S4 (Andarine, GTx‑007)
Non-steroidal SARM (Andarine, GTx-007), GTx Inc 2005. UNIQUE side effect: dose-dependent YELLOW VISION and night blindness (Marhefka 2004 PMID 15267281 – retinal opsin binding). On the bodybuilding market a 'fat-loss + cutting' SARM reputation. WADA-banned.
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WHAT IS S4 (ANDARINE, GTX-007)?
Detailed overview
S4 (Andarine, GTx-007) is a non-steroidal selective androgen receptor modulator (SARM) developed by GTx Inc in 2005 (Gao 2005 PMID 16270235 in vivo characterization). Structurally an aryl-propionamide derivative (NOT a steroid), AR-binding affinity ~70% of testosterone level in vitro (Kim 2005 PMID 16080187). **Unique side effect**: Marhefka 2004 PMID 15267281 showed that the S4 molecule also binds to retinal opsins (photon-sensing pigments) – dose-dependent SIDE EFFECTS: (1) **yellow vision** (yellow tint vision), classically with yellowish-green color emphasis, blue dulling; (2) **night blindness** at high doses. Both effects are REVERSIBLE within 4-6 weeks of stopping S4. Clinical development: Phase I 2007, Phase II 2008-2010 for BPH (benign prostatic hyperplasia) + cachexia indications – Phase II results were below moderate clinical-meaningfulness. After 2010 GTx focused clinical development on Ostarine, S4 deprioritized. On the bodybuilding market a 'fat-loss + cutting SARM' reputation (anecdotal low water retention + relatively moderate HPTA suppression + the vision side effect as 'unique' identifier). Hepatotoxicity risk lower than RAD/LGD (shorter half-life → reactive metabolite clearance faster), but NOT zero. WADA-banned year-round (S1.2).
Mechanism
Non-steroidal selective AR modulator + UNIQUE retinal opsin binding (visual side effect)
Anabolic activity (Gao 2005)
In rat bioassay anabolic activity ~60-70% Test-level (in vivo)
Half-life
~4 h (oral, SHORT – requires 2-3x daily dosing)
Onset
1-2 weeks
Legal status
Never an Rx (GTx deprioritized after Phase II in 2010). UGL 'research chemical'. WADA-banned S1.2.
Data console
Lab data
Safety
Side effects, stop signs, contraindications
Side effects · 7
- Dose-dependent yellow tint vision: blue-light perception dulls and the color palette shifts toward yellow-green. Reported by roughly 30% of users at 50+ mg/day (retinal opsin binding, Marhefka 2004).
- Night blindness at high doses (>75 mg/day) in roughly 10-20% of users, due to rod-opsin involvement and reduced low-light vision. Reversible within 4-6 weeks after discontinuation.
- HPTA suppression (lowered endogenous testosterone, LH/FSH): milder than with LGD-4033 or RAD-140 because of the short (~4 h) half-life, but not zero, PCT is usually needed.
- Adverse lipid shift: drop in HDL cholesterol, typical of the SARM class. Lipid disturbance is moderate on S4 but should be monitored.
- Hepatotoxicity (liver injury): moderate, milder than with RAD/LGD due to faster reactive-metabolite clearance from the short half-life, but not zero, SARM-associated drug-induced liver injury (DILI) is documented with S4 too.
- Virilization in women at higher doses: voice deepening, increased hair growth, acne, menstrual disruption. Some androgenic effects (e.g. voice changes) can be permanent.
- Compliance and daily-fluctuation risk: the short (~4 h) half-life requires 2-3 doses per day, missed doses cause unstable effect and unpredictable onset of side effects.
Contraindications · 7
- Pre-existing eye disease or visual disorder (glaucoma, retinopathy, retinal/opsin involvement): absolute contraindication because of S4's retinal opsin-binding visual side effect.
- Occupations where night vision is critical (driver, pilot, machine operator): the risk of night blindness and yellow vision creates an accident hazard.
- Pregnancy and breastfeeding: androgenic activity can cause fetal virilization, absolutely to be avoided.
- Planned fatherhood or existing subfertility: HPTA suppression transiently impairs spermatogenesis, recovery can take 2-3 months.
- Pre-existing liver disease or elevated liver enzymes: increases the risk of SARM-associated hepatotoxicity.
- Competitive sport under WADA rules: S4 is banned year-round (S1.2), detectable in urine for 1-2 weeks, the faster clearance offers no hiding place.
- Dyslipidemia or cardiovascular risk: the HDL drop worsens the lipid profile, increased monitoring or avoidance is warranted.
Related Performance Compounds
Same therapeutic category
Studies
Related research and clinical findings
Pharmacokinetics 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.
Kearbey JD, Wu D, Gao W, Miller DD, Dalton JT
The para substituent of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamides is a major structural determinant of in vivo disposition and activity of selective androgen receptor modulators.
Kim J, Wu D, Hwang DJ, Miller DD, Dalton JT
Design, synthesis, and biological characterization of metabolically stable selective androgen receptor modulators.
Marhefka CA, Gao W, Chung K, Bell W, Wu D, Yang HM, Joseph JT, Bohl C, Mustafa S, 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
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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.