August 1, 2026 · 3 min read

Hexarelin: a synthetic GH secretagogue and the cardiac findings

A look at hexarelin, a peptidyl growth hormone secretagogue: where its receptors are, GH responses in people, repeated exposure and cardiac studies.

Hexarelin is a synthetic six-amino-acid peptide that binds the growth hormone secretagogue (GHS) receptor, the receptor that ghrelin activates. It was developed as a growth hormone (GH) releasing agent, and later papers found that it also acts on heart tissue. This note sorts out which findings concern the pituitary and which concern the heart.

The hexarelin sequence

Positively charged
Modified residue
Hydrophobic

Length: 6 amino acids
Average mass: 887.0 Da
Formula: C47H58N12O6

His-2-methyl-D-Trp-Ala-Trp-D-Phe-Lys-NH2. A synthetic peptide with no natural precursor, so the structure comes from PubChem (CID 6918297). The mass calculated from it matches PubChem.

Where the receptors are

A 2000 survey of human tissues found GHS receptors mainly in the heart, and also in many other tissues. In endocrine tissues, hexarelin, the small-molecule secretagogue MK-0677 and human ghrelin all displaced the radioligand, with MK-0677 and ghrelin less potent than hexarelin. In nonendocrine tissues only hexarelin displaced it. The authors suggested that a receptor subtype specific to peptidyl secretagogues may exist in the heart and elsewhere.

GHS binding sites in human tissue

Highest binding
Myocardium.
Then, in decreasing order
Adrenal, gonads, arteries, lung, liver, skeletal muscle, kidney, pituitary, thyroid, adipose tissue, veins, uterus, skin and lymph node.
Negligible binding
Parathyroid, pancreas, placenta, mammary gland, prostate, salivary gland, stomach, colon and spleen.

From Papotti et al., J Clin Endocrinol Metab 2000, using a radioreceptor assay with a labeled hexarelin analogue on human tissue samples.

Growth hormone release in people

A 2001 study compared ghrelin, hexarelin and GHRH-29 in seven healthy men. Hexarelin raised GH well above GHRH, and ghrelin raised it more than hexarelin (P < 0.05). The authors also note that hexarelin stimulates prolactin, ACTH and cortisol secretion in addition to GH, so its hormonal footprint is wider than GH alone.

Peak GH after three stimuli

GHRH-2926.7 µg/L
Hexarelin68.4 µg/L
Ghrelin92.1 µg/L

Mean peak GH in seven healthy young men given each agent intravenously on separate occasions, from Arvat et al., J Clin Endocrinol Metab 2001.

Repeated exposure

Earlier work had suggested that continuous exposure to GH-releasing peptides desensitizes the GH response. A 1996 study asked what happens with intermittent exposure in healthy older people. Seven elderly subjects received hexarelin intranasally for 8 days, and seven elderly women received it orally for 15 days. In both studies the GH response was maintained rather than blunted. IGFBP-3 rose in both, IGF-I rose slightly with the oral treatment, prolactin and cortisol did not change, and no side effects were reported.

The heart

A 1999 study in seven men with GH deficiency and nine controls found that hexarelin raised left ventricular ejection fraction (LVEF) in both groups without changing catecholamine levels, blood pressure or cardiac output. The GH response in the deficient men was negligible, so the authors read the effect as a short-lasting positive inotropic effect that is probably independent of GH and mediated by myocardial receptors.

A 2002 study then looked at patients with severe left ventricular dysfunction. GH rose similarly in both groups. LVEF rose in the five patients with ischemic cardiomyopathy but not in the eight with dilated cardiomyopathy. The authors proposed that the effect in the ischemic group reflects direct stimulation of viable myocardium or contractile reserve.

Left ventricular ejection fraction before and at peak after hexarelin

Before hexarelin
Peak after hexarelin

Healthy controls

63% Before hexarelin
70% Peak after hexarelin

GH deficiency

50% Before hexarelin
57% Peak after hexarelin

Ischemic cardiomyopathy

22.6% Before hexarelin
26.2% Peak after hexarelin

Dilated cardiomyopathy

16.7% Before hexarelin
17.7% Peak after hexarelin

Single intravenous administration. Healthy controls (n = 9) and GH deficiency (n = 7) from Bisi et al., Eur J Pharmacol 1999. Ischemic (n = 5) and dilated (n = 8) cardiomyopathy from Imazio et al., Eur J Heart Fail 2002.

Reading these results

A 2018 review in Sexual Medicine Reviews notes that GH secretagogues promote pulsatile GH release that stays subject to negative feedback, but that few long-term, rigorously controlled studies exist. It flags a concern about blood glucose through reduced insulin sensitivity, and calls for long-term safety work, including cancer incidence and mortality.

The cardiac studies are acute. They measured ejection fraction after a single administration, in groups of five to nine people.
Hormone and imaging measures are not clinical outcomes. None of these papers shows a health benefit.
Hexarelin is less selective than a pure GH signal, because it also raises prolactin, ACTH and cortisol.

The calculated average mass is about 887 Da, but mass alone cannot tell D-amino acids from L-amino acids. A certificate of analysis for a peptide with two D residues should say how the structure was confirmed.