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DPreclinical / mechanistic only
High riskNo human data

S-23

S-23 is a nonsteroidal, arylpropionamide-class selective androgen receptor modulator (SARM) that acts as a full agonist at the androgen receptor. It has never been tested in humans for safety or efficacy: the entire body of pharmacology comes from rodent studies where it was developed as a candidate male hormonal contraceptive (combined with estradiol), plus human "microdose" pharmacokinetic work done only to build anti-doping detection assays. No SARM, including S-23, is approved for human use anywhere; it circulates only as an unapproved research chemical and as an adulterant in bodybuilding "supplements," and it is a banned substance in sport. Because there is essentially no human safety data, its risks are inferred from the SARM class, which has caused severe drug-induced liver injury (including cholestasis with bilirubin >40 mg/dL and secondary bile-cast kidney injury), suppression of the hypothalamic-pituitary-testicular axis, and in rats profound, dose-dependent suppression of sperm production. Anyone using it is effectively self-experimenting with an uncharacterized drug with no human safety data.

Clinical readoutSARM · sarm
Hepatic strainVery high
CardiovascularNone
HPTA suppressionHigh
Half-life
Not formally char…
Route
Oral
Evidence
D
Active
Unknown in humans
1·t½2·t½3·t½4·t½5·t½
Illustrative single-compartment washout · each mark = one half-life · t½ ≈ Not formally characterized in humans. It is orally active. In an anti-doping microdose study, the parent drug and metabolites were detectable for long periods (a single 1 microgram oral dose detectable ~253 h and a 50 microgram dose ~544 h on average in urine), and in horses parent S-23 was detectable in plasma up to ~143 h, implying a relatively long terminal elimination of drug/metabolites; a true plasma half-life has not been established.
Pharmacology

Mechanism of action

S-23 binds the androgen receptor (AR) with high affinity (inhibitory constant Ki ≈ 1.7 nM in vitro) and behaves as a full AR agonist in both androgenic and anabolic tissues, unlike more tissue-selective SARMs that spare the prostate. AR activation in muscle and bone drives anabolic signaling (increased lean mass and bone mineral density in rats), while AR/androgen negative feedback at the hypothalamus and pituitary suppresses gonadotropin (LH and FSH) secretion, which in turn lowers intratesticular testosterone and shuts down spermatogenesis. Being nonsteroidal and non-aromatizable, it is not converted to estrogen, so in rat contraceptive models exogenous estradiol had to be co-administered to maintain sexual behavior. All of this mechanistic understanding is preclinical/mechanistic; the human dose-response relationship is uncharacterized.
Kinetics

Pharmacokinetics

Half-life

Not formally characterized in humans. It is orally active. In an anti-doping microdose study, the parent drug and metabolites were detectable for long periods (a single 1 microgram oral dose detectable ~253 h and a 50 microgram dose ~544 h on average in urine), and in horses parent S-23 was detectable in plasma up to ~143 h, implying a relatively long terminal elimination of drug/metabolites; a true plasma half-life has not been established.

Active duration

Unknown in humans; rat contraceptive dosing was once daily, consistent with oral daily activity, but duration of pharmacodynamic effect in humans is uncharacterized.

Route

Oral (as studied); illicit products are typically oral liquids or capsules.

Metabolism & clearance

Hepatic metabolism predominates: phase I hydroxylation (mono- and bis-hydroxylation) and B-ring cleavage, followed by phase II glucuronidation and sulfation, with renal excretion of conjugated metabolites. This information is provided for understanding washout and monitoring windows, not for evading drug testing.

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

Reported effects

Physiological & performance effects

  • Full androgen-receptor agonist activity in both muscle/bone (anabolic) and prostate (androgenic) tissues in rats
  • Dose-dependent increase in lean body mass and bone mineral density with reduced fat mass in rats
  • Suppression of luteinizing hormone (LH) and, with prolonged dosing, follicle-stimulating hormone (FSH) in rats
  • Dose-dependent suppression of spermatogenesis (azoospermia in most animals) in the rat contraceptive model, reversible after prolonged washout
  • No demonstrated therapeutic benefit or performance effect established in any human study — human effects are unknown
Safety

Adverse effects by system

Cardiovascular

No human cardiovascular safety data exist for S-23. Androgens and SARMs as a class can adversely affect lipids (notably lowering HDL cholesterol); a SARM used in humans (enobosarm) was studied in a randomized oncology trial, but no cardiovascular outcome data exist for S-23 specifically. Cardiovascular risk should be assumed unquantified and potentially significant.

Hepatic

No S-23-specific human hepatotoxicity reports, but SARMs as a class have caused serious drug-induced liver injury (cholestatic and hepatocellular patterns, with marked hyperbilirubinemia) in case reports involving RAD-140 and enobosarm. S-23 is extensively hepatically metabolized, and class risk should be assumed until human data exist.

Endocrine / HPTA

In rats, S-23 suppressed LH by >50% and, with prolonged dosing, suppressed FSH, indicating strong hypothalamic-pituitary-testicular (HPTA) suppression. In humans this is expected but uncharacterized; endogenous testosterone suppression should be anticipated.

Reproductive

In male rats, S-23 caused dose-dependent suppression of spermatogenesis (no sperm in the testis in most treated animals) and infertility, which was fully reversible after ~100 days of washout in that model. Human reproductive effects are unstudied; temporary or theoretically prolonged fertility impairment cannot be excluded.

Neuropsychiatric

No human or animal psychiatric/neurobehavioral data specific to S-23. Androgenic compounds can be associated with mood changes, irritability, or aggression, but there is no adequate evidence for S-23; effects are unknown.

Renal

No direct S-23 renal data. Acute kidney injury (bile-cast nephropathy) has been reported secondary to SARM-associated liver injury in a multi-SARM user, so severe hepatic injury can drive secondary renal failure.

Hematologic

No S-23-specific human hematologic data. Androgens can raise hematocrit/erythrocytosis; whether S-23 does so in humans is unknown and unmeasured.

Dermatologic

No S-23-specific data. Androgen-receptor agonism can plausibly cause acne, oily skin, or accelerated hair loss in predisposed individuals, but this has not been documented for S-23; effects are unknown.

Recovery

HPTA suppression & recovery

Suppression: Expected to be significant (strong suppression demonstrated in rats; unquantified in humans)

In the rat contraceptive model, S-23 (with estradiol) suppressed LH and FSH and abolished spermatogenesis, with full fertility recovery after roughly 100 days off drug. Human recovery kinetics are unknown. Because S-23 is a non-aromatizable full AR agonist, meaningful HPTA/testosterone suppression should be anticipated. Any suppression or symptomatic hypogonadism after use should be evaluated and managed by an endocrinologist with formal biochemical testing over time; do not attempt self-directed hormonal 'recovery' protocols. Post-cycle pharmacologic intervention is outside evidence for S-23 and, if considered at all, is a physician-directed, single-agent decision made with an endocrinologist — never a self-managed multi-drug regimen.

Bloodwork & vitals

Monitoring

Recommended labs & checks
Liver function panel (ALT, AST, ALP, total and direct bilirubin, GGT) at baseline and periodicallyTotal and free testosterone, LH, FSH (to detect HPTA suppression)Fasting lipid panel (total, LDL, HDL, triglycerides)Complete blood count with hematocrit/hemoglobinRenal function (creatinine, eGFR), especially if any signs of liver injury

Cadence: Baseline before any exposure, then early (e.g., 2-4 weeks) and periodically during use, and again after discontinuation until liver enzymes, lipids, and gonadotropins/testosterone normalize; more frequently at any sign of toxicity. All monitoring should be done with a clinician.

Warning signs — seek care
  • Jaundice, scleral icterus, dark urine, pale stools, or itching (possible cholestatic liver injury) — stop and seek urgent medical care
  • Right-upper-quadrant or diffuse abdominal pain, nausea, anorexia
  • Reduced urine output or swelling (possible kidney involvement)
  • Marked fatigue, weakness, or malaise
  • Testicular shrinkage, low libido, erectile dysfunction, or other signs of hormonal suppression
  • Chest pain, palpitations, or unusual shortness of breath
Do not use if

Contraindications

  • No human safety threshold has ever been established — S-23 is not approved for human use and cannot be considered safe at any dose
  • Pre-existing or active liver disease, or any unexplained transaminase/bilirubin elevation
  • Any interest in preserving fertility or planning conception (rat data show spermatogenesis suppression)
  • Pregnancy, possibility of pregnancy, or breastfeeding (androgenic; no data, potential fetal harm)
  • Cardiovascular disease or adverse lipid profile, given unquantified cardiovascular/lipid risk
  • Concurrent hepatotoxic drugs, anabolic-androgenic steroids, or other SARMs
  • Competitive athletes subject to anti-doping testing (prohibited substance)
  • Adolescents/anyone not skeletally or endocrinologically mature
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

  • Understand that S-23 has no human safety data — using it is self-experimentation with an uncharacterized, unapproved drug; the most protective choice is not to use it.
  • If used despite the risks, get baseline bloodwork (liver panel, lipids, testosterone/LH/FSH, CBC, renal function) and repeat during and after use, working with a clinician; be honest with your provider about what you took.
  • Stop immediately and seek urgent medical care for any sign of liver injury — jaundice, dark urine, pale stools, itching, right-upper-quadrant/abdominal pain, nausea, or profound fatigue.
  • Do not combine with alcohol, other hepatotoxic drugs, anabolic-androgenic steroids, or other SARMs, which compounds liver and hormonal risk.
  • Illicit SARM products are frequently mislabeled, underdosed, overdosed, or contaminated with other compounds; the actual contents are unknown.
  • Expect hormonal (HPTA) suppression; any post-use symptoms of low testosterone should be evaluated and managed by an endocrinologist with objective testing over time, not with self-directed protocols.
  • If fertility matters to you, be aware rat data show sperm suppression; discuss fertility preservation and testing with a physician.
  • This compound is prohibited in sport and will trigger anti-doping violations.
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

    S-23 is a nonsteroidal arylpropionamide SARM that binds the androgen receptor with high affinity (Ki ~1.7 nM) and acts as a full agonist in androgenic and anabolic tissues.

    PreclinicalPreclinical 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.PMID 18772237 ↗

  2. 02

    In rats, S-23 suppressed LH by >50% at doses >0.1 mg/day, and with prolonged co-administration with estradiol suppressed LH and FSH and abolished spermatogenesis (azoospermia in most animals) with zero pregnancies; infertility was fully reversible after ~100 days of washout.

    PreclinicalPreclinical 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.PMID 18772237 ↗

  3. 03

    S-23 increased bone mineral density and lean mass and reduced fat mass in a dose-dependent manner in rats; castrated-rat ED50 was 0.43 mg/day (prostate) and 0.079 mg/day (levator ani muscle).

    PreclinicalPreclinical 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.PMID 18772237 ↗

  4. 04

    S-23 displays full agonist activity in both androgenic and anabolic tissues (less prostate-sparing than other SARMs), with AR binding characterized in vitro.

    PreclinicalNonsteroidal selective androgen receptor modulators enhance female sexual motivation.DOI 10.1124/jpet.110.168880 ↗

  5. 05

    S-23 undergoes hepatic phase I (hydroxylation, B-ring cleavage) and phase II (glucuronidation/sulfation) metabolism.

    PreclinicalCharacterization of in vitro generated metabolites of the selective androgen receptor modulators S-22 and S-23 and in vivo comparison to post-administration canine urine specimens.DOI 10.1002/dta.211 ↗

  6. 06

    Human microdose administration of S-23 (anti-doping study) showed long detection windows (single 1 microgram dose detectable ~253 h, 50 microgram dose ~544 h on average in urine) with 18 metabolites; S-23 has been identified in human doping cases and in contaminated supplements.

    CohortInvestigations Into the Urinary Metabolite Elimination Profile of the Selective Androgen Receptor Modulator S-23 in Studies Mimicking Contaminated Product Ingestion for Doping Control Purposes.DOI 10.1002/bmc.70090 ↗

  7. 07

    S-23 and metabolites were detectable in equine plasma up to ~143 h after oral administration, supporting relatively slow elimination; S-23 is not available as an approved therapeutic and is sold via uncontrolled online sources.

    PreclinicalDetection of the selective androgen receptor modulator S-23 and its metabolites in equine urine and plasma following oral administration.DOI 10.1002/dta.3758 ↗

  8. 08

    No SARM (including S-23) is approved for human consumption; S-23 has been quantified as an ingredient in illicit capsule products.

    ReviewA screening method for the quantitative determination of selective androgen receptor modulators (SARMs) in capsules by high resolution 19F- and 1H-NMR spectroscopy.DOI 10.1039/d4ay00188e ↗

  9. 09

    SARMs as a class have caused severe drug-induced liver injury; a multi-SARM user developed acute liver injury (total bilirubin 43.3 mg/dL) with secondary bile-cast nephropathy (creatinine 4.8 mg/dL) that improved after cessation and plasmapheresis.

    Case reportBile Cast Nephropathy Because of Acute Liver Injury Associated With Selective Androgen Receptor Modulators.DOI 10.14309/crj.0000000000001105 ↗

  10. 10

    RAD-140 (a SARM) caused cholestatic drug-induced liver injury with peak total bilirubin 38.5 mg/dL, biopsy-confirmed, resolving after discontinuation.

    Case reportRAD-140 Drug-Induced Liver Injury.DOI 10.31486/toj.22.0005 ↗

  11. 11

    Enobosarm (a SARM) caused hepatocellular drug-induced liver injury from an over-the-counter muscle-building supplement, resolving after discontinuation.

    Case reportDrug-Induced Liver Injury Secondary to Enobosarm: A Selective Androgen Receptor Modulator.DOI 10.14740/jmc3937 ↗

  12. 12

    A SARM (enobosarm) has been studied in humans in a randomized, double-blind, placebo-controlled phase 2 trial (cancer cachexia), demonstrating that SARMs can be administered to humans in controlled research settings, though no such human trials exist for S-23.

    RCTEffects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial.DOI 10.1016/S1470-2045(13)70055-X ↗

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