Sermorelin is a laboratory-made peptide (a short chain of amino acids) that is a fragment of the natural hormone GHRH — the signal with which the brain tells the pituitary to release growth hormone. It is the first 29 amino acids of that hormone — the shortest piece that keeps full activity. Unlike most “research peptides” it has a genuine history as a medicine: in the USA it was approved as Geref — as a test of pituitary function and a treatment for children with growth-hormone deficiency — and it disappeared from the market in 2008 for reasons unrelated to safety. The human evidence is real but old and sparse: a few studies in children from the 1990s and a handful of small studies in older adults.
What sermorelin is
Natural GHRH has 44 amino acids. As early as the 1980s it was established that its beginning — 29 amino acids — is enough for full activity; that fragment was named GRF 1-29, or sermorelin. The review by Prakash and Goa (1999) describes it as the shortest synthetic peptide with the full biological activity of GHRH, which after intravenous or subcutaneous administration specifically stimulates growth-hormone secretion from the anterior pituitary. Today it is not an approved medicine — it is a research compound.
How it works
GHRH acts on a “switch” (a receptor) on cells of the pituitary — a small gland at the base of the brain — and triggers a burst of growth hormone (GH), which in turn raises IGF-1. Sermorelin does exactly the same, because it is a piece of that hormone. In the study by Gelander et al. (1989) in 20 short children, a single injection of the 1-29 fragment produced a growth-hormone burst of the same size as the fuller form GHRH 1-40 — along the way a brief, small rise in prolactin, LH and FSH was noted. Because sermorelin acts “at the top” of the axis, the natural brakes stay in place: in children (Thorner et al., 1996) no excessive rise in IGF-1 was observed.
Structure and duration of action
Sermorelin is 29 amino acids with a sequence identical to natural GHRH. It has no protection against enzymes, so it vanishes from the blood very quickly: the review by Dominikowski and colleagues (2026) gives a blood half-life of around 4 minutes. The growth-hormone burst itself lasts longer — in the study by Khorram et al. (1997), after an evening injection of a close analogue the GH release began within 10 minutes and lasted about 2 hours. This is the crux of the difference from the longer-acting analogues: tesamorelin (protected against the enzyme, half-life about half an hour) and CJC-1295 with DAC (days).
The diagnostic test
Sermorelin's first use was diagnostic: given intravenously, it checks whether the pituitary can release growth hormone. According to the Prakash and Goa review, the test gives fewer false-positive results than other stimulation tests, but a normal response does not rule out a deficiency of hypothalamic origin; in adults, combination with arginine was found to be more specific.
Human data — children with growth-hormone deficiency
The largest study (Thorner et al., 1996, Geref group): 110 children with growth-hormone deficiency received daily subcutaneous injections for a year, with no control group. Growth velocity improved from 4.1 cm/year before treatment to 8.0 cm/year at 6 months and 7.2 cm/year at 12 months; 74% of the children were judged good responders. Fasting glucose did not change. The only randomised study (Neyzi et al., 1993) compared, in 43 children, two doses of GHRH(1-29) with growth hormone itself for 6 months: the lower dose gave the smallest acceleration, the higher one — comparable to growth hormone, but only growth hormone improved height relative to bone age. The Adis review sums it up: gains in growth velocity were smaller than with somatropin, and the effect on final adult height was never established.
Human data — older adults
Corpas et al. (1992) gave 10 healthy men aged around 68 GHRH(1-29) twice a day for 14 days: at the higher of two doses, 24-hour GH secretion and IGF-1 returned to the values seen in 9 young men; glucose and blood pressure did not change. Vittone et al. (1997) gave 11 men aged 64–76 single evening injections for 6 weeks: overnight GH secretion rose, but IGF-1, body composition, body weight, glucose and lipids did not change; 2 of 6 measures of muscle strength improved. The authors conclude that one injection is less effective than several across the day. The longest study (Khorram et al., 1997; 19 people aged 55–71, 16 weeks, placebo-controlled) concerned a close analogue, [Nle27]GHRH(1-29), not sermorelin itself: IGF-1 rose within 2 weeks but by week 16 was returning towards baseline; skin thickness increased in both sexes, lean mass and insulin sensitivity — only in men; body weight and fat did not change. None of these studies measured hard endpoints (fractures, physical function, disease).
Why Geref disappeared from the market
The regulatory history is well documented in the US Federal Register. The diagnostic form of Geref was approved in December 1990, and the form for treating children with idiopathic growth-hormone deficiency in September 1997. In 2008 the company EMD Serono notified the discontinuation of both forms, and the FDA withdrew the approvals effective 18 June 2009. In 2013, in response to a citizen petition, the FDA formally determined that Geref was not withdrawn from sale for reasons of safety or effectiveness. The review by Dominikowski and colleagues (2026) interprets this as a commercial decision; by then recombinant growth hormone was the standard treatment.
Safety and the limits of the evidence
Sermorelin was well tolerated in the studies: the most commonly reported effects were transient facial flushing and pain at the injection site (Prakash and Goa, 1999). With the [Nle27] analogue only transient hyperlipidaemia was noted. The limitations, however, are serious: the studies are old (1989–1997), small (10–110 people) and mostly without placebo; in older adults the effects on IGF-1 depended on how often the peptide was given and faded over time, and body composition changed little or not at all; there are no data at all on multi-year safety or on the effect of prolonged stimulation of the GH–IGF-1 axis on cancer risk — the 2026 review calls this a theoretical but unstudied risk. We deliberately give no methods of use and no doses.
The wider context — GHRH analogues
Sermorelin is the “template” of the GHRH-analogue family: the modifications that protect against enzymes start from it. Tesamorelin is the only one that reached phase 3 trials and approval. CJC-1295 has four amino-acid substitutions (the DAC version also a hook that binds albumin); the version without DAC, Mod GRF 1-29, has no human studies — its presumed action is inferred from the sermorelin studies. A separate group are the ghrelin mimetics such as ipamorelin, which stimulate growth hormone through a different receptor.
Summary
Sermorelin is the 1-29 fragment of the hormone GHRH — short-acting, selective for growth hormone, with a genuine though closed history as a medicine (Geref, 1990–2009, withdrawn for commercial reasons). In children with GH deficiency it accelerated growth, but less than growth hormone; in older adults it raised GH, and IGF-1 only with frequent administration and transiently, without clear changes in body composition. State of the evidence: moderate in the former paediatric indication, weak and old in every other — and long-term safety remains unstudied.
Sources
- 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):139–57. PMID: 18031173. DOI: 10.2165/00063030-199912020-00007. pubmed.ncbi.nlm.nih.gov/18031173
- 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. Journal of Clinical Endocrinology and Metabolism. 1996;81(3):1189–96. PMID: 8772599. DOI: 10.1210/jcem.81.3.8772599. pubmed.ncbi.nlm.nih.gov/8772599
- Neyzi O, Yordam N, Ocal G, et al. Growth response to growth hormone-releasing hormone(1-29)-NH2 compared with growth hormone. Acta Paediatrica Supplement. 1993;388:16–21. PMID: 8329826. DOI: 10.1111/j.1651-2227.1993.tb12828.x. pubmed.ncbi.nlm.nih.gov/8329826
- Corpas E, Harman SM, Piñeyro MA, et al. 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 and Metabolism. 1992;75(2):530–5. PMID: 1379256. DOI: 10.1210/jcem.75.2.1379256. pubmed.ncbi.nlm.nih.gov/1379256
- 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: Clinical and Experimental. 1997;46(1):89–96. PMID: 9005976. DOI: 10.1016/s0026-0495(97)90174-8. pubmed.ncbi.nlm.nih.gov/9005976
- 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. Journal of Clinical Endocrinology and Metabolism. 1997;82(5):1472–9. PMID: 9141536. DOI: 10.1210/jcem.82.5.3943. pubmed.ncbi.nlm.nih.gov/9141536
- Gelander L, Lindstedt G, Selstam G, et al. Effects of acute intravenous injection of two growth hormone-releasing hormones (GHRH 1-40 and 1-29) on serum growth hormone and other pituitary hormones in short children with pulsatile growth hormone secretion. Hormone Research. 1989;31(5–6):213–20. PMID: 2515143. DOI: 10.1159/000181119. pubmed.ncbi.nlm.nih.gov/2515143
- 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. Frontiers in Endocrinology. 2026;17:1822475. PMID: 42395176. DOI: 10.3389/fendo.2026.1822475. pubmed.ncbi.nlm.nih.gov/42395176
For in-vitro laboratory research only. It is not a human medicine and is not for treatment.