Sermorelin
Growth Hormone-Releasing Hormone (1-29) amide · GRF 1-29 · GHRH (1-29) · Sermorelin acetate · Geref
The first 29 amino acids of human GHRH, once approved as Geref and now compounded.
Typical dose
300 mcg
once nightly, 5-7 nights per week
Range
100–500
mcg
Half-life
12 min
see Dosing
Evidence
Human trials
Subcutaneous
What it is
Sermorelin is the shortest fragment of human growth hormone-releasing hormone that retains full biological activity — residues 1 through 29 of the native 44-amino-acid hormone, with an amidated C-terminus. Everything past residue 29 turns out to be dispensable for receptor binding, which is why every GHRH analogue on the market is built on this fragment.
It is one of only two GHRH analogues ever approved by the FDA — tesamorelin is the other — and the only one ever approved for growth hormone deficiency. Sold as Geref, it was approved for treating growth hormone deficiency in children and as Geref Diagnostic for pituitary function testing, then withdrawn from the US market in 2008 for commercial reasons rather than safety findings. It is now supplied by compounding pharmacies and by research-chemical vendors.
Its weakness is pharmacokinetic, not pharmacological. Unmodified GRF(1-29) is a substrate for DPP-4, which removes the N-terminal Tyr-Ala dipeptide and inactivates it within about ten minutes. Mod GRF 1-29 and tesamorelin both exist specifically to fix that, which is why sermorelin has largely been displaced in bodybuilding use despite being the better-documented molecule.
How it works
Sermorelin binds the GHRH receptor on pituitary somatotrophs, activating adenylate cyclase and the cAMP/PKA pathway, which drives both synthesis and release of stored growth hormone. Because the pituitary is the effector, the response is self-limiting: somatostatin tone and IGF-1 feedback both cap how much GH any single dose can produce, and the axis cannot be pushed past its own capacity the way it can with injected recombinant GH.
DPP-4 in plasma clips it apart quickly, so a dose produces one sharp pulse lasting well under an hour. That short action is why it is dosed at night — the injection lands on the body's own first slow-wave-sleep GH pulse and amplifies it rather than adding an unnatural daytime one.
Dosing
Geref's paediatric label dose was 30 mcg/kg nightly — far higher than the 100-500 mcg flat doses adult clinics use — so the common protocol is conservative relative to the approved product, not aggressive.
Reconstitution calculator
Pre-loaded with Sermorelin’s vial size, water volume and typical dose. Change anything.
Typical: 300 mcg · range 100–500
Draw to
30 u
0.3 mL · 300 mcg
Concentration
1 mg/mL
10 mcg per unit
Doses per vial
6.7
Vial lasts
7 days
CheckThe draw fills more than 90% of the barrel. Workable, but there is no room for an air bubble or a correction.
Once mixed
Refrigerated at 2-8C and used within 2-4 weeks; sermorelin is one of the less stable GHRH peptides in solution, so do not stretch a vial for months.
Direct the bacteriostatic water against the vial wall and let it run down onto the powder, then roll the vial between your palms until it clears — do not shake. A 2 mg vial in 2 mL gives 1000 mcg/mL, so 300 mcg is 0.3 mL, or 30 units on a U-100 insulin syringe.
Storage
Before mixing
Sealed and dry at 2-8C for up to about two years, or -20C indefinitely; keep it dark.
After mixing
Refrigerated at 2-8C and used within 2-4 weeks; sermorelin is one of the less stable GHRH peptides in solution, so do not stretch a vial for months.
Reported benefits
- ▪The best-documented GHRH analogue, with published paediatric efficacy and diagnostic use
- ▪GH release stays under normal feedback control, so overshoot is largely self-limiting
- ▪Very short action means a mistimed or oversized dose clears within the hour
- ▪Reported improvements in sleep depth and next-day recovery
- ▪Works well paired with a GHRP, which suppresses the somatostatin brake
- ▪Available on prescription from compounding pharmacies in many markets
Side effects
- ▪Flushing and a warm head-rush in the first minutes after injection
- ▪Injection-site pain, redness or swelling — the most common complaint in trials
- ▪Headache and transient dizziness
- ▪Mild fluid retention and hand tingling at higher nightly doses
- ▪Reduced insulin sensitivity and higher fasting glucose over a multi-month course
- ▪Nausea, altered taste or a metallic taste shortly after dosing
- ▪Vivid dreams or fragmented sleep if the dose is too large
- ▪Antibody formation was seen in a minority of paediatric patients on long-term use
Do not use if
- ▪Active or suspected malignancy — GH and IGF-1 are trophic to existing tumours
- ▪Pregnancy and breastfeeding
- ▪Known pituitary tumour, or prior pituitary surgery or cranial irradiation
- ▪Untreated hypothyroidism, which blunts the GH response and should be corrected first
- ▪Poorly controlled diabetes
Evidence level — Human trials
Controlled human clinical data exists.
Formerly FDA-approved as Geref and withdrawn from the US market in 2008; now supplied by compounding pharmacies on prescription or sold as a research chemical.
Commonly run with
Ipamorelin
The selective GHRP: a clean GH pulse with almost no cortisol, prolactin or hunger.
300 mcg · 1-3x daily
GHRP-2
Potent, well-studied GHRP with a bigger pulse than ipamorelin and more cortisol.
100 mcg · 2-3x daily
GHRP-6
The original GHRP: solid GH release and the strongest hunger response of the group.
100 mcg · 2-3x daily
Hexarelin
The most potent GHRP, and the fastest to stop working if you run it continuously.
100 mcg · 1-2x daily
Sermorelin FAQ
Sermorelin or Mod GRF 1-29 — is there a real difference?+
Mod GRF 1-29 is sermorelin with four substitutions that block DPP-4, taking the half-life from about ten minutes to about thirty. In practice Mod GRF gives a larger, longer pulse per microgram. Sermorelin's advantage is that it is the molecule with actual human trial and approval history behind it.
Why is it always dosed at night?+
The largest natural GH pulse of the day comes shortly after sleep onset during slow-wave sleep. A short-acting GHRH analogue given at bedtime amplifies that existing pulse instead of creating a separate daytime one, and daytime insulin from meals blunts the response anyway.
Will it show up on a drug test?+
GHRH analogues including sermorelin are on the WADA prohibited list at all times, and dedicated assays exist for GHRH-analogue detection in tested sport. It is not detected by standard anabolic-steroid panels, but assuming it is invisible to a serious anti-doping programme is a mistake.
How long until anything is measurable?+
GH rises within 15-30 minutes of a single dose, but IGF-1 — the marker worth tracking — moves over weeks, not days. Most protocols retest IGF-1 at six to eight weeks. If it has not moved at all by then, the likely explanations are an inadequate dose, degraded peptide, or a pituitary that is not responding.
Does it lose effect over time?+
Pituitary responsiveness to GHRH does not crash the way it does with continuous stimulation, and paediatric patients were treated for months to years. Users commonly report subjective effects tapering after a few months, which is why 3-6 month blocks with a break are the usual pattern rather than open-ended use.
References
- 1.Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency — BioDrugs (1999) PMID 18031173
- 2.Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? — Clin Interv Aging (2006) PMID 18046908
- 3.Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma — J Clin Invest (1989) PMID 2565342
More gh secretagogues
CJC-1295 no-DAC
Short-acting GHRH fragment that sharpens one GH pulse, almost always run with a GHRP.
100 mcg · 1-3x daily
CJC-1295 with DAC
Albumin-binding GHRH analogue that lifts GH and IGF-1 for days from one injection.
1000 mcg · 1-2x weekly
GHRP-2
Potent, well-studied GHRP with a bigger pulse than ipamorelin and more cortisol.
100 mcg · 2-3x daily
GHRP-6
The original GHRP: solid GH release and the strongest hunger response of the group.
100 mcg · 2-3x daily