Sermorelin acetate: what the molecule is, what the Geref approval covered, what the trials measured, and what a COA has to show

What sermorelin is: the first 29 residues of GHRH#

Growth hormone-releasing hormone (GHRH, also written GRF) is the hypothalamic peptide that signals the anterior pituitary to make and release growth hormone. The 1982 paper that first characterized the hormone, from a human pancreatic tumor that produced it, also tested shorter pieces of the chain and reported that the fragment of residues 1 to 29 with an amidated C-terminus, hpGRF(1-29)-NH2, had full intrinsic activity and potency in vitro ^[2]. That 29-residue amide is sermorelin: the shortest piece of GHRH shown to keep the parent hormone's full activity at the receptor, and the piece that became the drug ingredient.

Identifiers for the free peptide amide, from PubChem: molecular formula C149H246N44O42S, molecular weight 3,357.9 g/mol, CAS registry number 86168-78-7, PubChem CID 16129620 ^[7]. The one-letter sequence is YADAIFTNSYRKVLGQLSARKLLQDIMSR-NH2, which is Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg with an amide at the C-terminus ^[7]. PubChem's synonyms include GRF(1-29)NH2, GHRH(1-29)NH2 and Geref ^[7]. Sermorelin is the international nonproprietary name; sermorelin acetate is the salt used in the former drug product and named on most research listings. The values above refer to the free peptide, not the salt.

Two other GHRH-derived peptides, tesamorelin and CJC-1295, are usually discussed alongside sermorelin; the three are compared further down this page.

Geref: sermorelin's history as an FDA-approved drug#

Sermorelin acetate reached the U.S. market as Geref, held by EMD Serono, through two new drug applications. The first, NDA 19-863, was approved on December 28, 1990. Its indication was "evaluating the ability of the somatotroph of the pituitary gland to secrete growth hormone", that is, a diagnostic test of pituitary function rather than a treatment ^[1]. The second, NDA 20-443, was approved on September 26, 1997, for "treatment of idiopathic growth hormone deficiency (GHD) in children with growth failure" ^[1]. Those are the only indications a regulator ever approved for the molecule, reported as the regulator worded them.

In letters dated July 11, December 2 and December 12, 2008, EMD Serono told the FDA that it had discontinued both presentations and asked that the approvals be withdrawn. The FDA announced the withdrawals in the Federal Register of May 19, 2009, effective June 18, 2009 ^[1]. A citizen petition filed in October 2012 asked the agency whether the products had been withdrawn for safety or effectiveness reasons, and on March 4, 2013 the FDA published its answer: after reviewing its files and the literature, it found that Geref "was not withdrawn for reasons of safety or effectiveness" ^[1]. Geref therefore stays in the Orange Book's discontinued drug product list and can serve as the reference product for a generic application ^[1]. None has been approved, which is why there is no approved sermorelin product in the United States.

What the sermorelin clinical trials measured#

Because sermorelin went through drug development in the 1980s and 1990s, it has human clinical data, though far less than tesamorelin and most of it in children. The table lists the main published studies and what each measured. Our guide to reading published peptide research explains the study types. Amounts and routes are omitted, as for every compound in this library.

Children with growth hormone deficiency#

The largest treatment study is the 1996 Geref International Study Group trial in the Journal of Clinical Endocrinology and Metabolism (PMID 8772599). It enrolled 110 previously untreated prepubertal children with growth hormone deficiency in an open-label, multicenter design and followed them for a year. Among the 86 children in the efficacy analysis, mean height velocity rose from 4.1 cm per year at baseline to 8.0 at six months and 7.2 at twelve months, and 74% were classed as good responders at six months. The ratio of change in bone age to change in height age was 1.04 at twelve months, not different from 1, so skeletal maturation kept pace with growth rather than running ahead of it. Fasting glucose did not change and IGF-I did not rise excessively ^[3]. There was no control group; the comparison is with each child's own pre-treatment growth rate.

The 1999 BioDrugs review by Prakash and Goa summarized the development program. It reported that height-velocity gains were maintained for 12 months, with a few children followed for up to 36 months, that most growth-deficient children achieved catch-up growth, and that slower-growing, shorter children with delayed bone and height age responded best. Two limitations stand out. Sermorelin was never directly compared with somatropin (recombinant growth hormone) under matched conditions, and in the comparisons that exist its height-velocity gains were smaller than with once-daily somatropin. And the effect on final adult height was unknown ^[4]. Both remain true, because no further pediatric trials were run after Geref left the market.

The diagnostic test#

Geref's first approval was as a provocative test: a single administration followed by blood sampling to see whether the pituitary released growth hormone when given its natural signal. The 1999 review called it a rapid and fairly specific test, with fewer false-positive responses in children without growth hormone deficiency than other provocative tests, and noted its limit: a normal response does not rule out a hypothalamic cause, so other tests are needed to confirm one. Transient facial flushing was the most common event reported with the test ^[4].

Small studies in older men#

Two studies from the National Institute on Aging group asked whether GHRH(1-29) changed the lower growth hormone and IGF-I levels seen in healthy older men. In the 1992 study, 10 healthy older men (mean age 68) and 9 young men (mean age 26) were characterized first; the older men had lower IGF-I, testosterone and phosphate and shorter spontaneous GH peaks. The older men then received GHRH(1-29) at two levels for 14 days each, in random order, with a washout between. Only the higher level significantly raised 24-hour GH, peak area, peak amplitude and IGF-I, after which these measures no longer differed from the young men; fasting glucose, urinary C-peptide, blood pressure and chemistry panels were unaffected ^[5]. The 1997 study used a once-nightly schedule in 11 non-obese men aged 64 to 76 with low IGF-I for six weeks, with no control group. Nocturnal GH release rose, but IGF-I, IGFBP-3 and GH-binding protein did not change, and neither did weight, BMI, waist-to-hip ratio, DEXA body composition, glucose or insulin responses, or lipids. Three of six strength tests changed. The authors concluded that a single nightly administration appeared less effective than several per day at producing IGF-I-mediated effects ^[6]. These are small, short physiology studies, not outcome trials.

What the sermorelin research does not cover#

• Final adult height. The pediatric program measured height velocity over one to three years, not adult height ^[4].
• A head-to-head trial against somatropin under matched conditions. The review found none ^[4].
• Adults with diagnosed growth hormone deficiency. The adult studies enrolled healthy older men with age-related low IGF-I, not patients with pituitary disease ^[5][6].
• Anything longer than six weeks in adults, or any placebo-controlled adult study beyond 14 days ^[5][6].
• Any comparison with tesamorelin or CJC-1295 in the same study. Each GHRH-derived peptide has its own literature.

Sermorelin's regulatory status in the United States and in sport#

There is no FDA-approved sermorelin product: the Geref approvals were withdrawn in 2009 at the manufacturer's request, and no generic has been approved since the 2013 determination ^[1]. The FDA's page on bulk drug substances used in compounding under section 503A explains that a substance may be used in 503A compounding if it has an applicable USP or NF monograph, is a component of an FDA-approved drug, or appears on the 503A bulks list, and it defines three categories for nominated substances ^[9]. The agency's list of nominated substances, updated May 14, 2026, does not name sermorelin or sermorelin acetate in any category ^[10]. Whether a formerly approved ingredient qualifies under the "component of an FDA-approved drug" route is a regulatory question outside the scope of a research-use library.

The 2026 WADA Prohibited List, in effect from January 1, 2026, names sermorelin by name under section S2.2.4, growth hormone releasing factors, as an example of a GHRH analogue alongside CJC-1293, CJC-1295 and tesamorelin. Section S2 is prohibited at all times, in and out of competition ^[8].

Sermorelin vs tesamorelin vs CJC-1295: the structural difference#

All three are built on the human GHRH sequence and act at the GHRH receptor, but they differ in length, modification and regulatory history. Sermorelin is the unmodified 1-29 amide. Tesamorelin is the complete 44-residue hormone with a trans-3-hexenoyl group on the N-terminal tyrosine; its label gives a molecular weight of 5,135.9 Da for the free base, and it is the active ingredient of Egrifta, approved in 2010 for one indication in adults with HIV ^[11]. CJC-1295 is a modified 1-29 amide; the version with a drug affinity complex (DAC) adds a linker designed to bind serum albumin, and the version without it is often sold as modified GRF (1-29). The CJC-1295 explainer covers the substitutions and the evidence.

Reading a sermorelin acetate Certificate of Analysis#

Renuvia lots are tested by Freedom Diagnostics Testing for HPLC-UV purity, LC-MS identity and measured content, and the certificates are posted in the COA library. At the time of writing the library shows the sermorelin acetate lot as pending: the laboratory report has not yet been posted, and no purity figure is stated here for that reason. When a sermorelin acetate COA is in front of you, from any supplier, check these points:

1. The mass spectrometry result should match the unmodified 29-residue amide, about 3,358 Da for the free peptide ^[7]. A mass near 5,136 Da is tesamorelin ^[11]; a mass matching a substituted or conjugated 1-29 sequence is CJC-1295 or modified GRF (1-29). The report should state the observed mass, not only a pass/fail line.
2. Purity and content are different numbers. HPLC purity is the fraction of peptide-related material in the main peak; measured content is the milligrams of peptide in the vial. Both should appear, and because the material is an acetate salt the report should say whether content is expressed as free peptide or as salt. Our peptide purity guide explains why the two are confused.
3. Sermorelin has a methionine at position 27 and an asparagine at position 8, which can oxidize and deamidate respectively during synthesis or storage and appear as small peaks next to the main peak. A report that quantifies them is more useful than one that rounds them away; see storing lyophilized peptides.
4. The lot number should match the vial, and the laboratory should be named with an accession number you can check; see verifying that a COA is genuine.
5. A sermorelin certificate should not reference Geref, an NDA or a drug-product specification. Research-grade material is not made under the former approval.

The guides to reading a Certificate of Analysis and to HPLC and mass spectrometry explain each section of a report.