Ostarine

Enobosarm (also known as ostarine or GTX-024) is a nonsteroidal selective androgen receptor modulator (SARM) belonging to the aryl-propionamide chemical class. Unlike traditional anabolic steroids, it does not undergo aromatization to estrogen or reduction by 5α-reductase, giving it a distinct tissue-selective activity profile compared with testosterone or synthetic steroidal androgens.

Because it is a small, lipophilic nonsteroidal molecule with good oral bioavailability, enobosarm can be taken by mouth and reaches systemic circulation without requiring esterification or injection. Its selective binding to androgen receptors in certain tissues—while having comparatively less activity in others—has driven research interest across muscle wasting, bone health, and hormone-sensitive cancers, though long-term safety data in humans remain limited.

Human study: In a randomised double-blind placebo-controlled phase 2 trial in cancer patients with weight loss, both enobosarm groups showed statistically significant increases in total lean body mass compared with baseline by day 113, while the placebo group did not. The authors concluded that enobosarm may improve lean body mass without the toxicities associated with traditional androgens. (PMID 23499390)

Animal study: In vitro experiments with C2C12 and L6 muscle cell lines and in vivo rat studies showed that ostarine stimulates muscle cell proliferation and differentiation by increasing expression of myogenin, MyoD, and MyH, and this effect was mediated through androgen receptor and ERK1/2 kinase activation. Pharmacological blockade of the androgen receptor inhibited these stimulatory effects. (PMID 35457222)

Animal study: In ovariectomized rats with experimental tibial osteotomy, ostarine enhanced callus formation, increased callus density, accelerated bridging time, and elevated alkaline phosphatase expression, suggesting a positive effect on early bone healing. All treatment groups also showed increased gastrocnemius muscle weight, and partial increases in uterus weight were noted at higher exposures. (PMID 31531719)

Laboratory study: In isolated rat adipocytes, ostarine acted via the androgen receptor to downregulate leptin and adiponectin mRNA expression and reduce their secretion, with effects similar to testosterone on lipid metabolism regulation. This was the first report of ostarine affecting endocrine function of mature adipocytes in vitro. (PMID 31642815)

Laboratory study: In laboratory assays using Pseudomonas aeruginosa, ostarine significantly reduced pyocyanin virulence factor production without bactericidal activity by interfering with quorum sensing gene transcription and signalling molecule production. This study identified a potential anti-virulence application for ostarine unrelated to its androgenic activity. (PMID 34480092)

Human study: In the same phase 2 breast cancer trial, grade 3 or 4 drug-related adverse events occurred in 8–16% of patients and included elevated hepatic transaminases, hypercalcaemia, and fatigue. Four deaths were reported and judged unrelated to the study drug. (PMID 38342115)

Human study: A case report described a 31-year-old man who developed drug-induced hepatocellular liver injury—presenting with pruritus and dark urine—after using an over-the-counter muscle-building supplement containing enobosarm; liver injury resolved after discontinuation of the supplement. (PMID 35655632)

Human study: Metabolic profiling identified ten ostarine metabolites in human hepatocytes and in urine from confirmed users, including glucuronide and hydroxylated forms; the authors noted that cyanophenol-sulfate production may contribute to the mechanism of liver toxicity observed in regular users. Note: Doping/detection study; urine samples from six ostarine-positive cases and human hepatocyte incubations were analyzed. (PMID 39063049)

Animal study: In male Wistar rats, ostarine alone decreased submaximal endurance and increased myostatin gene expression in gastrocnemius muscle, while having no effect on maximal time to exhaustion, grip strength, or serum levels of luteinizing hormone, follicle-stimulating hormone, or testosterone. When combined with treadmill training, ostarine blunted the endurance-enhancing effect of exercise. (PMID 38451281)

Laboratory study: Using H9C2 cardiomyocyte cells, primary rat cardiac fibroblasts, and rat heart tissue, ostarine increased expression of the cardiomyopathy marker βMHC and, in male but not female fibroblasts, elevated fibrosis markers αSMA and fibronectin. Decreased cell viability and increased LDH cytotoxicity were observed, suggesting sex-specific cardiotoxic potential at high exposures. (PMID 37543162)

Limitations:

Human study: The POWER phase 3 trial design paper described that while enobosarm showed significant lean body mass improvements in phase 2, physical function improvements were inconsistent, and the trials were designed to address this gap using stair-climb power and DXA as co-primary endpoints in NSCLC patients. The authors acknowledged that these trials were pioneering regulatory methodology for cancer-associated muscle wasting endpoints. (PMID 27138015)

Animal study: In obese rats undergoing exercise, ostarine produced a modest reduction in serum cholesterol but did not show additive metabolic effects with exercise on most parameters including insulin sensitivity, leptin, and adiponectin. The authors noted that further research is needed given the limitations of a single dose level and the rat obesity model used. (PMID 37865959)

Open questions: Several important questions remain unanswered by the available evidence. It is unclear whether the lean-mass gains observed in cancer patients translate into durable improvements in physical function and survival. The degree of liver toxicity risk at various exposure levels—and whether metabolites such as cyanophenol-sulfate are causally responsible—has not been established in controlled studies. Sex-specific cardiac effects observed in rodent and cell models have not been evaluated in human populations. The interaction between ostarine and endurance-exercise adaptations requires further human study, as animal data suggest potentially counterproductive effects on submaximal endurance.

Finally, optimal patient selection by androgen-receptor expression level, cancer subtype, or baseline muscle status for therapeutic use remains undefined.