Peptides & growth hormone

Sermorelin

Updated · 21 sources · Editorial policy

Sermorelin is a synthetic copy of the first 29 amino acids of growth hormone-releasing hormone (GHRH), the hypothalamic hormone that signals the pituitary gland to release growth hormone (GH). Unlike CJC-1295 no DAC, Mod GRF 1-29 and CJC-1295 with DAC, which are built on the same fragment, sermorelin carries no amino acid substitutions: it is the natural fragment, made synthetically (Esposito et al., Adv Drug Deliv Rev 2003).

It is also the only member of that family that was ever an approved medicine. Serono’s Geref was approved by FDA in 1990 as a diagnostic test of pituitary GH secretion and in 1997 as a treatment for children with idiopathic GH deficiency. Both products were discontinued in 2008 and their approvals were withdrawn in 2009, and FDA later determined that this was not for reasons of safety or effectiveness (Federal Register, 2013). Its human evidence comes almost entirely from children with GH deficiency; there are no controlled trials of sermorelin for body composition or performance in healthy adults.

This page summarizes what the regulatory record, pediatric trials and small adult studies report. It is for education only and is not medical advice.

Property Detail
Class Synthetic GHRH analog; the unmodified, amidated GHRH(1-29) fragment
Other names GRF 1-29, GHRH 1-29, sermorelin acetate, Geref
Former brand Geref (EMD Serono): NDA 019863 (diagnostic, approved 1990) and NDA 020443 (treatment, approved 1997)
Former indications Diagnostic test of pituitary GH secretion; idiopathic GH deficiency in children with growth failure
Route and studied doses Intravenous 1 µg/kg as a diagnostic test; subcutaneous 30 µg/kg once daily at bedtime in pediatric trials
Half-life About 10–20 minutes in human plasma; disappearance half-time 4.3 minutes during an infusion study
Molecular formula C₁₄₉H₂₄₆N₄₄O₄₂S, molecular weight 3357.9 g/mol (PubChem)
US status No FDA-approved product on the market (discontinued 2008); not a controlled substance
WADA status Prohibited at all times under S2.2.4 (named as an example)

What it is

Structure

Natural human GHRH is 44 amino acids long. Its first 29 amino acids, with the end of the chain capped as an amide, keep the hormone’s activity in laboratory tests and are almost equally effective at triggering GH release in the body. Sermorelin is that 29-amino-acid fragment, with a composition identical to the start of the natural hormone (Esposito et al., 2003). A drug review described it as the shortest synthetic peptide with the full biological activity of GHRH (Prakash and Goa, BioDrugs 1999). PubChem lists its formula as C₁₄₉H₂₄₆N₄₄O₄₂S with a molecular weight of 3357.9 g/mol (PubChem). The drug was supplied as the acetate salt.

Because sermorelin is the unaltered natural sequence, it also has the natural fragment’s weak points. The blood enzyme dipeptidyl peptidase IV (DPP-IV) cuts off the first two amino acids, leaving a product with less than a thousandth of the original activity (Frohman et al., J Clin Invest 1986). The kidneys also filter the small peptide out quickly (Esposito et al., 2003). Every later analog in the table below was designed to fix one or both of these problems.

Sermorelin and its relatives

Peptide Change from sermorelin Human data Status
Sermorelin None; the natural GHRH(1-29) fragment Pediatric trials; small adult studies FDA-approved as Geref; discontinued 2008
GHRH(1-29) with D-alanine at position 2 One substitution that blocks the DPP-IV cut Clearance study in 10 men Never approved
Mod GRF 1-29, also sold as CJC-1295 no DAC Four substitutions that block enzyme cleavage, slow chemical breakdown and strengthen receptor binding None published Never approved
CJC-1295 with DAC The same four substitutions plus an albumin-binding group Early-phase studies in healthy adults; half-life 5.8–8.1 days Never approved
Tesamorelin Full 44-amino-acid GHRH with a hexenoyl group added at the start of the chain Randomized trials FDA-approved as Egrifta (2010)

Sources for the table: Soule et al., JCEM 1994; Jetté et al., Endocrinology 2005; Teichman et al., JCEM 2006; Dominikowski et al., Front Endocrinol 2026; Drugs@FDA, Egrifta. The Mod GRF 1-29 page explains each of the four substitutions in detail.

The practical consequence: sermorelin is the only peptide in this group with a regulatory record, and the trial data on sermorelin cannot be transferred to its modified relatives, nor theirs to it.

How it works in the body

Sermorelin binds GHRH receptors on the pituitary cells that make GH (somatotrophs) and triggers GH release. GH in turn drives the liver to make IGF-I (insulin-like growth factor I). Because it acts upstream of GH, its effect stays subject to the body’s normal brakes, such as somatostatin and IGF-I feedback (Dominikowski et al., 2026). This is the main difference from injecting growth hormone itself, and also why a normal response requires a working pituitary.

The peptide is very short-lived, but the GH release it triggers lasts longer:

Measure Finding Setting
Plasma half-life About 10–20 minutes, mainly from kidney filtration and enzyme cleavage Humans (Esposito et al., 2003)
Disappearance half-time 4.3 minutes (vs 6.7 minutes for the D-alanine-2 analog) Constant IV infusion, 10 healthy men (Soule et al., 1994)
Metabolic clearance 39.7 mL/kg/min (vs 21 mL/kg/min for the D-alanine-2 analog) Same study
GH response to IV dose Detectable at 0.25 µg/kg; maximal at 1–2 µg/kg; GH elevated for about 3 hours 30 healthy men (Wilton et al., Acta Paediatr Suppl 1993)
Nasal absorption Bioavailability 3–5% Same study

Former approved medical use

FDA approved two Geref products, both held by EMD Serono (Federal Register, 2013):

Product Application Approved Indication
Geref injection, 0.05 mg/ampule NDA 019863 December 28, 1990 Evaluating the ability of the pituitary somatotrophs to secrete GH
Geref injection, 0.5 mg and 1.0 mg vials NDA 020443 September 26, 1997 Idiopathic GH deficiency in children with growth failure

As a diagnostic test, a single intravenous dose of 1 µg/kg was used alongside conventional GH stimulation tests. A normal GH response could not rule out GH deficiency caused by a problem in the hypothalamus, because the drug bypasses the hypothalamus and acts directly on the pituitary (Prakash and Goa, 1999). For treatment, the dose studied in the pivotal trial was 30 µg/kg once daily by subcutaneous injection at bedtime (Thorner et al., JCEM 1996).

Discontinuation

EMD Serono notified FDA in July 2008 that the diagnostic product was being discontinued and in December 2008 that the treatment vials were. FDA withdrew approval of both applications effective June 18, 2009. After a 2012 citizen petition, FDA reviewed its records and postmarketing adverse-event data and determined in 2013 that neither product was withdrawn for reasons of safety or effectiveness, which allows generic (ANDA) versions to be approved if they meet all other requirements (Federal Register, 2013; Drugs@FDA, Geref). Drugs@FDA still lists both strengths of Geref as discontinued, so there is no FDA-approved sermorelin product on the US market.

What the research shows

Children with GH deficiency

This is the indication sermorelin was approved for, and where nearly all of its trial data come from. The trials were mostly open-label (no placebo, patients and doctors aware of treatment), which is common in pediatric GH research but limits how firmly results can be read.

Study Design and n Regimen Main result
Thorner et al., 1996 (Geref International Study Group) Open-label, multicenter; 110 untreated prepubertal children, 86 analyzed for efficacy 30 µg/kg SC once daily at bedtime, up to 1 year Height velocity rose from 4.1 to 8.0 cm/yr at 6 months and 7.2 cm/yr at 12 months; 74% were good responders at 6 months
Lanes and Carrillo, 1994 (Venezuelan group) Open-label; 16 prepubertal children 30 µg/kg SC once daily, 12–24 months 11 of 16 (68.7%) responded; in responders height velocity rose from 3.4 to 6.5 cm/yr at 24 months; 5 non-responders switched to GH
Neyzi et al., 1993 Randomized, three arms; 43 children with GH deficiency of hypothalamic origin 30 or 60 µg/kg/day SC in 3 doses, vs GH 0.1 IU/kg/day, 6 months Height velocity lowest with the lower sermorelin dose; the higher dose was comparable to GH; only GH improved height SDS for bone age

In the Venezuelan study, bone age advanced by an amount equal to the time on treatment, and in the Geref trial bone-age progression kept pace with the gain in height age, so the faster growth did not come from accelerated skeletal maturation. A drug review concluded that sermorelin works in some prepubertal children with idiopathic GH deficiency, that its effect on final adult height was not established, and that it had never been compared directly with once-daily somatropin (recombinant GH) at the recommended dose. In indirect comparisons, gains in height velocity were smaller than with daily somatropin (Prakash and Goa, 1999).

In children who were not GH deficient (idiopathic short stature or GH neurosecretory dysfunction, n = 24), 6 months of 30 µg/kg nightly increased growth rate, but 6 months after stopping, growth rates were no longer different from before treatment (Schwartz et al., J Pediatr Endocrinol Metab 2000).

Older adults

The adult evidence is small and short. The idea behind it is that GH and IGF-I fall with age, and a GHRH analog might raise them while keeping natural feedback intact.

  • Sermorelin in older men. Eleven healthy men aged 64–76 with low baseline IGF-I injected 2 mg of GHRH(1-29) subcutaneously each night for 6 weeks, with measurements before and after treatment (the abstract describes no placebo group). Nighttime GH release and GH peak size increased, but IGF-I did not change. Two of six strength measures and one endurance test improved, while weight, DEXA-measured muscle and fat, glucose tolerance and lipids did not change. The authors concluded that single nightly doses were less effective than multiple daily doses (Vittone et al., Metabolism 1997).
  • A related analog, not sermorelin. A frequently cited 5-month study gave 19 adults aged 55–71 a GHRH(1-29) analog in which methionine at position 27 is replaced by norleucine, at 10 µg/kg nightly for 16 weeks after a 4-week placebo phase. IGF-I rose, and lean body mass increased in men but not in women; a transient rise in blood lipids was the only adverse effect reported (Khorram et al., JCEM 1997). Because the molecule differs from sermorelin, these results describe a relative, not sermorelin itself.

Body composition and performance in healthy adults

No controlled trial has tested sermorelin for fat loss, muscle gain or athletic performance in healthy adults. A 2026 clinical review of GH-axis peptides noted that sermorelin is commonly promoted as a “physiologic” way to raise GH for body-composition goals, but concluded that clinically meaningful benefits in healthy people remain uncertain because the human evidence is limited and largely indirect. It graded sermorelin on the strength of its historical pediatric approval, with no current approval for any performance or body-composition use (Dominikowski et al., 2026).

On “sermorelin is a natural alternative to HGH.” It is true that sermorelin works through the pituitary rather than replacing GH, so GH output stays under feedback control. That does not mean the effects match those of GH therapy. In the only head-to-head pediatric data, the standard sermorelin dose produced less growth than GH, and in older men 6 weeks of nightly sermorelin raised GH without raising IGF-I or changing body composition (Neyzi et al., 1993; Vittone et al., 1997).

Side effects and risks

Reported in trials

In pediatric use, single intravenous doses and daily subcutaneous doses were generally well tolerated, and the most common adverse events were transient facial flushing and pain at the injection site (Prakash and Goa, 1999). The 2026 review also lists nausea, dizziness, headache, rare allergic reactions and a small, rapid rise in prolactin (Dominikowski et al., 2026). In the 110-child Geref trial, no adverse changes in routine blood chemistry or hormones, no change in fasting glucose and no excessive rise in IGF-I were seen over a year (Thorner et al., 1996).

Antibodies

Antibodies against GHRH developed in a substantial share of treated children: in 4 of 11 responders at 6 months and 6 of 11 at 12 months, and in 2 of 5 non-responders. They did not appear to interfere with growth in that study (Lanes and Carrillo, 1994).

Long-term and theoretical risks

  • No long-term safety data. The review notes that no long-term safety data are available (Dominikowski et al., 2026).
  • GH and IGF-I signaling. Raising GH and IGF-I is flagged as a theoretical cancer concern across GH-axis peptides, with no established clinical cancer signal (Dominikowski et al., 2026).
  • Needs a working pituitary. Sermorelin cannot raise GH when the pituitary itself cannot make it, which is also why it was used to test pituitary function (Prakash and Goa, 1999).

Product quality

Since Geref was discontinued, no FDA-approved sermorelin product has been marketed in the US, so sermorelin in circulation today is not the approved product. The 2026 review notes that real-world use is complicated by quality-control uncertainty and variable composition in unregulated peptide supply chains (Dominikowski et al., 2026).

  • United States. Sermorelin was an approved prescription drug; FDA’s 2013 determination means a generic could be approved, but none is listed (Federal Register, 2013). Unlike CJC-1295, it does not appear on FDA’s list of bulk drug substances for compounding that may present significant safety risks (FDA bulk drug substances, category 2).
  • Not a controlled substance. It is not named in the DEA’s Schedule III anabolic steroid list (21 CFR 1308.13).
  • Banned in sport. The WADA 2026 Prohibited List prohibits growth hormone releasing factors at all times under S2.2.4, naming GHRH and its analogues, “e.g. CJC-1293, CJC-1295, sermorelin and tesamorelin.”

Key takeaways

  • The unmodified parent peptide. Sermorelin is the natural first 29 amino acids of GHRH; CJC-1295 and Mod GRF 1-29 are modified versions of the same fragment, and tesamorelin is a modified full-length GHRH.
  • Once an approved drug. Geref was FDA-approved for pediatric GH deficiency (1997) and pituitary testing (1990), discontinued in 2008, and FDA found it was not withdrawn for safety or effectiveness reasons.
  • Very short-lived. The peptide lasts minutes in plasma, though the GH pulse it triggers lasts a few hours.
  • Evidence is pediatric. Open-label trials showed faster growth in many GH-deficient children, with less growth than daily GH in comparisons; adult data are limited to small, short studies.
  • No proof for physique goals. No controlled trial supports sermorelin for muscle gain, fat loss or performance in healthy adults, and WADA bans it at all times.

Sources

  1. Esposito P, Barbero L, Caccia P, et al. PEGylation of growth hormone-releasing hormone (GRF) analogues. Adv Drug Deliv Rev. 2003;55(10):1279–1291. PubMed.
  2. Prakash A, Goa KL. Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs. 1999;12(2):139–157. PubMed.
  3. Food and Drug Administration. 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. Fed Regist. 2013;78(42):14095–14096. Federal Register.
  4. Food and Drug Administration. Drugs@FDA: Geref (sermorelin acetate), NDA 020443, discontinued. Drugs@FDA.
  5. National Center for Biotechnology Information. Sermorelin, PubChem CID 16132413. PubChem.
  6. Frohman LA, Downs TR, Williams TC, et al. Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus. J Clin Invest. 1986;78(4):906–913. PubMed.
  7. Soule S, King JA, Millar RP. Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. J Clin Endocrinol Metab. 1994;79(4):1208–1211. PubMed.
  8. Wilton P, Chardet Y, Danielson K, et al. Pharmacokinetics of growth hormone-releasing hormone(1-29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration. Acta Paediatr Suppl. 1993;388:10–15. PubMed.
  9. Jetté L, Léger R, Thibaudeau K, et al. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005;146(7):3052–3058. PubMed.
  10. Teichman SL, Neale A, Lawrence B, et al. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799–805. PubMed.
  11. Dominikowski A, Rękoś Z, Olejarz M, et al. The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration. Front Endocrinol (Lausanne). 2026;17:1822475. PubMed; PMC.
  12. Food and Drug Administration. Drugs@FDA: Egrifta (tesamorelin), BLA 022505, approved November 10, 2010. Drugs@FDA.
  13. Thorner M, Rochiccioli P, Colle M, et al. 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. J Clin Endocrinol Metab. 1996;81(3):1189–1196. PubMed.
  14. Lanes R, Carrillo E. Long-term therapy with a single daily subcutaneous dose of growth hormone releasing hormone (1-29) in prepubertal growth hormone deficient children. Venezuelan Collaborative Study Group. J Pediatr Endocrinol. 1994;7(4):303–308. PubMed.
  15. Neyzi O, Yordam N, Ocal G, et al. Growth response to growth hormone-releasing hormone(1-29)-NH2 compared with growth hormone. Acta Paediatr Suppl. 1993;388:16–21. PubMed.
  16. Schwartz ID, Grunt JA, Berg S, et al. Growth during and after a trial of growth hormone releasing hormone 1-29 in children with idiopathic short stature or growth hormone neurosecretory dysfunction. J Pediatr Endocrinol Metab. 2000;13(6):645–650. PubMed.
  17. Vittone J, Blackman MR, Busby-Whitehead J, et al. Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism. 1997;46(1):89–96. PubMed.
  18. Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab. 1997;82(5):1472–1479. PubMed.
  19. Food and Drug Administration. Certain bulk drug substances for use in compounding may present significant safety risks (category 2 under the interim policies). FDA.
  20. Drug Enforcement Administration. Schedule III controlled substances, 21 CFR 1308.13. 21 CFR 1308.13.
  21. World Anti-Doping Agency. 2026 Prohibited List, section S2.2.4 (growth hormone releasing factors), in effect 1 January 2026. WADA 2026 Prohibited List.