What Is Andarine (S4)?
Andarine (S4, GTx-007, S-40503) is a non-steroidal SARM developed by GTx, Inc. alongside Ostarine (MK-2866). While Ostarine advanced to clinical trials, Andarine's preclinical development focused on its particularly strong bone selectivity, and it was not advanced to human trials.
Andarine has high AR binding affinity (Ki ~3.5 nM) and is notable in preclinical research for its ability to preserve bone mineral density in ovariectomized rodent models while simultaneously maintaining muscle mass — a dual anabolic effect on both tissues that estrogen alone does not achieve.
Bone Density Research (OVX Rat Model)
The ovariectomized (OVX) rat is the standard preclinical model for postmenopausal osteoporosis. Key published Andarine data from Gao et al. (2004, Endocrinology):
- OVX rats treated with Andarine 3 mg/kg/day maintained bone mineral density comparable to sham-operated controls
- Femoral BMD and trabecular bone microarchitecture were preserved vs untreated OVX controls
- Andarine was as effective as estrogen for bone density preservation
- Critically: Andarine also maintained levator ani muscle mass (anabolic) — estrogen had no significant muscle effect
- Prostate weight in male rats: minimal increase at bone-protective doses, confirming selectivity
Selectivity Profile
| Tissue | Andarine Effect | vs Testosterone |
|---|---|---|
| Bone (OVX model) | Strong preservation — comparable to estrogen | Testosterone also effective but with prostate effects |
| Skeletal muscle | Maintained levator ani mass | Full agonism |
| Prostate | Minimal stimulation at bone-protective doses | Strong stimulation (DHT-amplified) |
| LH/FSH suppression | Yes (dose-dependent) | Yes |
| Erythropoiesis | Less than testosterone | Elevated Hct |
Visual Side Effect Note (Research Context)
Andarine has a documented preclinical finding relevant to research design: at high doses in animal models, it has been associated with interference with photoreceptor cone function — specifically a temporary yellowish tint to vision that is dose-dependent and reversible. The mechanism is proposed to involve AR binding in retinal cells.
This finding was cited as a reason for Andarine not advancing to human clinical trials vs Ostarine. For in vitro and animal research at moderate doses, this consideration does not apply, but researchers should be aware when designing in vivo protocols.