Hexarelin Side Effects: Cortisol, Prolactin, Desensitization, and Cardiac Research

Hexarelin's side effects in human studies are mainly endocrine: it raises ACTH, cortisol and prolactin along with growth hormone, it reduced deep sleep in a small overnight study, and its GH response partially fades with repeated use. It also acts on the heart, where it increased left ventricular ejection fraction in small acute studies and binds the scavenger receptor CD36. All of this comes from small, short human studies run in the 1990s and early 2000s; there are no large or long-term safety trials.

This guide lists each effect, the evidence behind it, and the contraindication and monitoring questions for prescribers.

Educational content for licensed healthcare professionals. Not medical advice; dosing and treatment decisions belong to the prescribing clinician.

What Hexarelin Is

Hexarelin is a synthetic six-amino-acid growth hormone releasing peptide (GHRP) that activates the ghrelin receptor (GHS-R1a) in the pituitary and hypothalamus. It belongs to the same class as GHRP-2, GHRP-6 and ipamorelin, and in human work it was a stronger GH stimulus than GHRH or GHRP-6 [2]. It differs from ipamorelin in one clinically relevant way: it is not selective. In human studies it stimulated ACTH, cortisol and prolactin as well as GH [1]. For background, see the Hexarelin library page.

Hexarelin Side Effects: Evidence Table

Endocrine Effects: ACTH, Cortisol and Prolactin

The most consistent hexarelin finding outside GH is activation of the stress and lactotroph axes. A study comparing ghrelin, hexarelin and GHRH in healthy young men described hexarelin as a strong GH releaser that also significantly stimulates prolactin, ACTH and cortisol; natural ghrelin produced even larger rises in all three [1]. In a placebo-controlled sleep study of seven young men, repeated evening administration significantly increased GH and prolactin across the night and ACTH and cortisol during the first half of the night [2]. In an acute cardiac study, hexarelin, but not recombinant GH, significantly increased cortisol [6].

Repeated exposure changes the pattern. In six healthy young men given hexarelin across a day, a later challenge showed a blunted GH response and an abolished ACTH and cortisol response, while the prolactin rise was unchanged [3]. Prolactin therefore appears to be the endocrine effect least affected by repeated use.

These effects matter clinically for patients with conditions sensitive to cortisol or prolactin, and they are the main reason more selective secretagogues were developed.

Sleep Changes

In the same sleep study, hexarelin decreased stage 4 sleep in the first half of the night and EEG delta power across the whole night. The authors proposed that the drug shifts the balance from GHRH toward CRH activity, which impairs deep sleep [2]. This contrasts with ghrelin and GHRH, which promote slow-wave sleep. The study was small and single-night, but it is the only direct human sleep data for hexarelin.

Desensitization

Two human studies show that the GH response weakens with continued use:

• Healthy elderly adults (n = 12, 16 weeks). The GH area under the curve fell significantly by weeks 4 and 16. Four weeks after stopping, it returned to baseline, so the attenuation was partial and reversible [4].
• Short prepubertal children (n = 7, 6–10 months). Peak GH responses fell within a week and stayed lower, yet growth velocity still increased; responsiveness recovered three months after stopping [5].

Desensitization is not dangerous in itself, but it limits the long-term usefulness of the drug and complicates interpretation of IGF-1 trends.

Cardiac Effects and CD36

Hexarelin has cardiac actions separate from GH. In seven healthy men, it increased left ventricular ejection fraction within 15 minutes, peaking at 30 minutes and lasting about an hour, without changes in blood pressure or heart rate; recombinant GH at matched GH levels did not [6]. In patients with severe left ventricular dysfunction, it raised ejection fraction in ischemic but not dilated cardiomyopathy [7].

The likely receptor is CD36. In rat hearts, a hexarelin derivative bound CD36 on cardiomyocytes and endothelial cells, and hexarelin raised coronary perfusion pressure, a vasoconstrictive effect absent in CD36-deficient hearts. The authors suggested CD36 may mediate coronary vasospasm in hypercholesterolemia and atherosclerosis [8]. The human significance is unknown, but it is a reason for caution in patients with coronary disease.

Who Should Avoid Hexarelin

• Active or prior malignancy, as with any agent that raises GH and IGF-1.

• Hyperprolactinemia, prolactinoma, or pituitary disease, given the consistent prolactin rise.
• Cushing syndrome, poorly controlled diabetes, or other cortisol-sensitive conditions.
• Coronary artery disease or significant cardiomyopathy, given the CD36 and inotropic findings.
• Pregnancy and breastfeeding, for which there are no data.
• Competitive athletes. Non-approved substances fall within WADA's prohibited categories.

Monitoring Considerations for Prescribers

• Baseline and follow-up IGF-1, interpreted with desensitization in mind.
• Prolactin, especially if galactorrhea, menstrual change or libido change appears.
• Morning cortisol or clinical review for cortisol-excess symptoms in at-risk patients.
• Fasting glucose and HbA1c, as with any GH-raising therapy.
• Sleep quality, given the slow-wave sleep finding.
• Cardiac history, with a low threshold for cardiology input in known coronary disease.

Regulatory Status (October 2026)

Hexarelin is not an FDA-approved drug and is not on the 503A Bulks List. It is not among the substances our FDA Peptide Status Tracker lists as under evaluation or scheduled for a PCAC meeting. Confirm current compounding eligibility with the partner pharmacy before prescribing.

Frequently Asked Questions

What are the most common side effects of hexarelin?

In human studies, the consistent findings are increases in cortisol, ACTH and prolactin alongside GH. One small study also found reduced deep sleep. Large trials that would capture common everyday complaints have not been done.

Does hexarelin raise cortisol and prolactin?

Yes. Several human studies show rises in ACTH, cortisol and prolactin. With repeated exposure, the cortisol response was abolished while the prolactin rise persisted.

Does hexarelin stop working over time?

The GH response partially declines with continued use. In a 16-week study of older adults, the response fell significantly but returned to baseline four weeks after stopping.

Is hexarelin bad for the heart?

The human data show a short-lived increase in ejection fraction, not harm. However, hexarelin binds CD36 and caused coronary vasoconstriction in rat hearts, so patients with coronary disease warrant caution.

How does hexarelin compare with ipamorelin for side effects?

Ipamorelin was introduced as the first selective GH secretagogue: in swine it released GH without the ACTH and cortisol rises seen with GHRP-2 and GHRP-6 [9]. Hexarelin raised ACTH, cortisol and prolactin in humans. See our Ipamorelin page for its profile.

Newtropin does not prescribe, compound, or dispense. We connect licensed providers with licensed 503A compounding partners; prescribers can start at For Providers.

References

1. Arvat E, et al. Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone. J Clin Endocrinol Metab. 2001;86(3):1169-74. PubMed
2. Frieboes RM, et al. Hexarelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers. Psychoneuroendocrinology. 2004;29(7):851-60. PubMed
3. Maccario M, et al. 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. Eur J Endocrinol. 2002;146(3):310-8. PubMed
4. Rahim A, et al. Does desensitization to hexarelin occur? Growth Horm IGF Res. 1998;8 Suppl B:141-3. PubMed
5. Klinger B, et al. Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormone-releasing peptide in short children. Eur J Endocrinol. 1996;134(6):716-9. PubMed
6. Bisi G, et al. Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans. J Endocrinol Invest. 1999;22(4):266-72. PubMed
7. Imazio M, et al. GH-independent cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to dilated and ischemic cardiomyopathy. Eur J Heart Fail. 2002;4(2):185-91. PubMed
8. Bodart V, et al. CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Circ Res. 2002;90(8):844-9. PubMed
9. Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-61. PubMed