NOT FOR HUMAN CONSUMPTION

S4 (Andarine, GTx-007) is a nonsteroidal selective androgen receptor modulator (SARM) developed by GTx for osteoporosis, muscle wasting, and benign prostatic hyperplasia (BPH). It binds the androgen receptor (AR) with tissue-selective, partial agonist activity—aiming to stimulate bone and muscle while sparing prostate and hair follicles relative to testosterone/DHT. Clinical development never reached approval; most human data are early-phase. It is not approved for any indication and is prohibited by WADA.

Additional Benefits of S-4 Now Under Investigation

2. Molecular Mechanism of Action

2.1 Receptor pharmacodynamics

• Target: Andarine binds the androgen receptor (AR) as a partial agonist with a distinct co-activator recruitment profile compared to DHT/testosterone.

• Tissue selectivity:

  • Skeletal muscle & bone: Acts more like an agonist, promoting protein synthesis, antiresorptive signaling, and osteoblastic activity.

  • Prostate & reproductive tissues: Behaves less strongly than DHT; in some models, functions almost as a functional antagonist by competing with endogenous androgens.

2.2 Down-stream biology

3. Pharmacokinetics (from early studies & preclinical data)

• Route: Oral, typically once or twice daily in trials.

• Half-life: On the order of hours (short–moderate); supports BID dosing in many experimental protocols.

• Absorption: Good oral bioavailability; lipophilic.

• Distribution: Binds AR in muscle, bone, prostate, and other AR-rich tissues; crosses into many organs.

• Metabolism: Hepatic metabolic clearance; exact CYP profile not publicly characterized.

• Excretion: Primarily renal and biliary as metabolites.

4. Pre-clinical & Clinical Evidence

• Osteoporosis/Bone models: S-4 restored BMD and bone strength in ovariectomized rats while keeping prostate size relatively low compared with DHT.

• Muscle wasting/hypogonadism models: Improved lean mass and strength, outperforming placebo and approaching low-dose testosterone’s anabolic effect with less androgenic tissue impact.

• BPH/androgen-deprivation settings: Showed ability to maintain muscle/bone under androgen deprivation while not excessively stimulating prostate, making it attractive in theory as an adjunct to androgen-deprivation therapy.

Evidence quality note: Most data are animal studies plus small, early-phase human trials. There are no large Phase 3 data, no approved indications, and the full risk–benefit profile at therapeutic doses remains incompletely defined.

5. Emerging Clinical Interests (conceptual)

6. Safety and Tolerability

Important: Much of the human safety profile is inferred from limited trial data and off-label/grey-market use, not long, high-quality RCTs.

6.1 Commonly reported / expected

• Visual disturbances (hallmark of S-4):

  • Yellow tint to vision or altered color perception.

  • Night-vision difficulty (reduced adaptation in low light).

  • Usually dose-related and reversible after discontinuation in reports; likely due to S-4 or its metabolites affecting retinal signaling (exact mechanism uncertain).

• Endocrine suppression:

  • Decreased LH/FSH, total and free testosterone with prolonged exposure.

  • Potential testicular atrophy and transient subfertility with chronic use.

• Androgenic/skin: Mild acne, oily skin, hair shedding in susceptible individuals—generally milder than full androgenic steroids at equivalent anabolic effect.

• Lipids: HDL reduction and possible LDL increase, as with many androgens/SARMs.

• Liver: Mild ALT/AST elevations reported anecdotally; robust hepatotoxicity data are lacking but caution is appropriate.

6.2 Less common / theoretical

• Cardiometabolic: Possible BP increases, hematocrit drift, and unknown long-term cardiovascular risk.

• Mood/neurologic: Some users report irritability, decreased libido with endogenous suppression; data are anecdotal.

• Reproductive: Potential impact on spermatogenesis and fertility with long-term use; recovery time after cessation is not well characterized.

• Oncology: Long-term tumor risk with chronic partial AR stimulation/inhibition has not been mapped; caution in anyone with a history of hormone-sensitive cancers.

6.3 Anti-doping / legal status

• WADA: SARMs (including S-4/Andarine) are prohibited at all times (S1.2 anabolic agents).

• Regulation: S-4 is not an approved medication; many jurisdictions treat SARMs sold for human consumption as unlawful or controlled. Grey-market powders/capsules often have mislabeling and contamination.

7. Comparative Snapshot (SARMs & anabolics)

8. Regulatory Landscape

• No approvals in US/EU/UK/most jurisdictions.

• Used only in research; any therapeutic development has stalled in favor of newer SARMs or different anabolic approaches.

• Widely sold online as a research chemical, often in non-GMP conditions with unverified purity and dose.

9. Practical Take & Future Directions

• For now: S-4 is best regarded as a historical SARM prototype and research tool, not a clinical therapy.

• Main unique point: Its bone-/muscle-anabolic + prostate-sparing profile and distinct visual side effects make it mechanistically interesting but clinically problematic.

• Research priorities:

  • Detailed characterization of the ocular mechanism and long-term retinal safety.

  • Development of next-generation SARMs that retain S-4’s bone/muscle selectivity without vision issues.

  • More complete mapping of lipid, cardiovascular, and reproductive impacts of AR partial agonism vs full agonism.