Compound reference
Sermorelin
Also known as GHRH 1-29, Geref
Sermorelin (GHRH 1-29) is the prototypical GHRH-analogue peptide — once FDA-approved as Geref for pediatric growth-hormone deficiency, withdrawn in 2013 for commercial (not safety) reasons. Today it is sold gray-market for "anti-aging" GH boosting, a use it was never approved or proven for.
- CAS
- 86168-78-7
- Formula
- C₁₄₉H₂₄₆N₄₄O₄₂S
- Molar mass
- ≈3357.9 g/mol
- Sequence
- GHRH(1-29) amide — the first 29 residues of human growth hormone-releasing hormone
- Half-life
- ≈10–20 min (rapid DPP-IV cleavage at the Ala²-Asp³ bond)
Former FDA-approved product; discontinued and not currently marketed as an FDA-approved product in the United States.
Mode of action
Sermorelin is the amidated first 29 amino acids of human growth hormone-releasing hormone — GHRH(1-29) — which is the minimal fragment that retains the full activity of the 44-residue parent hormone. It is a GHRH-receptor agonist: given to the pituitary it stimulates the synthesis and release of growth hormone in the body's own pulsatile pattern, rather than supplying GH directly. Because it works through the intact feedback loop, GH release stays subject to somatostatin restraint, which is part of why GHRH analogues are considered more "physiologic" than exogenous GH.
The trade-off is pharmacokinetic: native GHRH(1-29) is degraded quickly, with a plasma half-life on the order of 10–20 minutes, largely through dipeptidyl peptidase-IV cleavage at the Ala²-Asp³ bond. That short duration shaped both its clinical use (single diagnostic doses, daily bedtime injections) and the later engineering of longer-acting analogues such as tesamorelin and CJC-1295.
Main intended effect
To stimulate the body's own growth-hormone secretion — used historically both as a diagnostic provocative agent and as a therapy to accelerate growth in growth-hormone-deficient children.
Areas of interest
Its established medical interest was pediatric growth-hormone deficiency — both diagnosis and treatment. In the present-day consumer and "wellness" market, sermorelin is promoted off-label as an anti-aging and GH-boosting peptide for adults, frequently through compounding pharmacies, a use distinct from its approved history.
Evidence for intended effects
Sermorelin has real clinical evidence — for its original indications. As a diagnostic agent, intravenous sermorelin at 1 µg/kg reliably provoked GH release in children being evaluated for deficiency. As a therapy, a multicenter Geref International Study Group trial gave 110 growth-hormone-deficient children 30 µg/kg subcutaneously each night for up to a year and documented accelerated growth velocity. On that basis sermorelin acetate was approved by the FDA as Geref.
What that evidence does not cover is the modern selling point. The pediatric-GHD data say nothing about anti-aging, body composition, or performance in healthy adults, where rigorous outcome trials are lacking. So the honest framing is a split between a genuine — if now historical — approved use and a popular contemporary use that rests on extrapolation.
| Strand | What exists | Tier |
|---|---|---|
| Pediatric GHD — diagnosis | Provocative GH-stimulation studies | Established clinical |
| Pediatric GHD — treatment | Multicenter trial; FDA approval (Geref) | Established clinical |
| Adult anti-aging / performance | No rigorous outcome trials | Unproven |
Studied amounts (literature dosing context)
In its clinical use, sermorelin was dosed at 1 µg/kg intravenously for diagnostic GH-stimulation testing, and 30 µg/kg subcutaneously once nightly for treatment of growth-hormone-deficient children. Adult "anti-aging" regimens sold today are not derived from controlled trials. These are historical clinical figures; this page does not provide dosing guidance.
Safety and regulatory status
Sermorelin's regulatory history is unusual and worth stating precisely: it was an FDA-approved drug (Geref, sermorelin acetate, held by Serono), and the FDA's 2013 withdrawal of that approval was made at the applicant's request for commercial reasons — not because of a safety or efficacy finding. It is no longer marketed as an FDA-approved product in the United States. It now reaches users largely through compounding pharmacies and the research-peptide gray market for unapproved adult uses, where product identity and purity are not assured. It sits in the same GHRH-analogue family as tesamorelin (still approved, for a specific indication) and CJC-1295 (a longer-acting research analogue).
Sources
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
Multicenter open-label trial (Thorner et al., Geref International Study Group) of 110 previously untreated prepubertal growth-hormone-deficient children given sermorelin (GHRH 1-29) 30 micrograms/kg subcutaneously once daily at bedtime for up to one year, with 86 completing efficacy analysis. Height velocity rose from a baseline of 4.1 +/- 0.9 cm/yr to 8.0 +/- 1.5 cm/yr at 6 months and 7.2 +/- 1.3 cm/yr at 12 months, with 74% of children classified as good responders at 6 months and bone-age advancement proportional to height-age progression. Treatment was well tolerated, with stable glucose and appropriate IGF-1 generation. As an open-label single-arm design over one year, it does not establish final adult height or provide a concurrent somatropin comparator.
Testing with growth hormone-releasing factor (GRF(1-29)NH2) and somatomedin C measurements for the evaluation of growth hormone deficiency
Diagnostic-utility study (Ranke et al.) evaluating intravenous GRF(1-29)NH2 (sermorelin) at 1 microgram/kg in 131 children and adolescents (45 with idiopathic growth hormone deficiency, 86 without), measuring peak GH over a 120-minute window alongside somatomedin C. Using a normal threshold of peak GH above 10 ng/mL, 11 of 45 GHD cases exceeded it (false negatives) while 3 of 86 non-GHD subjects fell below it (false positives), indicating that a normal GHRH response cannot exclude hypothalamic-origin deficiency. The authors conclude GRF testing alone has insufficient stand-alone sensitivity and specificity and that confirmatory provocative testing is often needed. This is a diagnostic accuracy evaluation, not a treatment trial.
Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency
Review (Prakash and Goa) of sermorelin, a synthetic 29-amino-acid GHRH analogue, across diagnostic and therapeutic pediatric use. For diagnosis, intravenous sermorelin 1 microgram/kg rapidly stimulates GH with relatively few false positives versus other provocative tests, though a normal response does not exclude hypothalamic deficiency and combination with arginine may improve specificity. For treatment, once-daily subcutaneous sermorelin 30 micrograms/kg at bedtime produced sustained height-velocity increases over 12 months (with limited data to 36 months), but the gains were smaller than with once-daily somatropin. Tolerability was good, with transient facial flushing and injection-site pain the main adverse events; the effect on final adult height remained undetermined at publication.
Catabolism of rat growth hormone-releasing factor(1-29) amide in rat serum and liver
Preclinical metabolism study (Boulanger, Roughly, Gaudreau) characterizing degradation of synthetic rat GRF(1-29)NH2 in rat serum and liver homogenate by HPLC. Apparent half-lives were short — 18 +/- 4 min in serum and 13 +/- 3 min in liver homogenate — with the Ala2-Asp3 bond (a DPP-IV site) cleaved in both tissues, trypsin-like cleavage at Arg11-Arg12 and Arg20-Lys21 in serum, and chymotrypsin-like cleavage at Tyr10-Arg11 and Tyr18-Ala19 in liver, yielding fragments such as rGRF(1-20)OH and rGRF(1-18)OH. The data explain the rapid clearance and short duration of action of GRF(1-29) and motivate protease-resistant analog design. Findings are in rat tissue and use the rat GRF sequence, so direct quantitative extrapolation to human pharmacokinetics is constrained.
Determination of Withdrawal of Approval for GEREF (Sermorelin Acetate) Injection — Federal Register Notice
FDA Federal Register determination on GEREF (sermorelin acetate) injection, covering NDA 19-863 and NDA 20-443 held by Serono, which carried diagnostic and treatment indications for idiopathic growth hormone deficiency in children. The notice records that the applicant requested withdrawal for commercial reasons, and FDA explicitly determined the product was not withdrawn from sale for reasons of safety or effectiveness. That determination clears the regulatory pathway for abbreviated new drug applications (ANDAs) referencing GEREF. This is the authoritative regulatory record of sermorelin's prior FDA-approved status and its administrative withdrawal; it documents marketing status, not new clinical evidence.
https://www.govinfo.gov/content/pkg/FR-2013-03-04/pdf/2013-04827.pdf