Educational reference only. Informational material drawn from peer-reviewed literature. Not medical advice and not a recommendation to use, dose, or modify any therapy. Decisions about hormone therapy should be made with a qualified healthcare provider.
Overview
Overview
Hexarelin is a synthetic hexapeptide that functions as a potent growth hormone secretagogue receptor (GHS-R1a) agonist and the most potent GH-releasing peptide in the GHRP class. It is structurally and functionally related to GHRP-6 (essentially a methylated derivative) but produces greater peak GH release than any other GHRP at equivalent doses, approximately 1.5–2 fold higher than ipamorelin at equimolar doses.
However, this superior GH-releasing potency comes with substantial trade-offs: significant cortisol and prolactin elevation, pronounced tachyphylaxis (desensitization), and the most off-target effects of the major GHRPs except possibly GHRP-6.
Hexarelin's defining clinical feature beyond GH stimulation is its cardiovascular activity. Like GHRP-6, hexarelin binds both GHS-R1a and the CD36 scavenger receptor, with CD36 binding underlying cardioprotective effects that appear substantially independent of GH release. Multiple animal studies have demonstrated improvements in left ventricular function in ischemic heart failure models, increased stroke volume, cardiac output, and cardiac index, and protection against ischemia/reperfusion injury. These cardioprotective effects occur even in GH-deficient models, confirming the GH-independent mechanism.
Forms
Available forms & half-lives
| Form | Approximate half-life |
|---|---|
| Intravenous hexarelin | ~70 minutes |
| Subcutaneous hexarelin | ~55 minutes |
| Intranasal hexarelin | Variable, lower bioavailability (~5%) |
| Oral hexarelin | <1% bioavailability; not practical |
What it does
Main effects
- Most potent GH-releasing peptide of the GHRP class: approximately 1.5–2× higher peak GH levels than ipamorelin at equimolar doses; IV ED50 ~0.48 mcg/kg vs ~0.7–1.0 mcg/kg for GHRP-6
- Dual GHS-R1a + CD36 receptor binding: the D-2-methyl-tryptophan at position 2 (vs D-tryptophan in GHRP-6) provides enhanced metabolic stability and increased receptor binding affinity
- GH pulses with rapid onset: peak GH 50–80 µg/L at 1–2 µg/kg IV, peak response at 30 minutes (Ghigo et al. 1994)
- Significant cardiovascular research: CD36-mediated cardioprotection in ischemic heart failure models; improvements in left ventricular function, stroke volume, cardiac output, cardiac index; protection against ischemia/reperfusion injury via IL-1 signaling pathway PMID: 28321024
- Cardiovascular effects are substantially independent of GH release: confirmed in GH-deficient models; mediated by CD36 binding in cardiac tissue PMID: 10465272
- Multiple administration routes characterized: SC bioavailability ~77%, intranasal ~5%, oral <1% (Ghigo et al. 1994)
- Separate pathway from GHRH analogs: GHRH receptor and GHS-R1a signaling reach pituitary somatotrophs through different receptors
- Historical use as a GH stimulation test in some clinical contexts, leveraging its high potency
What to watch for
Common side effects
- Pronounced tachyphylaxis is the major practical limitation: significant desensitization develops within 4 weeks of continuous use, more pronounced than ipamorelin or GHRP-2 tachyphylaxis
- Significant cortisol elevation (+40–80%): among the highest of the major GHRPs; clinical implications include weight gain with chronic use, mood lability, glucose dysregulation, immunosuppression, possible bone density effects, adrenal axis effects; cortisol profile similar to human corticotropin-releasing hormone (hCRH)
- Significant prolactin elevation (+80%): highest of the major GHRPs; possible galactorrhea, gynecomastia in men, sexual dysfunction, fertility effects, water retention
- Injection site reactions (pain, redness, swelling): mild
- Mild constitutional symptoms (flushing common with initial doses, headache common, tingling/numbness in extremities, drowsiness)
- Moderate appetite stimulation: less than GHRP-6 but more than ipamorelin
- Insulin resistance with chronic use: combined GH + cortisol effects; more significant than ipamorelin; caution in diabetic patients
- IGF-1 elevation with chronic use: monitoring recommended; tachyphylaxis may limit sustained elevation
- Water retention: common; related to prolactin and GH/IGF-1 effects
- Phase 2 development discontinued: no regulatory approval anywhere
- Quality concerns for research chemical supply (identity, concentration, sterility)
- WADA-prohibited under category S2
Key facts
Key facts worth knowing
- Hexarelin is a synthetic hexapeptide with sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂ (MW 887.04 Da). The D-2-methyl-tryptophan at position 2 is the key structural modification distinguishing it from GHRP-6 (which has D-tryptophan at this position). This methylation provides enhanced metabolic stability and increased receptor binding affinity.
- Most potent GH-releasing peptide of the GHRP class. Produces approximately 1.5–2× higher peak GH levels than ipamorelin at equimolar doses. The IV ED50 is approximately 0.48 mcg/kg vs ~0.7–1.0 mcg/kg for GHRP-6.
- Pronounced tachyphylaxis is the major practical limitation. Significant desensitization develops within 4 weeks of continuous use. This is more pronounced than tachyphylaxis with ipamorelin or GHRP-2.
- Significant cortisol and prolactin elevation. Cortisol elevation of +40–80% above baseline and prolactin elevation of +80% have been documented, both substantially higher than with ipamorelin or GHRP-2. The cortisol elevation profile is similar to that of human corticotropin-releasing hormone (hCRH). PMID: 9437229
- Significant cardiovascular research. Demonstrated cardioprotective effects in ischemic heart failure models including ischemia/reperfusion injury models, with mechanisms including IL-1 signaling pathway modulation, CD36 receptor activation, and PKC pathway engagement. PMID: 28321024
- Phase 2 clinical development was conducted for various indications but discontinued. No regulatory approval anywhere. Used historically as a GH stimulation test in some clinical contexts.
- WADA Prohibited under category S2.
Legal status
Legal status
No FDA approval. No regulatory approval anywhere. Phase 2 development discontinued for all GH-axis indications. Some compounding pharmacies supply it, with evolving regulatory status. Not a controlled substance. WADA-prohibited under category S2.