S-4 (Andarine)

S-4, designated Andarine, is a first-generation non-steroidal selective androgen receptor modulator developed by GTx, Inc. as part of the foundational research program that also produced Ostarine. Originally investigated for the treatment of osteoporosis, muscle wasting, and benign prostatic hyperplasia (BPH), Andarine holds a unique position as one of the earliest SARMs to demonstrate the feasibility of tissue-selective androgen receptor modulation in vivo. While newer SARMs have surpassed it in raw anabolic potency, S-4 retains a dedicated research following for its distinctive cutting and physique-refining properties.

S-4 binds the androgen receptor as a partial agonist in muscle and bone tissue, with preclinical data demonstrating approximately one-third the binding affinity of testosterone. However, its tissue selectivity is notably favorable: S-4 produces minimal prostate stimulation while maintaining robust anabolic activity in skeletal muscle and anti-resorptive effects in bone. In the BPH research context, S-4 actually demonstrated anti-androgenic effects in prostate tissue — functioning as a competitive AR antagonist in that organ — while simultaneously building muscle mass, a dual-action profile unique among SARMs.

The research literature consistently highlights S-4's strength in cutting and body recomposition protocols. Researchers report enhanced vascularity, increased muscle hardness and definition, accelerated fat oxidation — particularly in stubborn adipose deposits — and lean tissue preservation during caloric deficit. S-4 produces a distinctive "dry" aesthetic, with reduced subcutaneous water retention that enhances visual muscle separation. It is less suited for pure mass-gaining protocols where RAD-140 or LGD-4033 would be more effective.

S-4 is appropriate for beginner-to-intermediate researchers focused on cutting, recomposition, or physique refinement. Its moderate potency and well-documented profile make it an accessible introduction to the SARM class, though Ostarine is generally preferred as a first compound. Andarine excels in caloric-deficit research where the primary objectives are fat loss, lean tissue sparing, and visual physique improvement. It stacks exceptionally well with Cardarine for enhanced fat oxidation and endurance.

S-4 has an elimination half-life of approximately 4–6 hours, requiring split dosing — typically 2–3 times daily — for stable plasma concentrations. Oral bioavailability is high. Testosterone suppression is mild to moderate. The most discussed side effect of S-4 is a transient visual disturbance — a yellow tint to vision, particularly in low-light conditions — caused by S-4 binding to retinal receptors. This effect is dose-dependent, fully reversible upon cessation, and typically managed by using a 5-days-on / 2-days-off dosing protocol or by reducing the daily dose. PCT is recommended for cycles exceeding 6 weeks. Typical research protocols range from 25–50mg daily (split into 2–3 doses) for 6–8 weeks.