S23 (Most Potent SARM)
Non-steroidal SARM, the MOST POTENT compound of the SARM class in in vivo AR-binding affinity (Jones 2009 PMID 19299500). Originally investigated as a male contraceptive candidate – REVERSIBLE azoospermia in rat trials (Jones 2010 PMID 20308559). In bodybuilding context FULL HPTA suppression + intense side effects. WADA-banned.
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WHAT IS S23 (MOST POTENT SARM)?
Detailed overview
S23 is a non-steroidal selective androgen receptor modulator (SARM), aryl-propionamide structure. The MOST POTENT compound of the SARM class in in vivo AR-binding affinity – Jones 2009 PMID 19299500 rat bioassay showed ~95% testosterone-level AR activity, higher than RAD-140 (~80%). Originally investigated by the Tennessee University Dalton group as a male hormonal contraceptive candidate (Dalton 2011 PMID 21674508): Jones 2010 PMID 20308559 rat trial showed 100% reversible azoospermia within 4-6 weeks at 1-3 mg/day. Clinical male contraceptive development did not proceed further (financial reasons + safety profile questions). On the bodybuilding market S23 has a 'hard-SARM' reputation (extremely potent muscle builder + strict side effect profile). UGL user reports: drastic lean mass gain (more potent than RAD-140), BUT full HPTA suppression within 4 weeks, intense mood changes (anecdotal 'aggression increase'), hepatotoxicity signs. NO clinical precedent in humans – Phase 0 rat data only. Solomon 2019 PMID 31077635 SARM-DILI review documented 3 S23-associated hepatocellular injury cases (small sample, but at high-dose UGL use). WADA-banned year-round (S1.2). The riskiest SARM class compound for experimenters – NOT recommended for first-SARM users.
Mechanism
Non-steroidal selective AR modulator (aryl-propionamide). MOST POTENT SARM in AR binding affinity.
Anabolic activity (Jones 2009)
~95% testosterone-level in vivo (rat bioassay). Higher than RAD-140.
Half-life
~12 h (oral)
Onset
1-2 weeks
Legal status
Never an Rx (Phase I never started in humans). UGL 'research chemical'. WADA-banned S1.2.
Data console
Lab data
Safety
Side effects, stop signs, contraindications
Side effects · 7
- Complete HPTA suppression and arrest of spermatogenesis: as a strong AR agonist S23 drives LH/FSH suppression via negative feedback; in rats (Jones 2010) 1–3 mg/day caused reversible azoospermia, with fertility recovery taking 3–6 months (no human data).
- Hepatotoxicity (SARM-induced liver injury): hepatocellular / cholestatic DILI cases documented for the SARM class (Cureus, Eur J Clin Pharmacol case reports) apply to S23; ALT/AST/GGT elevation, jaundice and raised bilirubin may occur.
- Severe lipid disturbance: marked HDL cholesterol drop typical of SARMs (up to ~50%), unfavourable LDL/HDL shift, and elevated long-term cardiovascular risk.
- Prostate androgenic effect: S23 is less tissue-selective than other SARMs (Ostarine, S4), with high AR activity in the prostate as well – PSA elevation and prostate stimulation are possible.
- Androgenic skin and hair effects: acne, increased sebum production, and male-pattern hair loss in predisposed individuals.
- Mood and behavioural changes: anecdotal user reports of increased irritability, aggression and sleep disturbance, which may worsen with a psychiatric predisposition.
- Testosterone-suppression symptoms during and after the cycle: reduced libido, fatigue, testicular shrinkage (–40% testis mass in 4 weeks in rats), and low mood with prolonged recovery if no PCT is used.
Contraindications · 7
- Planning fatherhood / conception in the near or mid term: absolutely avoid given S23's strong, documented suppression of spermatogenesis (azoospermia in rats), with fertility recovery taking 3–6 months or longer.
- Pre-existing liver disease or elevated baseline ALT/AST: an absolute contraindication due to SARM-DILI risk.
- Women, especially during or planning pregnancy: the high-potency androgenic AR activity can cause rapid, partly irreversible virilization (voice deepening, hirsutism, clitoral enlargement) and fetal harm.
- Prostate disease, elevated PSA or a history of prostate cancer: contraindicated because of S23's non-selective, high prostate AR activity.
- Cardiovascular disease or dyslipidemia: the marked HDL drop and adverse lipid profile worsen pre-existing risk.
- Psychiatric predisposition (depression, anxiety, aggression/impulse disorders): avoid due to mood side effects and HPTA-suppression-related mood deterioration.
- Concurrent alcohol use, other hepatotoxic agents or stacking with other SARMs/AAS: avoid due to cumulative liver and HPTA burden; also for competitive athletes (WADA-banned year-round, S1.2).
Related Performance Compounds
Same therapeutic category
Studies
Related research and clinical findings
A selective androgen receptor modulator for hormonal male contraception.
Chen J, Hwang DJ, Bohl CE, Miller DD, Dalton JT
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.
Jones A, Chen J, Hwang DJ, Miller DD, Dalton JT
Selective Androgen Receptor Modulators (SARMs)-Induced Liver Injury: A Case Report and Review of Literature.
Mohamed WT, Jahagirdar V, Fatima I, Ahmed MK, Goyal A, Sodeman T, Anwar N
LGD-4033 and a Case of Drug-Induced Liver Injury: Exploring the Clinical Implications of Off-Label Selective Androgen Receptor Modulator Use in Healthy Adults.
Labban H, Kwait B, Paracha A, Khan A, Singh M, Lopez R
Selective androgen receptor modulator use and related adverse events including drug-induced liver injury: Analysis of suspected cases.
Leciejewska N, Jędrejko K, Gómez-Renaud VM, Manríquez-Núñez J, Muszyńska B, Pokrywka A
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The information here is for educational and scientific purposes only. Performance-enhancing compounds (AAS, prohormones, stimulants, doping agents) are illegal without prescription in Hungary and most of the EU, and carry serious health and legal risks. WADA bans them in competitive sport. This is NOT a usage guide, and we do not encourage any illegal use. If you do use them, medical supervision and regular bloodwork are ESSENTIAL. Severe endocrine, cardiovascular, hepatic and psychiatric side effects are possible.