Sermorelin is a synthetic peptide made of the first 29 amino acids of human growth hormone-releasing hormone (GHRH), the hypothalamic hormone that stimulates growth hormone release from the pituitary gland. It is the shortest piece of GHRH that keeps the full biological activity of the 44-residue hormone[1]. Under the brand name Geref it was approved in the United States as a diagnostic test in 1990 and as a treatment for children with growth hormone deficiency in 1997[2].
The manufacturer stopped making Geref in 2008, and the FDA later confirmed that it was not withdrawn for reasons of safety or effectiveness[2]. Today sermorelin is better known as an "anti-ageing" peptide. Evidence for that use comes mainly from small, short studies in older men. Some hormonal and functional measures improved, but these uncontrolled studies did not establish lasting health benefits or effects on ageing[3][4].
| Also known as | GHRH(1-29)-NH2, GRF(1-29)NH2; brand Geref |
|---|---|
| Sequence | Residues 1–29 of human GHRH, C-terminal amide |
| Molecular weight | 3357.9 Da (calculated, free base) |
| Half-life in blood | About 6 minutes after intravenous injection |
| Approved uses (US) | Diagnostic test (1990); growth hormone deficiency in children (1997) |
| Status | Discontinued in 2008; the FDA determined the withdrawal was not for safety or effectiveness reasons |
| Sport | Prohibited by WADA (class S2, GHRH analogues) |
What the molecule is
Natural GHRH has 44 amino acids, but its activity sits in the front part of the chain. The fragment 1–29 with an amide at the C-terminus binds the same receptor and produces the full effect, which makes it the shortest fully active form[1]. Sermorelin carries no other modifications. This sets it apart from tesamorelin, which keeps all 44 residues and adds a trans-3-hexenoyl group to the N-terminus to slow its breakdown.
Why it lasts only minutes
In human plasma, GHRH and its short forms are cut at the bond between residues 2 and 3. A 1989 study showed that a single enzyme does this, dipeptidyl peptidase-4 (DPP-4), which removes the first two amino acids, tyrosine and alanine, in one step. A specific DPP-4 inhibitor blocked the cut, and so did replacing the alanine at position 2 with its D-isomer, which the enzyme does not recognise[6]. In the 1–29 fragment a second, trypsin-like enzyme also cuts after lysine 12[6]. After 60 minutes in human plasma, 94% of GHRH(1-29)-NH2 had been degraded[6].
In a study in healthy volunteers given sermorelin into a vein, cited in the same review, the half-life was 6.1 minutes, and the peptide could no longer be detected after 15 to 20 minutes[1]. The 1989 study already tested analogues designed to resist DPP-4[6], and the N-terminal cap of tesamorelin serves the same purpose.
Use as a medicine
As a diagnostic test. A single intravenous dose of 1 µg per kg body weight tests whether the pituitary can release growth hormone. According to a 1999 review of the trials, in normally growing children it gave false "deficient" results less often than other stimulation tests: in up to 14.9% of children, against 23.2 to 49.1% with other agents. But a normal result cannot rule out a deficiency that starts in the hypothalamus rather than the pituitary, and 24.4% of children already diagnosed by conventional tests responded normally to sermorelin[1].
As a treatment. The main evidence for treatment came from one multicentre, open-label study without a control group. It enrolled 110 previously untreated prepubertal children with growth hormone deficiency, of whom 86 were eligible for the efficacy analysis. The children injected 30 µg per kg of sermorelin under the skin every evening for up to a year[7]. Their growth rate rose from 4.1 cm per year before treatment to 8.0 cm per year after 6 months and 7.2 cm per year after 12 months. At 6 months, 74% of the children grew at least 2 cm per year faster than before treatment[7].
The approved dose was never compared directly with growth hormone injections. In two smaller randomised studies that used other sermorelin regimens, children on daily growth hormone grew faster[1]:
| Study and treatment | Sermorelin | GH |
|---|---|---|
| Chen 1993, continuous pump | 9.2–9.3 | 14.6 |
| Neyzi 1993, 3 injections a day | 7.9–10.3 | 12.4 |
GH, growth hormone (somatropin) 30 µg/kg once daily. Ranges for sermorelin cover the two doses tested, 30 and 60 µg/kg a day. Data as summarised by Prakash and Goa (1999)[1].
Sermorelin only works if the pituitary itself is intact, and children who did not respond could switch to growth hormone[1]. Its effect on final adult height was never established[1].
Why it left the market
EMD Serono discontinued the diagnostic form of Geref in July 2008 and the treatment form in December 2008, and asked the FDA to withdraw both approvals. The FDA did so in 2009[2].
In 2012 a citizen petition asked the FDA whether Geref had been withdrawn for safety or effectiveness reasons. The agency reviewed its files, the literature and post-marketing adverse event data, and in 2013 concluded that it had not. Geref stays on the FDA's list of discontinued drug products, which means a generic version could in principle be approved if it met the other requirements[2]. The notice does not say why the company stopped making the drug[2].
Side effects
The most common reaction to an intravenous test dose was brief facial flushing, reported in 20 to 30% of children[1]. In the year-long treatment study, local reactions at the injection site such as pain, swelling or redness occurred in 16 of 110 children, and 2 stopped treatment because of side effects, one with hives and one with general malaise[1][7]. Fasting glucose did not change, and IGF-1 did not rise excessively[7].
Most treated children developed antibodies against GHRH: 20% after 3 months, 54% after 6 months and 62% after 12 months of daily injections, and nearly all children treated by continuous pump. The antibodies were not linked to a weaker effect or to more side effects, and their titres fell after treatment stopped[1]. Hypothyroidism was reported in up to 6.5% of patients in clinical trials, a rate similar to that seen with growth hormone itself[1]. Long-term safety data in large numbers of patients were never collected[1].
Studies in older men
Growth hormone and IGF-1 fall with age, and in the 1990s researchers tested whether sermorelin could restore them. Two small studies from the US National Institute on Aging are the ones most often cited:
- Corpas et al. (1992). Ten healthy men aged about 68 injected sermorelin twice a day for 14 days at each of two doses, 0.5 mg and 1 mg. At the higher dose their growth hormone release and IGF-1 rose to the levels measured in nine young men; at the lower dose the changes were not significant. There was no placebo group[3].
- Vittone et al. (1997). Eleven men aged 64 to 76 with low IGF-1 injected 2 mg every night for 6 weeks. Night-time growth hormone release rose, but IGF-1 did not change. Two of six strength tests and one endurance test improved; body weight, muscle and fat measured by DEXA, glucose and lipids did not change. There was no control group, and the authors concluded that a single nightly dose was less effective than several doses a day[4].
These studies demonstrate short-term effects on growth hormone secretion but do not establish meaningful improvements in body composition, long-term health or ageing. Longer studies with modified GHRH analogues exist, but their results cannot be transferred to sermorelin itself.
Sermorelin is prohibited in sport at all times. WADA names it among GHRH analogues in class S2, together with tesamorelin and CJC-1295[8].
In short
- Sermorelin is residues 1–29 of human GHRH with a C-terminal amide, the shortest fully active form of the hormone.
- Plasma enzymes, mainly DPP-4, cut it within minutes; its half-life after intravenous injection is about 6 minutes.
- As Geref it was approved in the US as a diagnostic test (1990) and for children with growth hormone deficiency (1997), with the main evidence for treatment from one uncontrolled study.
- The manufacturer stopped making it in 2008; the FDA found this was not for safety or efficacy reasons.
- Studies in older men were small, short and uncontrolled; they showed hormonal changes and some functional improvements, but did not establish lasting health benefits.
References
- Prakash A, Goa KL (1999). Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs 12(2):139–157. DOI: 10.2165/00063030-199912020-00007
- U.S. Food and Drug Administration (2013). Determination that GEREF (sermorelin acetate) injection, 0.5 milligrams base/vial and 1.0 milligrams base/vial, and GEREF (sermorelin acetate) injection, 0.05 milligrams base/amp, were not withdrawn from sale for reasons of safety or effectiveness. Federal Register 78(42):14095–14096. govinfo.gov
- Corpas E, Harman SM, Piñeyro MA, Roberson R, Blackman MR (1992). Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. Journal of Clinical Endocrinology & Metabolism 75(2):530–535. DOI: 10.1210/jcem.75.2.1379256
- Vittone J, Blackman MR, Busby-Whitehead J, Tsiao C, Stewart KJ, Tobin J, Stevens T, Bellantoni MF, Rogers MA, Baumann G, Roth J, Harman SM, Spencer RGS (1997). Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism 46(1):89–96. DOI: 10.1016/S0026-0495(97)90174-8
- U.S. Food and Drug Administration (2025). EGRIFTA WR (tesamorelin) for injection, for subcutaneous use: full prescribing information, section 11. accessdata.fda.gov (PDF)
- Frohman LA, Downs TR, Heimer EP, Felix AM (1989). Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma. Journal of Clinical Investigation 83(5):1533–1540. DOI: 10.1172/JCI114049
- Thorner M, Rochiccioli P, Colle M, Lanes R, Grunt J, Galazka A, Landy H, Engrand P, Shah S, on behalf of the Geref International Study Group (1996). Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. Journal of Clinical Endocrinology & Metabolism 81(3):1189–1196. DOI: 10.1210/jcem.81.3.8772599
- World Anti-Doping Agency (2025). The 2026 Prohibited List, International Standard. wada-ama.org