What Is S-4 (Andrarine)

S-4, marketed as andarine, is an orally bioavailable, non-steroidal selective androgen receptor modulator (SARM). Andarine is a partial agonist of the androgen receptor.

S-4 like other SARMS were developed in the early 2000s, in an attempt to overcome the pharmacologic and pharmacokinetic limitations of steroidal androgen receptor agonists (i.e., testosterone and DHT), which have known associations with liver and heart disease .

Compound S-4 was used in animal studies but was abandoned before any Phase I human clinical trials, due to visual impairments. These effects occur as the S-4 molecule binds to the receptors in the eye; the more aggressive the binding, the more discomfort that is experienced. Visual disturbances were found to be so common, due to unique mechanistic action, for the drug that the trials were abandoned.

How Does S4 Andarine Work

One of the suggested mechanisms of S4, is that it completely blocks the binding of DHT. Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex hormone. Relative to testosterone, DHT is considerably more potent as an agonist of the androgen receptor.

S-4 has a high androgen receptor (AR) binding affinity. Studies have shown that S-4 is less potent and efficacious than testosterone propionate (TP) in androgenic activity, but their anabolic activity was similar to or greater than that of TP.

S-4 is a full androgen receptor agonist in muscle tissue, and a partial agonist in the prostate . Thus, S-4 potently stimulates muscle growth, but is unable to maintain prostate size. Testosterone stimulates muscle and prostate growth to the same extent.  S-4 causes significant luteinizing hormone (LH) or follicle stimulating hormone suppression.

S-4 (andarine) Benefits

Although many investigational studies have been conducted, more research is ongoing and in the early stages of development. The development of SARMS for clinical and therapeutic use as an androgen alternative, is promising based on preclinical data.

Unlike anabolic steroids, which bind to androgen receptors in many tissues all over the body, individual SARMs selectively bind to androgen receptors in certain tissues, but not in others. Nonetheless, they are still exhibit androgenic and anabolic effects.

SARMS are not anabolic steroids; rather, they are synthetic ligands that bind to androgen receptors. Depending on their molecular structure, they act as agonists, partial agonists, and antagonists. It is thus in a selective manner, that SARMS modulate or mediate coregulators and transcription factors or signaling cascade proteins to promote anabolic activity.

Studies have shown S-4 is a full androgen receptor agonist in muscle tissue, and a partial agonist in the prostate, making it an ideal candidate as an alternative to steroidal androgen receptor agonists (i.e., testosterone and DHT), due to associated adverse effects on liver, heart, and fertility.

It should be noted, that although SARMS like S4 increase androgen activity, it is not a viable candidate for hormone replacement therapy, since it does not aromatize into Estrogen.