Modern nonsteroidal androgen research developed through medicinal chemistry, laboratory experiments and clinical investigation. Its history is not evidence that today's retail research products are safe for human use.
SARMs stands for selective androgen receptor modulators. The research aim is to investigate how compounds acting through the androgen receptor differ in their activity across tissues. “Selective” describes a research objective and observed properties under particular conditions, not a guarantee of no adverse effects.
Before SARMs: the problem researchers wanted to solve
In short: researchers wanted the muscle and bone effects of androgens without their effects on the prostate, skin, liver and cardiovascular system.
Testosterone and the synthetic anabolic steroids act on the androgen receptor wherever it occurs. Testosterone is also converted in the body to dihydrotestosterone, which is more potent in the prostate and skin, and to oestradiol. The pharmacology of these steroids, and the reasons their side effects are hard to separate from their wanted effects, is reviewed by Kicman in the British Journal of Pharmacology (2008).
For decades clinicians had patients who might benefit from an androgen acting mainly on muscle and bone: people losing muscle through cancer, HIV infection or age, and people with bone loss. That clinical gap is the reason the field exists. It was a medical question, not a sporting one.
1998: an early nonsteroidal-androgen milestone
In short: in 1998 a University of Tennessee group reported the first nonsteroidal compounds that activated the androgen receptor.
In Discovery of Nonsteroidal Androgens, Dalton and colleagues reported nonsteroidal compounds that bound the androgen receptor and activated receptor-mediated transcription in laboratory experiments. The molecules were related to aryl propionamide anti-androgens already used in prostate cancer research, modified so that they switched the receptor on rather than blocking it.
That publication marks an early milestone in this line of research. It did not establish the safety or effectiveness of the later products sold under the SARMs label.
1999: the concept gets a name
In short: the term “selective androgen receptor modulator” was set out in a 1999 commentary in the Journal of Clinical Endocrinology and Metabolism.
Negro-Vilar described SARMs as a new approach to androgen therapy, drawing on the example of the selective oestrogen receptor modulators that were already in clinical use. The idea was that a ligand could change the shape of the receptor in a way that recruits different partner proteins in different tissues, so that its effect depends on where it acts.
The 2000s: preclinical programmes
In short: through the 2000s several companies took candidate SARMs through animal studies, mostly in models of muscle and bone loss.
The Tennessee chemistry was developed by GTx Inc. Its compound S-4, later called Andarine, was tested in castrated male rats, where Gao and colleagues (Endocrinology, 2005) reported effects on muscle strength, body composition and bone with smaller effects on the prostate. Chen and colleagues reviewed the programme in Molecular Interventions the same year.
Other companies followed with their own scaffolds. Ligand Pharmaceuticals developed LGD-4033, later licensed to Viking Therapeutics, and Radius Health characterised RAD-140 in rodents and primates (Miller and colleagues, ACS Medicinal Chemistry Letters, 2011). None of these programmes was designed for bodybuilding.
2011: enobosarm studied in older adults
In short: enobosarm (Ostarine) became the first SARM with a published placebo controlled phase II trial.
A phase II enobosarm study examined body composition, physical function and safety in older men and postmenopausal women.
The move into clinical research matters, but so does the population. Results in a defined trial cannot be treated as promises for every age group or sporting goal.
2012: LGD-4033 human findings published
In short: a phase I study of LGD-4033 in healthy men measured safety, hormones and body composition over three weeks.
The LGD-4033 study examined healthy men under a controlled protocol. Its assessments included safety, hormone measurements and body composition.
This illustrates why a research history must include what was measured, rather than simply listing compounds as increasingly powerful generations.
2013: the function problem
In short: larger trials showed that adding lean mass was easier than improving physical function, which is what regulators look for.
A randomised phase II trial in patients with cancer related muscle wasting (Dobs and colleagues, Lancet Oncology, 2013) reported changes in lean body mass. The phase III programme that followed, whose design is described by Crawford and colleagues (Current Oncology Reports, 2016), met its lean mass goal but not its physical function goal, and no licence followed. That pattern, mass without a clear gain in function, recurs throughout the SARM literature.
Sport, testing and the grey market
In short: as the compounds became available online, anti-doping laboratories developed tests for them and product surveys found widespread mislabelling.
SARMs are prohibited at all times in sport under section S1.2 of the World Anti-Doping Agency list. Thevis and Schänzer (Molecular and Cellular Endocrinology, 2018) review how doping control laboratories detect them. Outside sport, Van Wagoner and colleagues (JAMA, 2017) analysed 44 products sold online as SARMs and found that many did not contain what the label stated. That finding is a large part of why batch testing matters in this category.
Later programmes asked different questions
In short: recent human studies of SARMs have mostly been in cancer, not muscle building.
The RAD-140 first-in-human study investigated a defined breast-cancer population. Enobosarm has also been studied in a randomised phase II trial in advanced breast cancer (Palmieri and colleagues, Lancet Oncology, 2024). Neither was a bodybuilding trial. Different development programmes have pursued different clinical questions; they cannot be collapsed into one story of proven gym benefits.
Why the history matters
In short: a finding belongs to the compound, population and question that were studied.
Check the compound, date, population and research question before applying a finding. A milestone for one candidate does not demonstrate effectiveness or safety for another compound or for a retail formulation.
For definitions, start with SARMs 101. For the difference between an investigation and an approved treatment, read SARMs in clinical development.
Frequently asked questions
When were SARMs discovered? The first nonsteroidal androgen receptor agonists were reported in 1998, and the term SARM was set out in 1999.
Who developed the first SARMs? The founding chemistry came from James Dalton's group at the University of Tennessee and was developed by GTx Inc. Ligand Pharmaceuticals and Radius Health ran separate programmes.
Has any SARM been approved as a medicine? No. After more than 25 years of research, no SARM holds a marketing authorisation in the UK or anywhere else.
Were SARMs designed for sport? No. Every major programme targeted a medical problem such as muscle wasting, bone loss or cancer.
Research products are not for human consumption. This timeline provides historical context, not use instructions.
Sources
- Kicman AT (2008). Pharmacology of anabolic steroids. Br J Pharmacol. PubMed 18500378
- Dalton JT et al. (1998). Discovery of nonsteroidal androgens. Biochem Biophys Res Commun. PubMed 9514878
- Negro-Vilar A (1999). Selective androgen receptor modulators (SARMs): a novel approach to androgen therapy for the new millennium. J Clin Endocrinol Metab. PubMed 10522980
- Gao W et al. (2005). Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats. Endocrinology. PubMed 16099859
- Chen J et al. (2005). Discovery and therapeutic promise of selective androgen receptor modulators. Mol Interv. PubMed 15994457
- Miller CP et al. (2011). Design, synthesis, and preclinical characterization of the selective androgen receptor modulator (SARM) RAD140. ACS Med Chem Lett. PubMed 24900290
- Dalton JT et al. (2011). The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women. J Cachexia Sarcopenia Muscle. PubMed 22031847
- Basaria S et al. (2013). The safety, pharmacokinetics, and effects of LGD-4033 in healthy young men. J Gerontol A Biol Sci Med Sci. PubMed 22459616
- Dobs AS et al. (2013). Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. PubMed 23499390
- Crawford J et al. (2016). Study design and rationale for the phase 3 clinical development program of enobosarm (POWER trials). Curr Oncol Rep. PubMed 27138015
- Van Wagoner RM et al. (2017). Chemical composition and labeling of substances marketed as selective androgen receptor modulators and sold via the internet. JAMA. PubMed 29183075
- Thevis M, Schänzer W (2018). Detection of SARMs in doping control analysis. Mol Cell Endocrinol. PubMed 28137616
- LoRusso P et al. (2022). A first-in-human phase 1 study of a novel selective androgen receptor modulator (SARM), RAD140, in ER+/HER2- metastatic breast cancer. Clin Breast Cancer. PubMed 34565686
- Palmieri C et al. (2024). Activity and safety of enobosarm in androgen receptor-positive, oestrogen receptor-positive, HER2-negative advanced breast cancer (Study G200802). Lancet Oncol. PubMed 38342115
- WADA Prohibited List 2026.
Related guides
- What are SARMs? The research explained
- PCT After SARMs: What the Research Says, UK 2026
- Are SARMs Safe? What the Evidence Says About Side Effects, UK 2026
- SARMs vs Anabolic Steroids vs Prohormones: The Pharmacology and the Law, UK 2026
- SARMs Capsules vs Liquid: Stability, Dosing Accuracy and Testing, UK 2026
- Lab Testing