Sermorelin
Sermorelin is the amidated 29-amino-acid N-terminal fragment of human growth hormone-releasing hormone, and is the shortest synthetic GHRH peptide that retains the full biological activity of the native hormone. Given intravenously or subcutaneously it stimulates growth hormone secretion from the anterior pituitary. It was developed as a prescription medicine — sermorelin acetate, marketed as Geref by Serono — for provocative testing and for treatment of childhood idiopathic growth hormone deficiency, and the trial literature dates almost entirely from that era. It is now discussed in the sports-medicine literature among peptides sold direct to patients outside formal regulatory approval, and the administration of GHRH and its synthetic analogues is prohibited in sport by the World Anti-Doping Agency.
Information on this page is provided for laboratory research reference. The compound is not a drug, supplement, or medical product, and is not for human or veterinary use, ingestion, or consumption.
No reviewed report has been published for this product family yet. The molecular values opposite are public reference data, not results measured on a CRX sample.
Browse published reports →Sermorelin acts at the GHRH receptor, a class B G-protein-coupled receptor expressed on anterior-pituitary somatotrophs, where receptor engagement drives both growth hormone gene expression and release of stored hormone. Because the peptide stimulates the pituitary rather than substituting for growth hormone, secretion is described as preserving physiological growth hormone release and remains subject to somatostatin and IGF-I feedback — the stated rationale for GHRH-based approaches over exogenous growth hormone. That rationale is only partly borne out: in the University of Washington older-adult work a single evening injection produced one large post-injection burst without restoring nighttime pulsatile secretion, and late-night secretion fell below baseline. Whether the downstream limb of the axis is engaged depends on schedule and analogue — hepatic IGF-I and IGFBP-3 rose on twice-daily dosing at the higher dose and on a nightly GHRH analogue, but did not move at all on a single nightly 2 mg GHRH(1-29) injection over six weeks. The requirement for residual somatotroph reserve is a hard constraint rather than a theoretical one: in the pediatric trials roughly a quarter to a third of children did not respond usefully. Whether GHRH receptors outside the pituitary mediate additional tissue effects was an open question in the receptor literature and remains proposed rather than established.2,5,6,7,8
Class B G-protein-coupled receptor on anterior-pituitary somatotrophs; the receptor through which GHRH stimulates growth hormone synthesis and secretion. An inactivating Ghrhr mutation produces growth hormone deficiency and a dwarf phenotype in the little mouse — a mouse model, with the corresponding search for inactivating human GHRHR mutations described as ongoing at the time of the review.5
The proximate output. Sermorelin amplifies endogenous secretory pulses rather than replacing the hormone, so effect size tracks residual pituitary reserve; in growth-hormone-deficient children 26% were not classed as good responders at 6 months in the 110-child study and 31.3% were classed as poor responders in the 16-child Venezuelan study.7,9,10
Downstream mediators of most systemic growth hormone effects. IGF-I rose in old men only on the higher (1 mg) twice-daily GHRH-(1-29) dose and not on 0.5 mg; IGF-I and IGFBP-3 both rose within 2 weeks on a nightly 10 microgram/kg [Nle27]GHRH-(1-29)-NH2 analogue before returning toward baseline by 16 weeks; and neither changed on a single nightly 2 mg GHRH(1-29) injection over six weeks. Schedule and analogue therefore determine whether this limb is engaged.7,8,11
Proposed, not established. The receptor literature flagged the possibility of additional receptors mediating extrapituitary GHRH actions as an open research question.5
Growth hormone axis
In a randomised 6-month trial in 60 children with growth hormone deficiency of hypothalamic origin, mean height velocity reached 9.2 and 9.3 cm/yr on the 30 and 60 microgram/kg/day GHRH(1-29)-NH2 arms versus 14.6 cm/yr on recombinant growth hormone (p < 0.01 for growth hormone versus either GHRH arm). Serum IGF-I rose initially on GHRH, then fell back to near pretreatment values.12
In an uncontrolled open-label multicentre study of 110 previously untreated prepubertal children with growth hormone deficiency — of whom 86 were eligible for the efficacy analysis — subcutaneous GHRH(1-29) raised mean height velocity from 4.1 +/- 0.9 cm/yr at baseline to 8.0 +/- 1.5 cm/yr at 6 months and 7.2 +/- 1.3 cm/yr at 12 months, with 74% classed as good responders at 6 months. There was no placebo or active comparator arm.9
In 10 healthy old men (68.0 +/- 6.2 years), 14 days of twice-daily GHRH-(1-29) at the 1 mg dose raised mean 24-hour growth hormone (p < 0.001) and IGF-I (p < 0.005) above the men's own basal values, to levels that no longer differed from 9 untreated young men (26.2 +/- 4.1 years); the 0.5 mg dose did not reach significance. There was no placebo arm.7
In an uncontrolled, open-label before-and-after study in 11 healthy men aged 64 to 76 with low baseline IGF-I, 6 weeks of a single nightly 2 mg GHRH(1-29) injection raised mean nocturnal growth hormone release above each man's own baseline (p < 0.02) but left IGF-I, IGFBP-3, weight, body mass index, DEXA fat and muscle, lipids and glucose tolerance unchanged. Only 2 of 6 strength measures improved. There was no placebo group.8
In a review of the pediatric literature, the growth hormone response to a single intravenous sermorelin challenge was characterised as a rapid and relatively specific provocative test, producing false-positive responses in fewer children without growth hormone deficiency than other provocative tests; a normal response could not exclude growth hormone deficiency of hypothalamic origin and had to be read alongside a subnormal response to another test.1
Metabolic & weight
Across two placebo-controlled studies of a single evening GHRH(1-29)NH2 injection in healthy older adults, the investigators reported preliminary, incomplete results: IGF-I rose about 40% in men and about 30% in women not on estrogen but under 10% in estrogen-replaced women, and percentage body fat fell about 5% with a reciprocal lean-mass gain in men and non-estrogen-replaced women. Strength and aerobic fitness did not improve in the 6-month arm.2,6
In a single-blind randomised trial in 19 adults aged 55-71 whose only control was a 4-week within-subject saline run-in, 16 weeks of nightly [Nle27]GHRH-(1-29)-NH2 — the norleucine-27 analogue of sermorelin, not sermorelin itself — increased skin thickness in both sexes (p < 0.05) and lean body mass in men only (p < 0.05), with no change in bone mineral density, weight or blood pressure. IGF-I and IGFBP-3 rose within 2 weeks, remained elevated for 12 weeks and returned toward baseline by 16 weeks.11
What investigators recorded alongside the results above, at the rates their papers state.
Anti-GHRH antibody formation12
All 20 children on the 60 microgram/kg/day arm and 19 of 20 on the 30 microgram/kg/day arm developed GHRH antibodies over 6 months; titres showed no correlation with height gain and had almost disappeared 9 months after treatment stopped. No growth hormone antibodies were detected.
Transient facial flushing and injection-site pain1
Reported as the most common adverse events across single intravenous and repeated once-daily subcutaneous sermorelin studies; the review characterised both routes as well tolerated without giving pooled rates.
Transient hyperlipidaemia11
Described as the only adverse side effect in 19 adults aged 55-71 over 16 weeks of the norleucine-27 GHRH(1-29) analogue; it resolved by the end of the study. Fasting insulin and glucose were unaltered.
Worsened subjective sleep quality2,6
Pittsburgh Sleep Quality Index total rose from 4.1 +/- 2.8 to 5.41 +/- 2.8 in 37 GHRH-treated participants (p < 0.05) versus no change in 38 placebo participants (4.51 +/- 2.9 to 4.61 +/- 2.7). These are preliminary data from an incomplete trial and no individual PSQI component showed a clear treatment effect. A later review from the same group described GHRH as failing to improve and possibly impairing deep sleep in this trial.
No adverse biochemical or metabolic changes detected over 12 months of pediatric dosing9
In 110 children treated for up to 1 year in an uncontrolled open-label study, no adverse changes in general biochemical or hormonal analyses were noted, with no change in fasting glucose concentration and no excessive generation of IGF-I. Absence of a control arm limits what this establishes.
Absence of contemporary human safety data for direct-to-patient use1,3
Not quantified. A 2026 sports-medicine narrative review placed sermorelin among peptides marketed direct to patients and stated that for unapproved peptides in this gray market rigorous human safety data are scarce and there is potential for serious harm; the published sermorelin safety record comes almost entirely from prescription-era trials conducted between 1987 and 2006.
- 1.Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. · BioDrugs · 1999 · PMID 18031173
- 2.Treating age-related changes in somatotrophic hormones, sleep, and cognition. · Dialogues in Clinical Neuroscience · 2001 · PMID 22034239
- 3.Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance. · Sports Medicine · 2026 · PMID 41966639
- 4.Advances in the detection of growth hormone releasing hormone synthetic analogs. · Drug Testing and Analysis · 2021 · PMID 34665524
- 5.The growth-hormone-releasing hormone receptor: signal transduction, gene expression, and physiological function in growth regulation. · Annals of the New York Academy of Sciences · 1996 · PMID 8993403
- 6.Growth hormone (GH)-releasing hormone and GH secretagogues in normal aging: Fountain of Youth or Pool of Tantalus? · Clinical Interventions in Aging · 2008 · PMID 18488883
- 7.Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. · The Journal of Clinical Endocrinology and Metabolism · 1992 · PMID 1379256
- 8.Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. · Metabolism: Clinical and Experimental · 1997 · PMID 9005976
- 9.Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. Geref International Study Group. · The Journal of Clinical Endocrinology and Metabolism · 1996 · PMID 8772599
- 10.Long-term therapy with a single daily subcutaneous dose of growth hormone releasing hormone (1-29) in prepubertal growth hormone deficient children. Venezuelan Collaborative Study Group. · Journal of Pediatric Endocrinology · 1994 · PMID 7735367
- 11.Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. · The Journal of Clinical Endocrinology and Metabolism · 1997 · PMID 9141536
- 12.A comparative study of growth hormone (GH) and GH-releasing hormone(1-29)-NH2 for stimulation of growth in children with GH deficiency. · Acta Paediatrica. Supplement · 1993 · PMID 8329830
- 13.Effects of growth hormone–releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. · Archives of Neurology · 2012 · PMID 22869065