phase II enzymes (deacetylation, nitro reduction, amide hydrolysis, oxidation, conjugation).

    PreclinicalIn vivo metabolism and final disposition of a novel nonsteroidal androgen in rats and dogs.PMID 16815963 ↗

  5. 05

    Human urinary phase I and II metabolites of andarine (glucuronide/sulfate conjugates, monohydroxylated/deacetylated and B-ring-cleaved products) have been characterized, confirming human hepatic metabolism and providing washout/monitoring context.

    PreclinicalMass spectrometric characterization of urinary metabolites of the selective androgen receptor modulator andarine (S-4) for routine doping control purposes.PMID 20623476 ↗

  6. 06

    Andarine (S-4) has been detected in human athlete doping-control samples, confirming real-world human use/misuse despite lack of clinical approval.

    Case reportSARM-S4 and metabolites detection in sports drug testing: a case report.PMID 21816554 ↗

  7. 07

    Andarine (S-4) was identified in a human doping-control sample, further documenting human exposure.

    Case reportDetection of the selective androgen receptor modulator S-4 (Andarine) in a doping control sample.PMID 23427117 ↗

  8. 08

    SARMs as a class have caused serious drug-induced liver injury (cholestatic/hepatocellular, with jaundice and prolonged recovery) in previously healthy young users; illustrative published SARM DILI cases and review.

    Case seriesSelective Androgen Receptor Modulators (SARMs)-Induced Liver Injury: A Case Report and Review of LiteraturePMID 36945289 ↗

  9. 09

    SARM use produced hepatotoxicity with jaundice and elevated liver enzymes that resolved on discontinuation, underscoring class hepatotoxic risk.

    Case reportSelective Androgen Receptor Modulator Induced Hepatotoxicity.PMID 35340496 ↗

  10. 10

    Enobosarm (ostarine), a related SARM, caused hepatocellular drug-induced liver injury in a healthy young man, demonstrating SARM-class hepatotoxicity relevant by extrapolation to andarine.

    Case reportDrug-Induced Liver Injury Secondary to Enobosarm: A Selective Androgen Receptor Modulator.PMID 35655632 ↗

  11. 11

    Off-label SARM (LGD-4033) use in a healthy adult caused drug-induced liver injury, and SARMs as a class are associated with hepatotoxicity, cardiovascular complications, endocrine disturbances, and psychiatric symptoms.

    Case reportLGD-4033 and a Case of Drug-Induced Liver Injury: Exploring the Clinical Implications of Off-Label Selective Androgen Receptor Modulator Use in Healthy Adults.PMID 39421081 ↗

  12. 12

    S4/andarine has been studied only preclinically (in vitro/animal) and has no completed published human clinical trial; it is used illicitly as a bodybuilding supplement with favorable oral bioavailability.

    PreclinicalExploring the potentials of S4, a selective androgen receptor modulator, in glioblastoma multiforme therapy.PMID 38997069 ↗

Last reviewed 2026-07-06 · Verified against PubMed · Educational, not medical advice