S-4 (Andarine)

Selective Androgen Receptor Modulators (SARMs) are a class of research compounds that bind to the androgen receptor (AR) with high affinity and selectivity. Unlike anabolic steroids, which activate the AR broadly across all tissues, SARMs are designed to exhibit tissue-selective activity — achieving anabolic effects in muscle and bone while minimising activity in tissues such as the prostate, liver, and sebaceous glands.

How SARMs Work

The androgen receptor is a nuclear receptor that, when activated by androgens (such as testosterone or DHT), translocates to the cell nucleus and regulates gene transcription. Anabolic steroids activate this receptor systemically, leading to well-documented side effects from off-target tissue activation.

SARMs achieve selectivity through two main mechanisms. First, their distinct chemical structure induces a unique conformational change in the AR upon binding, recruiting different co-activator and co-repressor proteins depending on the tissue. Second, because they are not substrates for 5α-reductase (the enzyme that converts testosterone to the more potent DHT), SARMs avoid amplification of androgenic activity in tissues that express this enzyme.

This tissue-selective mechanism is what makes SARMs of significant interest to pharmaceutical researchers investigating conditions such as muscle-wasting diseases, osteoporosis, and hypogonadism.

The Development of SARMs

The first-generation SARMs emerged from work by researchers at the University of Tennessee in the late 1990s. Professor James T. Dalton and his team synthesised Ostarine (MK-2866 / Enobosarm), which became the first SARM to enter human clinical trials. GTx Inc. subsequently ran multiple Phase II and Phase III trials investigating Ostarine for cancer cachexia (the POWER 1 and POWER 2 trials), producing the most comprehensive human pharmacokinetic and efficacy dataset for any SARM.

Subsequent generations of SARMs — including LGD-4033 (Ligandrol) by Ligand Pharmaceuticals, RAD-140 (Testolone) by Radius Health, and others — followed with varying degrees of clinical development. LGD-4033 entered Phase I trials in 2013 (Basaria et al., The Lancet), establishing clear evidence of dose-dependent lean mass gains and testosterone suppression in healthy men.

Classes of SARMs in Research

SARMs are typically categorised by their structural class:

• Non-steroidal SARMs: The majority of modern SARMs including Ostarine, LGD-4033, RAD-140, and S-4 (Andarine). These are synthetic non-steroidal molecules with no structural relationship to testosterone or DHT.
• Steroidal SARMs: YK-11 is notable for having a steroidal backbone (a C-19 steroid derivative), making it structurally distinct from other SARMs while also exhibiting myostatin inhibition via Follistatin upregulation.
• Other AR-modulating research compounds: Some compounds that are grouped informally with SARMs — such as Cardarine (GW-501516, a PPARδ agonist) and SR-9009 (a Rev-ErbA agonist) — are not technically SARMs as they do not bind to the androgen receptor, but are frequently studied alongside them.

What Does Published Research Show?

Clinical trial evidence for SARMs is in early stages but growing. Key findings from published literature include:

• LGD-4033: Basaria et al. (2013) demonstrated dose-dependent lean mass gains of 1.21 kg at 1 mg/day over 21 days in healthy men, with dose-dependent testosterone suppression recovering by day 56 post-dose.
• Ostarine: Multiple GTx Phase II and III cachexia trials demonstrated lean mass preservation and dose-dependent lean mass gains with low androgenic activity.
• RAD-140: A 2020 Phase I/II trial in breast cancer patients reported acceptable tolerability; preclinical primate studies showed anabolic effects with minimal prostate weight changes.
• S-4 (Andarine): GTx preclinical data demonstrated bone-protective and lean mass effects; early-phase human data was limited before the programme was discontinued.

Legal Status in the UK

SARMs are not controlled substances under the Misuse of Drugs Act 1971 in the United Kingdom. They are not licensed medicines under the Medicines Act 1968. As a result, they occupy a legal grey area: they can be purchased and possessed for research purposes but cannot be marketed or sold for human consumption.

Retailers must not make medical or health claims and must ensure products are labelled and sold strictly for research use. Importation for personal consumption may attract attention from HMRC or the MHRA depending on quantity and intent.

Frequently Asked Questions

Are SARMs the same as steroids?

No. While both bind to the androgen receptor, SARMs are non-steroidal (with the exception of YK-11) and are designed for tissue-selective AR activation. Anabolic steroids typically activate the AR non-selectively across all tissues. SARMs also lack the potential for conversion to oestrogen via aromatase that testosterone carries (though some suppression of endogenous testosterone is still observed with most SARMs).

Are SARMs legal to buy in the UK?

SARMs are not controlled under the Misuse of Drugs Act 1971. They can be purchased for research purposes. They may not be sold for human consumption under UK medicines law. Always purchase from a reputable supplier that clearly labels products as research chemicals.

Do SARMs suppress testosterone?

Published human trial data consistently shows that SARMs cause dose-dependent suppression of endogenous testosterone. The degree varies by compound: LGD-4033 showed marked suppression at higher doses in Basaria 2013; Ostarine showed milder suppression; S-23 showed near-complete suppression. Recovery appears to occur within weeks to months post-discontinuation across published trials.

What is the most studied SARM?

Ostarine (MK-2866 / Enobosarm) has the most extensive human trial dataset of any SARM, having progressed through Phase II and Phase III trials conducted by GTx Inc. LGD-4033 has the most robust Phase I human pharmacokinetic data from the Basaria et al. (2013) publication in The Lancet.