Sermorelin

Growth hormone-releasing hormone was first isolated in 1982, not from the brain but from pancreatic tumours that had caused acromegaly by secreting it. Roger Guillemin’s group and Wylie Vale’s group both published their characterisations that year ^[1][2]. The natural hormone is 44 amino acids long, but a shorter fragment made of its first 29 amino acids still releases growth hormone. Sermorelin is that 1-29 fragment, made synthetically with an amide at the end ^[6].

It is the simplest of the GHRH analogues on this site. Tesamorelin keeps all 44 amino acids and adds a stabilising chemical group; CJC-1295 starts from the same 1-29 sequence as sermorelin but swaps four amino acids and, in its DAC form, adds a group that binds to albumin to extend its life in the blood. Sermorelin has none of these modifications, so it acts briefly.

Sermorelin binds the GHRH receptor on the pituitary and triggers a burst of growth hormone (GH) release, which then raises insulin-like growth factor 1 (IGF-1). Because it works through the pituitary rather than replacing GH directly, the release remains subject to the body’s own brakes, principally somatostatin and IGF-1 feedback.

Native GHRH fragments are broken down quickly in the blood, partly by the enzyme DPP-4. That short duration was the practical problem that later analogues were designed to solve; CJC-1295, for example, was engineered for stability against DPP-4 and a longer half-life ^[3]. For sermorelin it means the GH pulse after each injection is short, which is why studies gave it daily or more often.

Sermorelin’s pathway is distinct from the ghrelin-receptor pathway used by ipamorelin and the GHRPs, and early human studies showed that GHRH and a GH-releasing peptide given together produce a greater-than-additive GH response ^[4].

The main clinical programme was in prepubertal children with growth hormone deficiency, which is what the Geref licence was based on. In a multicentre open-label study by the Geref International Study Group, 110 previously untreated children received 30 µg/kg sermorelin under the skin at bedtime for up to a year. Mean height velocity rose from 4.1 cm/year at baseline to 8.0 cm/year at six months and 7.2 cm/year at 12 months, and 74% were judged good responders at six months; no adverse biochemical changes were reported ^[5].

A 1999 drug review concluded that sermorelin was a useful diagnostic test for GH deficiency when given as a single intravenous 1 µg/kg dose alongside conventional tests, and that limited data supported daily treatment in some children. It noted that growth responses were lower than with daily somatropin (recombinant GH) in the studies available, and that its effect on final adult height had not been established ^[6].

That comparison with growth hormone itself is worth spelling out, because sermorelin is often promoted as a “natural” alternative to GH injections. The review found that the recommended sermorelin dose had not been compared directly with somatropin; in the studies that did exist, height gains with sermorelin given by continuous infusion or three divided doses were smaller than with daily somatropin at a similar per-kilogram dose ^[6]. Sermorelin also depends on a pituitary that can still make GH, so it is not a substitute in people whose pituitary cannot respond.

Sermorelin’s first licensed use was diagnostic. A single intravenous dose of 1 µg/kg tests whether the pituitary can release GH. According to the 1999 review, it was rapid and relatively specific, with fewer false-positive results in children without GH deficiency than other stimulation tests, and in adults the combination of sermorelin with arginine was more specific still ^[6]. The review also noted a limitation: because sermorelin acts directly on the pituitary, a normal response cannot rule out GH deficiency caused by a problem in the hypothalamus, so other tests are still needed ^[6].

Much of today’s interest in sermorelin concerns adults with age-related decline in GH, but the evidence here is thin. In a small study in Baltimore, 10 healthy older men took GHRH(1-29), the same sequence as sermorelin, as 0.5 mg or 1 mg injections twice daily for 14 days. The higher dose raised 24-hour GH and IGF-1 to levels no longer different from those of young men, without changing glucose or blood pressure ^[7].

A follow-up study gave 11 healthy men aged 64 to 76 a single 2 mg injection each night for six weeks. Night-time GH release increased, but IGF-1, body composition, weight and lipids did not change; two of six strength measures and one endurance test improved. The authors concluded that single nightly doses were less effective than multiple daily doses ^[8]. Taken together with the earlier twice-daily study, in which IGF-1 did rise ^[7], this is consistent with sermorelin’s short action: one daily pulse may not be enough to raise IGF-1 in older adults. There are no large or long-term randomised trials of sermorelin for ageing, body composition or athletic performance.

Sermorelin has more human data than most research peptides because it was a licensed drug: paediatric efficacy studies ^[5], a diagnostic-test literature ^[6], and a handful of short physiological studies in older men ^[7][8]. What it lacks is modern, adequately sized, placebo-controlled trials in adults. Claims about anti-ageing, fat loss or muscle gain in adults rest mostly on extrapolation from its effect on GH and IGF-1 rather than on outcome trials.

The two are often compared because both stimulate GH through the GHRH receptor. The differences are in structure and in the evidence. Sermorelin is the unmodified 1-29 fragment, short-acting, and its trial evidence is mainly paediatric plus small adult studies ^[5][7][8]. Tesamorelin is the full 44-amino-acid hormone with a stabilising hexenoyl group, and it has phase 3 randomised trials showing reduced visceral fat in people with HIV and a current US and Canadian licence for that use. They have never been compared head to head, so there is no direct evidence that either is more effective for any outcome.

Studies used quite different regimens depending on the purpose. As a diagnostic test, a single intravenous dose of 1 µg/kg was used ^[6]. For treating children with GH deficiency, the licensed regimen studied was 30 µg/kg under the skin once daily at bedtime ^[5][6]. In older men, studies used 0.5 mg or 1 mg twice daily for 14 days ^[7] and 2 mg once nightly for six weeks ^[8].

These are the doses reported in the cited studies, not recommendations. For converting between milligrams, micrograms and injection volumes in a laboratory setting, see our peptide calculator.

In the clinical literature sermorelin was generally well tolerated. The most commonly reported adverse events were transient facial flushing and pain at the injection site ^[6]. Flushing is a recognised effect of GHRH itself: in an early study of the full-length hormone, 16 of 18 men had brief flushing after an intravenous dose ^[4]. The paediatric trial reported no adverse changes in routine blood tests, fasting glucose or IGF-1 ^[5].

Because it raises GH and IGF-1, the theoretical concerns that apply to other GH-axis drugs (fluid retention, effects on glucose, and a hypothetical effect on existing tumours) apply here too, but the adult studies were too small and short to measure them. Safety data from a licensed pharmaceutical product also do not transfer to unlicensed research-grade material of unknown purity.

In the US, sermorelin acetate was approved as Geref in two forms: a 0.05 mg ampoule in December 1990 for testing the pituitary’s ability to secrete GH, and 0.5 mg and 1.0 mg vials in September 1997 for treating idiopathic GH deficiency in children with growth failure. The holder, EMD Serono, discontinued both in 2008 and the FDA withdrew approval with effect from 18 June 2009. In March 2013 the FDA published a determination that Geref was not withdrawn from sale for reasons of safety or effectiveness, which in principle allows generic applications ^[9].

It is sometimes said that sermorelin was “withdrawn because it didn’t work” or “banned by the FDA”; neither is accurate according to that determination. Equally, there is currently no FDA-approved sermorelin product on the market. We could not confirm a current licence in the UK, Canada, Australia or New Zealand. See our legal status overview, including the US page.

Sermorelin is named on the WADA Prohibited List under S2 (GHRH and its analogues) and is banned at all times ^[10].

Research-grade sermorelin is sold as a freeze-dried powder. There are no published stability studies for these products, so storage follows general practice for lyophilised peptides; see our guides to storing peptides and bacteriostatic water.

Sermorelin is widely stocked and relatively cheap per milligram. Compare prices, check any certificate of analysis with our guide on how to read a COA, and prefer third-party tested suppliers.