S4 (Andarine)

Overview

S4, also known as Andarine or GTx-007, is a non-steroidal selective androgen receptor modulator developed by GTx, Inc. as part of the same research program that produced Ostarine (MK-2866). Andarine was among the first SARMs to be characterized in preclinical studies and played an important role in establishing the proof of concept for tissue-selective androgen receptor modulation. While it was eventually superseded in GTx’s clinical development pipeline by Ostarine, Andarine remains a scientifically significant compound with a substantial preclinical evidence base.

The compound emerged from a medicinal chemistry campaign that screened thousands of non-steroidal AR ligands for anabolic activity in muscle and bone with minimal stimulation of the prostate. Andarine showed promising tissue selectivity in early animal studies, maintaining approximately 30% to 40% of the anabolic activity of testosterone propionate in the levator ani muscle while producing less than 10% of testosterone’s prostate stimulation. This separation ratio, while not as dramatic as some later SARMs, was sufficient to establish the pharmacological viability of the SARM concept.

Mechanism of Action

Andarine binds to the androgen receptor as a partial agonist. This is a critical distinction from full agonists like testosterone and from other SARMs that approach full agonist efficacy in muscle tissue. As a partial agonist, Andarine produces submaximal receptor activation even at saturating concentrations. In tissues where androgen receptor density is high and full activation is the normal physiological state (such as the prostate), partial agonism means Andarine cannot match the stimulatory effects of endogenous androgens. In muscle, where partial agonism may still be sufficient to drive meaningful anabolic transcription, the compound can produce disproportionate benefit.

The partial agonist profile also means that Andarine can function as a competitive antagonist in the presence of high endogenous androgen levels. By occupying AR binding sites without fully activating them, the compound can effectively reduce androgenic stimulation of target tissues. This property has been explored in preclinical models of benign prostatic hyperplasia (BPH), where Andarine reduced prostate weight without eliminating androgen signaling entirely.

Andarine’s pharmacokinetics in animal models show rapid oral absorption, with peak plasma concentrations reached within one to two hours. The half-life is relatively short, approximately four to six hours in rats, which has implications for dosing frequency. Metabolism occurs through oxidative and conjugative pathways, with several metabolites identified in preclinical species.

Research Summary

The preclinical evidence base for Andarine includes several important studies. In castrated male rats, Andarine restored levator ani muscle weight to near-sham levels while producing only modest increases in prostate and seminal vesicle weight. This tissue-selective profile was maintained across a range of doses, establishing the compound as a true SARM in the pharmacological sense.

In ovariectomized female rats (a model of postmenopausal bone loss), Andarine prevented bone mineral density loss and maintained bone strength as effectively as DHT, without producing the virilizing effects of the androgen. This finding supported the potential utility of SARMs in osteoporosis, a therapeutic area where the anabolic effects of androgens are desired but the masculinizing effects are unacceptable.

Studies in intact male rats demonstrated that Andarine could reduce prostate weight when administered at doses that maintained muscle mass, consistent with its partial agonist profile. This observation led to research exploring Andarine as a potential treatment for BPH, where the goal is to reduce prostate size while preserving lean mass and physical function.

Despite these promising preclinical results, GTx chose to advance Ostarine rather than Andarine into clinical trials, reportedly due to Ostarine’s superior tissue selectivity and more favorable pharmacokinetic profile. No human clinical trial data for Andarine have been published, though the compound has been detected in anti-doping analyses of athlete samples, confirming that it is used in non-clinical contexts.

Dosing in Published Research

S4 (andarine) is a selective androgen receptor modulator. It has not been the subject of published human clinical trials, so no controlled study has established a dose for it in people. Specific S4 figures circulating in forums or vendor material are not derived from human research and are therefore not reported here.

Safety and Side Effects

The most widely discussed side effect associated with Andarine is a visual disturbance described as a yellow tint to vision and difficulty adapting to changes in light conditions, particularly at night. This effect has been attributed to Andarine’s binding to retinal receptors, though the precise molecular target has not been definitively identified. Some researchers have proposed that the compound or a metabolite interacts with the retinal photoreceptor system, possibly through off-target binding to retinal androgen receptors or a distinct receptor in the visual pathway.

The visual side effect appears to be dose-dependent and reversible upon discontinuation. Reports from the research community suggest it is most prominent at doses exceeding 50 mg daily and resolves within one to two weeks of stopping administration. No permanent visual damage has been reported, though the absence of formal ophthalmological studies means that subclinical effects on retinal function cannot be excluded.

Hormonal suppression is expected based on Andarine’s AR agonist activity. User reports describe dose-dependent testosterone suppression, with recovery generally occurring within four to six weeks of discontinuation. HDL cholesterol reductions have been reported at doses commonly used in the research community (25 to 75 mg daily).

No formal toxicology studies have been published, and the safety of Andarine in humans has not been evaluated through regulatory processes. Hepatotoxicity data are unavailable from controlled studies, though user-reported bloodwork has not consistently shown liver enzyme elevations at commonly used doses.

Current Research Status

Andarine is an investigational compound that was not advanced to clinical trials by its developer. It has no approved medical indications and is prohibited by WADA. The compound remains available through research chemical suppliers and continues to be studied in academic laboratories investigating SARM pharmacology, androgen receptor biology, and tissue-selective androgen signaling. Its historical importance as one of the first well-characterized non-steroidal SARMs ensures its continued relevance in the scientific literature, even as newer compounds with potentially superior profiles have emerged.

Further reading: For a comparison of two related selective androgen receptor modulators, see RAD-140 vs LGD-4033: Comparing Two Researched SARMs.

Frequently Asked Questions