Compounds / GH secretagogues

Hexarelin

Hexarelin (Examorelin): His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2

Synthetic hexapeptide GHSR-1a agonist developed by Mediolanum Pharmaceuticals in the 1990s. Most potent GHRP for raw GH-release magnitude per dose, but produces the largest cortisol/prolactin elevations of any GHRP and is uniquely prone to rapid receptor desensitization (tachyphylaxis). Practical use requires short cycles (≤4 wk) followed by 4-8 wk washout. Reached Phase 3 trials but never gained marketing approval.

At a glance

Half-life

~54 min ~50-55 minutes plasma t½. Peak GH 15-30 min post-injection, decays over ~2h.

Routes

SubQ

Vial sizes

2 mg · 5 mg

Evidence base

4 studies 3 human · 1 preclinical

Mechanism

Dual-receptor agonist: (1) GHSR-1a on pituitary somatotrophs and hypothalamic AgRP/NPY neurons (canonical GH-releasing pathway, shared with all GHRPs) and (2) CD36 on cardiomyocytes and microvascular endothelium: molecular basis for hexarelin's cardiovascular action. HPA-axis activation via hypothalamic AVP release rather than CRH explains the larger cortisol/prolactin spike. GHSR-1a desensitizes rapidly: second dose 60 min after first showed significantly attenuated GH response (first demonstration of acute tachyphylaxis); 16-week chronic dosing reduces GH AUC by ~45%, recovers within 4 weeks of washout. CD36 activation produces dose-dependent coronary vasoconstriction; absent in CD36-knockout mice. Foundational dose-response across multiple routes established in healthy human volunteers.

Dosing

Published evidence

1. Human RCT 1998

   Growth hormone status during long-term hexarelin therapy

   Rahim A, O'Neill PA, Shalet SM J Clin Endocrinol Metab

   16-week SC hexarelin in healthy elderly. GH AUC declined from 19.1 → 10.5 by wk 16; recovered to 19.4 by wk 20. IGF-1, IGFBP-3, body fat, lean mass, BMD all UNCHANGED at wk 16. Demonstrates chronic hexarelin produces minimal biological impact despite acute desensitization. Foundational paper for the 'short cycle' practice.

   PMID 9589671

2. Human RCT 1996

   The effect of repeated administration of hexarelin and GHRH on growth hormone responsivity

   Massoud AF, Hindmarsh PC, Matthews DR, Brook CG Clin Endocrinol

   n=6 healthy adult males. Hexarelin alone produced larger GH response than GHRH; combined produced supra-additive synergy. CRITICAL: second hexarelin bolus 60 min after first showed significantly attenuated GH response: first demonstration of acute tachyphylaxis at GHSR-1a.

   PMID 8762732

3. Human RCT 1994

   Growth hormone-releasing activity of hexarelin in humans: a dose-response study

   Imbimbo BP, Mant T, Edwards M, et al. Eur J Clin Pharmacol

   Foundational dose-response paper for hexarelin in healthy human volunteers across multiple routes (oral, intranasal, IV, SC). Established GH-release potency profile.

   PMID 7957536

4. Animal in vivo 2002

   CD36 mediates the cardiovascular action of GHRPs in the heart

   Bodart V, Febbraio M, Demers A, et al. Circ Res

   Identifies CD36 (84 kDa scavenger receptor on cardiomyocytes/microvascular endothelium) as the cardiac receptor for hexarelin. Activation produces dose-dependent coronary vasoconstriction; absent in CD36-knockout mice.

   PMID 11988484

Reported side effects

Cortisol elevation

Very common Moderate · ~40% increase at 0.5 mcg/kg dose. LARGEST cortisol response of any GHRP. Mediated via hypothalamic AVP release. Chronic use may contribute to elevated baseline cortisol.

Prolactin elevation

Very common Mild · ~80% increase per dose. Larger than ipamorelin or GHRP-2. May affect libido/fertility with chronic supratherapeutic use.

GH receptor desensitization (tachyphylaxis)

Very common Moderate · Defining limitation. Second dose 60 min after first produces significantly attenuated GH response. 16-wk chronic use ↓ GH AUC ~45%. Reversible within 4 wk washout.

Hunger / appetite increase

Common Mild · Less pronounced than GHRP-6 but more than ipamorelin. Ghrelin-receptor mediated.

Flushing / warmth

Occasional Mild · Transient post-injection.

Water retention

Occasional Mild · GH-mediated.

Coronary vasoconstriction (theoretical)

Rare Serious · In animal/perfused-heart studies, hexarelin at high dose produces dose-dependent coronary vasoconstriction via CD36 (Bodart 2002). Clinical relevance at standard human SC doses unclear, but worth flagging for users with CAD or hypercholesterolemia.

Interactions

• CJC-1295 (no DAC) Synergy

  GHRH+GHRP supra-additive GH pulse via independent receptor pathways.

• Ipamorelin Redundant

  Both GHSR-1a agonists; stacking compounds desensitization.

• GHRP-2 Redundant

  Same receptor target.

• GHRP-6 Redundant

  Same receptor; both spike cortisol/prolactin.

• MK-677 Redundant

  All GHSR-1a agonists.

• Corticosteroids Caution

  Hexarelin elevates endogenous cortisol; adding exogenous glucocorticoids amplifies HPA-axis impact.

Reconstitution and storage

5 mg vial + 2 mL BAC water = 2.5 mg/mL = 250 mcg per 10 units on insulin syringe. Gentle swirl, do not shake.

Lyophilized: freezer (-20°C). Reconstituted: refrigerate 2-8°C, use within 30-45 days. Protect from light.

Open the reconstitution calculator for Hexarelin