Sermorelin
Also known as GHRH (1-29), GRF 1-29, Sermorelin acetate, Geref, Geref Diagnostic
The active 1-29 fragment of GHRH; once FDA-approved, withdrawn in 2008 for commercial reasons.
At a glance
- Category
- Growth hormone
- Status
- research chemical
- Route
- subcutaneous (intravenous for the diagnostic application)
- Half-life
- approximately 11-12 minutes (human, intravenous); several tens of minutes subcutaneously
- Onset
- GH peak within 15-30 minutes; effect on height growth or body composition only after months
- Molecular weight
- 3357.9 g/mol
- 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 (YADAIFTNSYRKVLGQLSARKLLQDIMSR-NH2)
Was approved in the US as two separate EMD Serono products: Geref injection 0.5 and 1.0 mg base/vial (NDA 20-443, approved 26 September 1997) for idiopathic growth hormone deficiency in children with growth failure, and Geref injection 0.05 mg base/amp (NDA 19-863, approved 28 December 1990) for evaluating the ability of the pituitary somatotroph to secrete growth hormone 3. EMD Serono notified the FDA in 2008 that both were being discontinued and requested withdrawal of the applications; the FDA withdrew approval of both NDAs effective 18 June 2009, and in a 2013 notice determined that neither product had been withdrawn from sale for reasons of safety or effectiveness 3. There is now no registered product; in the US it is available only as a compounding pharmacy preparation, and it is not registered in the EU.
Doping status: Prohibited at all times (WADA S2, GH-releasing factors)
Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.
Mechanism of action
Sermorelin is a synthetic copy of the first 29 amino acids of human growth hormone-releasing hormone (GHRH 1-44). This fragment carries the full biological activity of the complete hormone. It binds to the GHRH receptor on the somatotroph cells of the anterior pituitary, activates the cAMP/PKA pathway and stimulates both the production and the release of growth hormone.
As a GHRH analogue, sermorelin differs fundamentally from the ghrelin receptor agonists (ipamorelin, hexarelin, GHRP-2, GHRP-6, MK-677): these act on the GHS-R1a receptor. Both classes raise GH, but via separate signalling pathways that reinforce each other. Combined administration of a GHRH analogue and a GHRP therefore produces a GH response greater than the sum of the two — the reason the two classes are in practice almost always used together.
Sermorelin preserves negative feedback: as IGF-1 rises and somatostatin tone increases, the response is damped. This makes acromegaly-like overdosing practically unlikely, unlike with exogenous growth hormone. The flip side is that the response depends entirely on a functioning pituitary: in pituitary GH deficiency sermorelin does not work, only in hypothalamic deficiency.
The very short half-life (approximately 11-12 minutes, through breakdown by dipeptidyl peptidase-4) is the reason later analogues were developed in which that breakdown is blocked: mod GRF 1-29 (four substitutions), CJC-1295 with DAC (substitutions plus albumin binding) and tesamorelin (a hexenoyl group on the complete GHRH 1-44).
What the research shows
Sermorelin is one of the few agents in this category with genuine clinical registration data: it was shown in controlled research to be effective in growth hormone deficiency in children and was suitable as a diagnostic for pituitary function. The evidence for its current use — anti-ageing and body composition purposes in healthy adults — is by contrast thin and largely absent.
Research in humans
Studies in children with growth hormone deficiency showed accelerated height growth with daily subcutaneous administration, although the effect was smaller than with recombinant growth hormone. The 1993 Acta Paediatrica study was randomised, allocating 60 children to two GHRH(1-29) doses or to growth hormone for six months 2; the larger 1996 JCEM study, 110 previously untreated children treated for up to a year, was open-label and had no control group 1, which is worth noting because it is the more frequently quoted of the two. The diagnostic application as a pituitary stimulation test has been extensively validated. For healthy adults there are small, largely uncontrolled studies showing a rise in GH and IGF-1; randomised research into muscle mass, fat mass, sleep or wellbeing in healthy adults is almost entirely absent.
Animal and lab research
Amply documented in animal studies: sermorelin produces dose-dependent GH release and promotes growth in young animals. These data are mainly of historical value, because human registration data exist.
Caveats. The best evidence concerns a population (GH-deficient children) and an endpoint (height growth) that say nothing about use by healthy adults. The agent was withdrawn from the market not because of failure but for commercial reasons, as a result of which research largely came to a halt after 2008. What is traded as sermorelin via compounding or grey channels is not subject to registration control on purity and content.
What it is used for
- Historical: treatment of idiopathic growth hormone deficiency in children with growth failure — the approved indication of Geref injection 0.5 and 1.0 mg base/vial 3
- Historical: evaluating the ability of the pituitary somatotroph to secrete growth hormone — the approved indication of Geref injection 0.05 mg base/amp 3
- Current, off-registration: raising one's own GH and IGF-1 release in adults, often in combination with a GHRP
- Prescribed in American anti-ageing clinics for sleep, recovery and body composition — indications for which no randomised evidence exists
Dosing
- Only the paediatric dose (0.03 mg/kg) and the diagnostic dose (1 mcg/kg) come from the product information registered at the time; the paediatric figure matches the 30 mcg/kg per day given subcutaneously at bedtime in the 1996 multicentre trial 1. Adult doses come from compounding practice and user protocols and have never been established in controlled research.
- Administration before sleep aligns with the natural nocturnal GH peak.
- Administration on an empty stomach: raised insulin and free fatty acids blunt the GH response.
- Because of the very short half-life, the effect depends strongly on the timing of administration; this makes sermorelin more demanding to use than the stabilised analogues.
- Sermorelin only works with a functioning pituitary; in pituitary GH deficiency it is by definition without effect.
These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.
Protocols
Geref in growth hormone-deficient children, 1996 multicentre trial
published trialSource: Journal of Clinical Endocrinology & Metabolism, 1996
| Once daily at bedtime | 30 mcg/kg subcutaneously |
|---|---|
| Duration | up to 1 year |
An open-label trial in 110 previously untreated prepubertal GH-deficient children, of whom 86 were eligible for the efficacy analysis. Sermorelin acts on the pituitary, so it only works where the pituitary can still respond; in pituitary GH deficiency it is by definition ineffective, which is part of why it lost out to recombinant GH.
Sermorelin, circulating adult schedule
user protocol — not validatedSource: Pattern reported by compounding clinics and on forums
This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.
| Before bed, on an empty stomach | 200-500 mcg subcutaneously |
|---|---|
| Frequency | once daily; some schedules add a second morning dose |
| Run length | 3-6 months |
The half-life is a matter of minutes, so this schedule stands or falls on timing: taken after a meal, with insulin and free fatty acids raised, the same dose produces markedly less GH release. The registered product was withdrawn in 2008 for commercial reasons, so what is used now is compounded or grey-market material, and no adult dose was ever established in controlled research.
Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.
Reconstitution
- Vial sizes
- 0.5 mg, 1 mg (historical Geref vials), 5 mg, 9 mg (compounding)
- Solvent
- bacteriostatic water (0.9% benzyl alcohol); the registered product used sterile or bacteriostatic water
- Storage
- Reconstituted 2-8 °C, keeps for approximately 2-4 weeks. Powder refrigerated or in the freezer, protected from light.
Worked example
5 mg vial + 2.5 ml bacteriostatic water = 2 mg/ml. 300 mcg = 0.15 ml = 15 units on a U100 insulin syringe.
Let the water run down the wall of the vial; do not shake. Sermorelin is less stable in solution than the modified analogues (mod GRF 1-29, CJC-1295), so its shelf life after reconstitution is shorter.
Work it out for Sermorelin
Safety
Side effects
- Redness, pain or swelling at the injection site — the most frequently reported side effect in the registration studies
- Flushing, a sensation of warmth in the face and headache shortly after injection
- Nausea, vomiting and an unpleasant taste in the mouth (especially after intravenous administration for the diagnostic test)
- Fluid retention and oedema in the hands and ankles with more prolonged use
- Tingling or numbness in the hands; carpal tunnel syndrome is a class effect of raised GH
- Joint and muscle pain
- Reduced insulin sensitivity and raised fasting glucose with more prolonged use
- Dizziness, drowsiness, restlessness
- Formation of anti-GHRH antibodies was described in the paediatric studies; in the 1996 multicentre trial GHRH(1-29) was overall well tolerated, with no adverse changes in general biochemical or hormonal analyses, no excessive IGF-1 generation and no change in fasting glucose over up to a year of treatment 1
Do not use if
- Active or previously treated malignancy — GH and IGF-1 are growth factors and the concern that they may stimulate existing malignant cells is theoretical but has not been refuted
- Hypersensitivity to sermorelin or benzyl alcohol
- Diabetes mellitus or impaired glucose tolerance without medical supervision
- Active diabetic retinopathy
- Pregnancy and breastfeeding
- Severe acute illness, after open heart surgery or in acute respiratory failure
- Untreated hypothyroidism — this blunts the GH response and must be treated first
- Untreated pituitary disorder or pituitary adenoma
Interactions
Glucocorticoids suppress the GH response to sermorelin — this was already included in the Geref product information. Somatostatin analogues (octreotide, lanreotide), H1-type antihistamines, atropine and muscarinic antagonists blunt or block the response; these agents had to be stopped before the diagnostic test. Untreated hypothyroidism and obesity also lower the response. Levodopa and clonidine increase GH release and can distort the result. Raised GH and IGF-1 reduce insulin sensitivity and may increase the need for antidiabetic medication.
Common questions
What is sermorelin?
What is the difference between sermorelin and CJC-1295?
Is sermorelin used with ipamorelin?
Is sermorelin legal or banned in sport?
Sources
- Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapyJournal of Clinical Endocrinology & Metabolism, 1996
- A comparative study of growth hormone (GH) and GH-releasing hormone(1-29)-NH2 for stimulation of growth in children with GH deficiencyActa Paediatrica Supplement, 1993
- Determination That GEREF (Sermorelin Acetate) Injection Was Not Withdrawn From Sale for Reasons of Safety or EffectivenessFederal Register, FDA, 2013