B tier · viable
It is the only compound here besides tesamorelin with a genuine FDA approval history and a published registration dataset showing a hard growth outcome in children, but the product was withdrawn and the adult anti-ageing trials are small and largely negative.
sermorelin
Sermorelin is the shortest fully active fragment of human GHRH and acts as a GHRH-receptor agonist on pituitary somatotrophs. It held FDA approval as Geref for paediatric growth hormone deficiency and as a diagnostic agent for pituitary function before both approvals were withdrawn in 2009 following commercial discontinuation.
// we supply this one
available as a research reagent
≥ 98% HPLC · lyophilised powder · batch certificate published. Grade B above is our own and is not adjusted because we stock it.
the explanation
Sermorelin is the first 29 building blocks of the natural hormone that tells the pituitary to release growth hormone, which is all the body needs for the signal to work. It was a real approved medicine for short children in the 1990s, then the manufacturer stopped selling it and the approval lapsed, which is not the same as it being pulled for being unsafe.
regulatory status
Formerly FDA-approved, withdrawn from sale
Approved as Geref (NDA 19-863 in 1990 for diagnostic use; NDA 20-443 in 1997 for paediatric GHD), discontinued in 2008 and approvals withdrawn effective 18 June 2009, with FDA formally determining in 2013 that the withdrawal was not for reasons of safety or effectiveness.
how it works · proposed mechanism
Sermorelin is native GHRH truncated to its minimum functional length.
The active 29-residue core
Full-length human GHRH is 44 amino acids, but biological activity resides in residues 1-29. Sermorelin reproduces that core with a C-terminal amide and binds the same pituitary GHRH receptor.
Requires a working pituitary
Because sermorelin only asks the pituitary to release GH it already made, it produces no response where somatotroph reserve is absent. This is why it was approved as a diagnostic provocative test as well as a treatment.
Degraded within minutes
Dipeptidyl peptidase-4 cleaves the N-terminal dipeptide almost immediately, giving an 11-12 minute half-life. Subcutaneous bioavailability is only about 6%, so most of an injected dose never reaches the pituitary intact.
Antibodies are common
The Geref label reports that a large proportion of treated children developed anti-GRF antibodies at least once during therapy. The label states this did not appear to alter growth response, but it is an unresolved immunogenicity finding.
what’s reported
evidence shape
6 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
The registration data are open-label growth-velocity data in children, with only 56 of 110 enrolled patients evaluable at 12 months, and the observed response was smaller than what recombinant GH achieves in the same population. In adults the controlled trials are tiny and mostly null: Vittone 1997 found no change in IGF-1, weight or DEXA body composition after six weeks of nightly dosing in 11 elderly men.
key published findings
- Human registration study (Geref label): 110 children with idiopathic growth hormone deficiency received sermorelin 0.03 mg/kg/day subcutaneously; among 56 evaluable at 12 months, growth velocity rose from 4.1 ± 1.0 cm/yr at baseline to 8.0 ± 1.5 cm/yr at 6 months and 7.2 ± 1.3 cm/yr at 12 months, a mean increase of 3.1 ± 1.4 cm/yr (p = 0.0001).
- Human RCT (Vittone, Metabolism 1997, n=11): six weeks of nightly 2 mg subcutaneous GHRH(1-29) in healthy men aged 64-76 with low baseline IGF-1 produced no significant change in IGF-1, weight, BMI, waist-hip ratio or DEXA muscle and fat, with only 2 of 6 strength measures improving.
- Human RCT (Khorram, JCEM 1997, n=19): 16 weeks of nightly 10 µg/kg of the sermorelin analogue [Nle27]GHRH(1-29)NH2 in adults aged 55-71 raised IGF-1 within 2 weeks and increased skin thickness in both sexes, but lean body mass rose only in men and fat mass did not change.
- Human RCT (Chen, Acta Paediatr Suppl 1993, n=60): children with hypothalamic growth hormone deficiency randomised across three arms comparing GH with GHRH(1-29)-NH2 for growth stimulation.
- Regulatory pharmacokinetics (Geref label): elimination half-life 11-12 minutes after either intravenous or subcutaneous administration, with mean absolute subcutaneous bioavailability of about 6%.
limitations of the evidence
- The pivotal paediatric dataset is open-label growth velocity with substantial attrition, not a placebo-controlled trial with a final-height endpoint.
- Adult and anti-ageing use has never been tested in an adequately powered controlled trial; the existing adult studies enrolled 11-19 subjects and used analogues rather than sermorelin itself in one case.
- Immunogenicity was common in the registration programme and its long-term consequences were never characterised, since the product was discontinued before post-marketing follow-up matured.
identity
| full name | human growth hormone-releasing hormone (1-29) amide |
| category | Growth Hormone |
| modality | peptide |
| formula | C149H246N44O42S |
| molar mass | 3357.89 g/mol |
| cas | 86168-78-7 |
| half-life | ~11-12 min (IV or SC; Geref label) |
| sequence | Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2 |
laboratory handling
| storage | Lyophilised sermorelin acetate is stored desiccated at -20°C or below for long-term laboratory storage and protected from light; the marketed Geref vials were labelled for refrigerated storage at 2-8°C. Reconstituted solution is held at 2-8°C and is not intended for extended storage. |
| solubility | Readily soluble in sterile or bacteriostatic water; the marketed product was reconstituted with bacteriostatic water for injection, and laboratory stocks are commonly prepared in water or dilute aqueous buffer. |
| co-studied with | Sermorelin is a GHRH-receptor agonist and is frequently co-studied with GHS-R1a agonists on the classical Bowers rationale that GHRH and GHRP act through separate receptors and produce more than additive GH release, though no controlled trial of a sermorelin-plus-GHRP combination has been published. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedFederal Register (U.S. Food and Drug Administration) · 2013 · official
EMD Serono / U.S. Food and Drug Administration · 1997 · official
Metabolism: Clinical and Experimental · 1997 · peer-reviewed
Journal of Clinical Endocrinology & Metabolism · 1997 · peer-reviewed
Acta Paediatrica Supplement · 1993 · peer-reviewed
others in Growth Hormone