Key papers ✓ 4✗ 1? 3

• ✗ Negative human trialJ Clin Endocrinol Metab · 1998

  Growth hormone status during long-term hexarelin therapy.

  Humanssize not reported16 weeks of treatment, assessed to week 20

  Open longitudinal study of 16 weeks of twice-daily s.c. hexarelin (1.5 micrograms/kg) plus 4-week follow-up

  In healthy elderly adults given hexarelin twice daily for 16 weeks, the GH response fell by about 45% (partially reversible), and IGF-I, body fat, lean mass and bone density did not change.

  Key resultMean AUCGH fell from 19.1 micrograms/L.h at week 0 to 10.5 at week 16 (P<0.01 vs baseline) and recovered to 19.4 at week 20; IGF-I unchanged (P = 0.24)

  Study details

  Studied

  Adults given long-term hexarelin

  Compared with

  Baseline (no separate control group)

  Main outcome

  GH response (AUC of GH) to hexarelin; IGF-I, bone markers, body composition

  Sample

  Number of subjects not stated in abstract

  Authors' conclusion

  Chronic hexarelin caused a partial and reversible attenuation of the GH response; its biological impact on the GH-IGF-I axis seemed minimal. Therapeutic potential needs further investigation.

  Limitations

  Number of subjects not stated in abstract; no control group.

  DOI 10.1210/jcem.83.5.4812PubMed 9589671
• ✓ Positive human trialEur J Pharmacol · 2002

  Effects of acute hexarelin administration on cardiac performance in patients with coronary artery disease during by-pass surgery.

  Humans24 peoplePlacebo-controlledAcute; monitored up to 90 min

  Placebo-controlled acute-administration study versus GHRH and rhGH

  In 24 men undergoing bypass surgery, a single IV dose of hexarelin (but not GHRH, GH or placebo) acutely increased ejection fraction, cardiac index and output for up to 90 minutes.

  Key resultHexarelin increased left ventricular ejection fraction, cardiac index and cardiac output (all P<0.001) up to 90 min; GHRH, rhGH and placebo had no hemodynamic effect

  Study details

  Studied

  Male patients with coronary artery disease undergoing by-pass surgery under general anesthesia

  Compared with

  Placebo, GHRH, recombinant human GH

  Main outcome

  Left ventricular ejection fraction, cardiac index, cardiac output and hemodynamics

  Sample

  24 male patients with coronary artery disease

  Authors' conclusion

  Acute hexarelin clearly improved cardiac performance in these patients; the effect was not shared by GHRH or rhGH, suggesting it is not mediated by GH and more likely reflects cardiovascular GH secretagogue receptors.

  Limitations

  Acute, intraoperative setting in a small group.

  DOI 10.1016/s0014-2999(02)01934-9PubMed 12144941
• ✓ Positive human trialClin Endocrinol (Oxf) · 1995

  Intranasal administration of the GHRP hexarelin accelerates growth in short children.

  Humans8 peopleNo control groupUp to 8 months

  Uncontrolled long-term treatment study (intranasal hexarelin 60 micrograms/kg three times daily)

  In 8 short prepubertal children (uncontrolled), intranasal hexarelin for up to 8 months raised IGF-I and growth velocity (5.3 to 8.3 cm/year).

  Key resultIGF-I rose from 10.4 to 14.1 nmol/l (P < 0.004); growth velocity rose from 5.3 to 8.3 cm/year (P < 0.0001)

  Study details

  Studied

  Prepubertal short children

  Compared with

  Own baseline

  Main outcome

  IGF-I, linear growth velocity

  Sample

  8 prepubertal short children aged 4-11.6 years

  Authors' conclusion

  Long-term intranasal hexarelin had GH/IGF-I stimulating, anabolic and growth-promoting effects, seemingly without undesirable side-effects, suggesting clinical potential.

  Limitations

  Only 8 children and no control group.

  DOI 10.1111/j.1365-2265.1995.tb02929.xPubMed 8548949
• ? Inconclusive human RCTEur J Endocrinol · 2002

  Impact of two or three daily subcutaneous injections of hexarelin, a synthetic growth hormone (GH) secretagogue, on 24-h GH, prolactin, adrenocorticotropin and cortisol secretion in humans.

  HumansSix normal young menRandomized24-hour sampling periods

  Intermittent s.c. hexarelin schedules (two vs three daily injections) with 24-h hormone sampling

  In 6 healthy young men, 2-3 daily injections raised 24-h GH without changing IGF-I, prolactin, ACTH or cortisol over a day, while an IV dose raised GH, prolactin, ACTH and cortisol.

  Study details

  Studied

  Six healthy young men

  Compared with

  Baseline and two vs three injection schedules

  Main outcome

  24-h GH, PRL, ACTH and cortisol secretion

  Authors' conclusion

  Two or three daily s.c. injections increased 24-h GH secretion equally, selectively amplifying GH pulse mass without altering prolactin or ACTH/cortisol secretion; IGF-I was not changed by these 1-day schedules.

  Limitations

  Only six men; 1-day treatment schedules.

  DOI 10.1530/eje.0.1460310PubMed 11888836
• ? Inconclusive human trialClin Endocrinol (Oxf) · 1999

  The effect of chronic hexarelin administration on the pituitary-adrenal axis and prolactin.

  Humanssize not reported16 weeks plus 4 weeks after

  Twice-daily s.c. hexarelin (1.5 micrograms/kg) for 16 weeks, with follow-up

  During 16 weeks of twice-daily hexarelin, prolactin responses did not change and the cortisol response actually decreased (recovering after stopping), suggesting no adrenal or prolactin over-stimulation at this dose.

  Key resultCortisol AUC fell from 1506 to 1222 nmol/l/h at 16 weeks (P < 0.05) and returned to 1586 at week 20; prolactin AUC unchanged (P = 0.35)

  Study details

  Studied

  Adults given chronic hexarelin

  Compared with

  Baseline (no separate control group)

  Main outcome

  ACTH, cortisol and prolactin responses; cortisol-binding globulin and urinary free cortisol

  Sample

  Number of subjects not stated in abstract

  Authors' conclusion

  This hexarelin regimen did not over-stimulate the pituitary-adrenal axis or prolactin; cortisol response actually decreased, probably not clinically significant, mechanism needs study.

  Limitations

  Number of subjects not stated; no control group.

  DOI 10.1046/j.1365-2265.1999.00609.xPubMed 10341859
• ✓ Positive animalPeptides · 2019

  Hexarelin attenuates atherosclerosis via inhibiting LOX-1-NF-κB signaling pathway-mediated macrophage ox-LDL uptake in ApoE-/- mice.

  Animalssize not reported3 months

  Hexarelin 100 micrograms/kg s.c. daily versus saline, with normal C57BL/6J controls

  In ApoE-knockout mice on a high-fat diet, 3 months of hexarelin improved blood lipids and reduced atherosclerotic plaque formation.

  Study details

  Studied

  ApoE-/- mice fed a high-lipid diet (plus RAW264.7 macrophages)

  Compared with

  Saline (AS group) and normal controls

  Main outcome

  Atherosclerotic plaque, serum lipids, macrophage ox-LDL uptake, LOX-1 and NF-kB signaling

  Authors' conclusion

  Hexarelin attenuated atherosclerosis in ApoE-/- mice by modulating lipids and inhibiting macrophage ox-LDL uptake via the LOX-1-NF-kB pathway, supporting its potential as an anti-atherosclerotic drug.

  Limitations

  Mouse and cell study.

  DOI 10.1016/j.peptides.2019.170122PubMed 31386895
• ✓ Positive animalMicrovasc Res · 2022

  Hexarelin attenuates abdominal aortic aneurysm formation by inhibiting SMC phenotype switch and inflammasome activation.

  Animalssize not reported

  Hexarelin 200 micrograms/kg twice daily in mice

  In a mouse elastase model, hexarelin reduced abdominal aortic aneurysm diameter, elastin degradation and vascular inflammation.

  Study details

  Studied

  Mouse model of elastase-induced abdominal aortic aneurysm

  Compared with

  Untreated aneurysm mice

  Main outcome

  Infrarenal aortic diameter, elastin degradation, smooth muscle phenotype, inflammasome activation

  Authors' conclusion

  Hexarelin attenuated abdominal aortic aneurysm development in mice by inhibiting smooth muscle cell phenotype switching and NF-kB-mediated inflammation.

  Limitations

  Mouse model only.

  DOI 10.1016/j.mvr.2021.104280PubMed 34856183
• ? Inconclusive reviewJ Geriatr Cardiol · 2014

  The cardiovascular action of hexarelin.

  No new data

  Concise narrative review

  Review of mainly preclinical evidence that hexarelin acts directly on the heart via GHSR and CD36 receptors; presents it as a possible cardiovascular agent without clinical trial evidence.

  Study details

  Main outcome

  Cardiovascular actions of hexarelin

  Authors' conclusion

  Hexarelin acts via GHSR and the CD36 receptor and may have direct cardioprotective actions; it is chemically more stable and potent than ghrelin and may be a promising therapeutic agent for some cardiovascular conditions.

  Limitations

  Narrative review; no new data.

  DOI 10.11909/j.issn.1671-5411.2014.03.007PubMed 25278975Free full text

Reported side effects

• reportedAcute rise in ACTH, cortisol and prolactin after IV dosing [ref]

Longest published human exposure is about 16 weeks in small groups; tolerance (reduced GH response) develops with continued use and long-term safety is unknown.

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.