Limited · human
This case report describes a 54-year-old male who presented to the emergency department with acute left upper quadrant pain and vomiting, and was found to have atraumatic splenic rupture (ASR) — a rare, potentially fatal condition. The patient had recently been using two performance-enhancing compounds: MK-677 (ibutamoren), a growth hormone secretagogue, and RAD-140 (testolone), a selective androgen receptor modulator (SARM). CT imaging confirmed a large perisplenic hematoma. Initial management with splenic artery embolization provided only transient stabilization, and the patient ultimately required emergency laparotomy with total splenectomy. Histopathology revealed extensive splenic infarction and features suggestive of an underlying vascular malformation. The authors speculate — without establishing causation — that the pharmacological effects of RAD-140 and MK-677 on androgen receptor signalling and IGF-1 pathways may have contributed to splenic complications, drawing an analogy to the known association between anabolic steroids and peliosis. No prior literature directly links these compounds to splenic pathology. The report highlights the importance of prompt diagnosis and surgical management of ASR. Key limitations include the single-patient design, inability to confirm causality, and presence of a potential pre-existing vascular malformation as a confounding factor.
Animal only
This mouse study examined how acute restraint stress (30 minutes) interferes with hunger-driven food-seeking behavior and what interventions can reverse this effect. Using a conflict-based open-field feeding paradigm, researchers found that restraint stress abolished the increases in food seeking and intake normally observed in fasted mice. Two pharmacological interventions — intraperitoneal diazepam (an anxiolytic) and MK-677 (a ghrelin receptor agonist) — both reversed this stress-induced suppression of feeding behavior, though through apparently distinct neural mechanisms. To map neural correlates, the study measured c-Fos (a marker of neuronal activation) and phosphorylated pyruvate dehydrogenase (pPDH, a marker of neuronal inhibition) in the paraventricular hypothalamic nucleus (PVN). Diazepam reduced restraint-induced c-Fos expression in the PVN, suggesting anxiolysis works via suppressing stress-driven PVN activation, while MK-677 increased pPDH, indicating a separate feeding-drive mechanism. Notably, refeeding after fasting produced a pPDH-dominant PVN pattern and also reduced anxiety-related behaviors, suggesting physiological restoration of energy balance may itself confer stress resilience. Key limitations include exclusive use of a mouse model, the use of a single stress paradigm, and the lack of direct causal circuit manipulations. Findings are not directly applicable to humans without further study.
Neuroscience research · Nov 2025DOI ↗ Limited · human
This study investigated the detection of ibutamoren (MK-677), a growth hormone secretagogue, in human hair samples to aid forensic interpretation of anti-doping hair test results. Two scenarios were examined: (1) a single 10 mg oral dose administered to a male volunteer, with hair collected 4 weeks later; and (2) hair collected from an individual who had consumed 60 capsules of 10 mg ibutamoren over 90 days, also sampled 4 weeks after discontinuation. Researchers developed a liquid/liquid extraction method using bicalutamide-D4 as an internal standard, with a validated linear range of 0.5–250 pg/mg and a limit of detection of 0.1 pg/mg. The study found that a single 10 mg dose produced a positive hair result at 1.3 pg/mg in the 0–1 cm segment, while the prolonged-use scenario yielded 224 pg/mg in the 0–4 cm segment. The authors conclude that these findings establish, for the first time, ibutamoren's incorporation into human hair and provide reference concentration ranges to support interpretation of hair test results in anti-doping proceedings. Key limitations include the very small sample size (essentially two subjects) and the non-controlled nature of the second case.
Clinica chimica acta; international journal of clinical chemistry · Aug 2025DOI ↗ Limited · human
This paper presents a case report of a man in his early 30s who developed transaminitis (elevated liver enzymes) after taking MK-677, an oral growth hormone secretagogue, for approximately two months. MK-677 has been growing in popularity as a performance-enhancing supplement. The patient was otherwise healthy, with no other apparent causes for liver injury identified. Following discontinuation of the supplement, liver function tests gradually returned to normal levels, suggesting a causal relationship between MK-677 use and the hepatotoxic event. The authors highlight that while known side effects of MK-677 include oedema, increased appetite, and muscle pain, reports of hepatotoxicity associated with its use are rare. This case adds to the limited literature on potential adverse hepatic effects of MK-677. Key limitations include the single-patient design, lack of a liver biopsy or formal causality assessment score (e.g., RUCAM), inability to fully exclude confounders such as contaminants in the supplement, and the inherent difficulty in establishing definitive causality from a single case report.
BMJ case reports · Jul 2025DOI ↗ Animal only
This mouse study investigated whether intranasal administration of ghrelin, GHRP-6, or MK-0677 could activate the brain's ghrelin signaling system. Researchers first screened compounds and doses by measuring food intake after intranasal application. Of the three compounds tested, only GHRP-6 at a specific dose increased food intake without adverse effects and was selected for detailed analysis. Investigators then examined meal patterns, neuronal activation in the arcuate nucleus of the hypothalamus using Fos mapping, and neurochemical identity of activated neurons using RNAscope in situ hybridization. They also measured serum growth hormone (GH) levels. The study found that intranasal GHRP-6 increased food intake by raising both meal frequency and meal size. Fos expression in the arcuate nucleus was significantly elevated compared to saline controls, and activated neurons showed co-expression with GHSR, AgRP, and GHRH mRNA markers, implicating circuits involved in feeding and GH regulation. Serum GH levels were also elevated following intranasal GHRP-6. Limitations include exclusive use of a mouse model, a single species and sex are not specified, and the absence of human or pharmacokinetic data, meaning translation to clinical settings remains uncertain.
Endocrinology · Feb 2025DOI ↗ In vitro
This study investigated whether ibutamoren (IBU) — a compound known primarily as a growth hormone secretagogue — might also act as an inhibitor of the MDM2-p53 interaction, a pathway dysregulated in roughly half of human cancers. MDM2 normally tags the tumour suppressor p53 for degradation; blocking this interaction is a recognized anticancer strategy. The researchers first used in silico molecular modelling to predict that IBU binds favorably to the p53-binding pocket of MDM2 and exhibits a low estimated IC50 for MDM2 inhibition. They then tested IBU on immortalized human cancer cell lines in vitro, finding reduced cell viability in lines with an intact, functional MDM2-p53 pathway but not in lines carrying damaging mutations in this pathway. RT-qPCR analysis supported this pattern, showing differential expression of two p53 target genes in wild-type but not mutant cell lines after IBU treatment. Key limitations include exclusive reliance on cell-line models (no animal or human data), use of immortalized rather than primary cells, and the preliminary, exploratory nature of the work. The authors conclude that IBU shows early-stage anticancer activity potentially mediated through the MDM2-p53 axis and warrants further mechanistic investigation.
Basic & clinical pharmacology & toxicology · Jan 2025DOI ↗ Limited · human
This case report describes a 40-year-old male who developed bilateral gynecomastia and biochemical hypogonadotropic hypogonadism after approximately six months of using commercially available performance-enhancing supplements. Laboratory analysis of the three supplements identified several banned performance-enhancing drugs (PEDs): RAD-140 (a selective androgen receptor modulator), MK-677 (a growth hormone secretagogue), and cardarine. In vitro testing also revealed undisclosed hormones — testosterone, estradiol, and growth hormone — present in all three products. Liquid chromatography-mass spectrometry further identified an uncharacterized compound eluting near the testosterone peak. Upon cessation of all supplements, the patient experienced full clinical and biochemical resolution of his symptoms, including normalization of gonadotropin and testosterone levels. The authors argue this case underscores the importance of clinicians considering commercially available supplements as potential covert sources of exogenous PEDs and steroid hormones. Key limitations include the single-patient design, which precludes generalization, the inability to isolate which specific compound(s) caused the adverse effects, and the lack of confirmed identity of the uncharacterized coeluting compound.
JCEM case reports · Aug 2024DOI ↗ Animal only
This study investigated whether MK-0677 (ibutamoren), an orally active, non-peptide growth hormone secretagogue that activates the ghrelin receptor, could be detected in equine hair following oral administration to a single Thoroughbred racehorse. Researchers extracted MK-0677 and its O-dealkylated metabolite from mane and tail hair samples using an established method for prohibited substances, then analyzed them by liquid chromatography tandem mass spectrometry (LC-MS/MS). The study found that MK-0677 was detectable in all collected hair samples, with a detection window of up to 209 days in mane hair and 358 days in tail hair. A follow-up wash procedure confirmed true internal incorporation of the compound rather than mere surface contamination. Wash criteria analyses suggested that hair samples collected at later time points (≥52 days post-administration) reflected internal incorporation via the bloodstream, while the earliest sample (2 days) showed a combination of internal incorporation and external deposition via sweat and sebum. A key limitation is that the study involved only one horse, restricting generalizability. The findings are relevant to anti-doping efforts in equine sports, highlighting the long detection window MK-0677 may afford in hair matrices.
Drug testing and analysis · Dec 2022DOI ↗ Limited · human
This case report tracked a single 25-year-old recreationally active male who self-administered LGD-4033 (a selective androgen receptor modulator) and MK-677 (a growth hormone secretagogue) daily for five weeks. Blood work and body composition (via DXA) were collected before, during, and after the cycle, while muscular strength and skeletal muscle androgen-related biomarkers were assessed during the cycle and compared cross-sectionally against data from non-using trained males. The study observed increases in total body mass, lean mass, and fat mass during the cycle, alongside adverse changes in bone mineral content and density, serum lipids (notably a 40% rise in LDL and a 36% drop in HDL), and liver enzymes (ALT rose over 200%). Total and free testosterone and sex hormone-binding globulin fell markedly during the cycle. Most biomarkers returned toward baseline post-cycle, though total cholesterol, LDL, total fat mass, and bone area did not fully recover. Follicle-stimulating hormone remained below clinical reference ranges even post-cycle. Compared with non-users, the subject showed higher intramuscular testosterone and dihydrotestosterone but lower androgen receptor content, alongside greater strength. Key limitations include the single-subject design, lack of a control group, and reliance on cross-sectional comparisons for intramuscular and strength data, making causal inferences unreliable.
Experimental physiology · Nov 2022DOI ↗ Animal only
This study investigated the metabolic profile of ibutamoren (MK-0677) — an orally active, non-peptide growth hormone secretagogue — in thoroughbred horses, with the goal of supporting anti-doping detection efforts. Researchers administered ibutamoren orally to horses and collected biological samples, which were analyzed using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) to identify and characterize the parent compound and its metabolites. The study identified 22 metabolites in total: 17 Phase I metabolites (including mono- and di-hydroxylated forms, dissociated side chain products such as a benzyl group and 2-amino-2-methylpropanamide, and hydrogenated metabolites) and 5 Phase II metabolites (glucuronic acid conjugates; no sulfate conjugates were detected). The study reported that major metabolites were detectable up to 96 hours post-administration, while the parent compound ibutamoren itself persisted for up to 72 hours. The authors conclude that these findings provide a useful metabolic reference framework to help detect illicit use of ibutamoren in competitive equine sports. Key limitations include the use of an animal model (horses only), meaning findings may not directly translate to human metabolism or human anti-doping contexts.
Rapid communications in mass spectrometry : RCM · Sep 2022DOI ↗ Preclinical
This study investigated how synthetic and endogenous ligands bind to and activate the growth hormone secretagogue receptor (GHS-R), a G-protein coupled receptor involved in growth hormone (GH) release and appetite regulation. Using radiolabeled ligand-binding assays, calcium-response (aequorin-based) assays, GH release assays in mice, receptor chimeras (human/puffer fish domain swaps), and site-directed mutagenesis, researchers characterized the structural basis of ligand-receptor interactions. The study found that synthetic agonists MK-0677 and GHS-25 displayed high binding affinity and, notably, greater in vivo GH secretagogue activity compared to the endogenous peptide ghrelin. GHS-R knockout mice showed complete abolition of activity, confirming receptor specificity. Chimera analysis identified the C-terminal region, particularly transmembrane domain 6 (TM6), as critical for ligand-dependent activation. Site-directed mutagenesis pinpointed residues D99 and W276 as essential for ligand binding, while E124 was selectively important for MK-0677, and F279 was preferentially involved in ghrelin and GHS-25 interactions. The study is primarily mechanistic and largely preclinical (in vitro and animal models), limiting direct translation to human therapeutic contexts. Its findings advance structural understanding of GHS-R and may inform future drug design efforts.
Journal of translational internal medicine · Jun 2022DOI ↗ Limited · human
This study compared the growth hormone (GH) response elicited by a single oral dose of LUM-201 (ibutamoren/MK-0677), a GH secretagogue receptor agonist, to responses from standard diagnostic GH stimulation tests (arginine, glucagon, clonidine, L-dopa, and insulin-induced hypoglycemia) in 68 pediatric subjects enrolled in a pediatric growth hormone deficiency (PGHD) clinical trial. The study found that LUM-201 produced significantly greater GH responses than the conventional secretagogues, with median peak GH of 15.0 ng/mL versus 5.5 ng/mL for standard tests (p-value not fully captured in abstract but reported as statistically significant). Notably, the larger GH responses to LUM-201 were most pronounced in subjects who also showed higher peak GH responses to conventional testing, suggesting a functional somatotroph reserve may be required. The authors concluded that LUM-201 may represent a potential oral treatment alternative to injectable recombinant human GH (rhGH) in a subset of PGHD patients who demonstrate adequate acute GH responses to LUM-201. Limitations include the lack of a placebo-controlled design, relatively small sample size, and the single-dose comparison design which does not assess long-term growth outcomes.
Hormone research in paediatrics · Mar 2022DOI ↗ Animal only
This study investigated the metabolism of MK-0677 (ibutamoren mesylate), an orally active non-peptide growth hormone secretagogue, in horses to support equine doping control efforts. Researchers conducted both in vitro incubations and in vivo oral administration to two Thoroughbred racehorses, then used liquid chromatography high-resolution mass spectrometry (LC-HRMS) and LC-tandem mass spectrometry to identify and profile metabolites in urine and plasma. Fourteen phase I metabolites were identified in vitro; 13 were subsequently detected in post-administration urine and nine in plasma, along with the parent compound in both matrices. The study found that an O-dealkylated metabolite of MK-0677 showed the longest detection window in both urine and plasma, making it the recommended analytical target for doping control laboratories. Both MK-0677 and this key metabolite were found to be excreted predominantly in unconjugated form. Limitations include the very small sample size (n=2 horses) and the fact that findings are restricted to equine species, meaning results cannot be directly extrapolated to human metabolism or doping detection in human sport.
Drug testing and analysis · Mar 2022DOI ↗ Review
This narrative review examines the potential adjunctive role of growth hormone secretagogues (GHS) in managing body composition changes associated with male hypogonadism and metabolic syndrome. The authors acknowledge that while testosterone replacement therapy remains the standard of care for hypogonadism, its body composition benefits are inconsistent across patient populations. The review surveys existing literature on five GHS compounds — sermorelin, GHRP-2, GHRP-6, ibutamoren (MK-677), and ipamorelin — noting that all stimulate growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion and may improve body composition metrics such as reducing fat mass and attenuating muscle atrophy. The authors also explore their potential utility in eugonadal males with metabolic syndrome or subclinical hypogonadism. A major limitation explicitly acknowledged by the authors is the scarcity of robust clinical trial data evaluating these compounds specifically in hypogonadal men. The review concludes that while GHS show theoretical and preliminary promise as complementary agents, the current evidence base is insufficient to draw firm clinical conclusions, and the authors call for future controlled investigations. No new primary data are presented.
Translational andrology and urology · Mar 2020DOI ↗