The short version

Five things, before anything else.

• It was a real drug, twice. Geref Diagnostic (NDA 19-863, 28 December 1990) and Geref (NDA 20-443, 26 September 1997). Both approvals were withdrawn effective 18 June 2009, at the sponsor's own request, because it had stopped selling them.
• It lost head-to-head to growth hormone. The drug's own comprehensive review states that at the same 30 µg/kg/day, height-velocity gains on sermorelin “were less than” those on somatropin. In the one study that gave the same seven children both, five of seven failed on sermorelin and all seven responded to rhGH.
• The half-life is eleven minutes. That is not a footnote. It is the reason tesamorelin, CJC-1295 and Mod GRF (1-29) exist — every one of them is an attempt to fix this exact molecule's front end.
• The famous cognition trial was not sermorelin. Baker 2012, the study quoted everywhere for “GHRH improves cognition,” used tesamorelin. So did the 2013 follow-up. So did the 2026 one, which was null.
• Of fourteen peptides in the largest public quality survey, sermorelin had the lowest measured content. Median 97.45% of label, with the lower quartile falling under 89%. Its characteristic failure is being underfilled — which is exactly why the assay number on the certificate matters more here than almost anywhere else.

What sermorelin is

The first twenty-nine residues of a forty-four residue hormone, with the end capped. Nothing else changed. That is the whole molecule, and it is also the whole problem.

Human growth hormone-releasing hormone is secreted by the hypothalamus as a 44-residue peptide, amidated at the C-terminus. Truncation work in the early 1980s established that the biological activity lives in the N-terminal region, and that the amidated 1-29 fragment is essentially equipotent with the full-length hormone at the receptor. Sermorelin is that fragment — the shortest fully active piece of GHRH.

It is not Mod GRF (1-29), and it is not CJC-1295

This confusion is constant in the market and it is worth being precise about. Mod GRF (1-29) carries four substitutions — D-Ala², Gln⁸, Ala¹⁵, Leu²⁷. CJC-1295 with DAC adds a linker that binds albumin covalently. Sermorelin has none of that. It is the unmodified native sequence.

The two are about ten daltons apart, which is trivially resolvable by mass spectrometry — if mass spectrometry is actually run at adequate resolution. In the same survey that measured content, CJC-1295 had the second-highest identity failure rate of fourteen peptides, at 9.1%. Misidentification inside this structural family is demonstrably common.

The C-terminal amide is not decoration

The chain ends in –CONH₂, not a free acid, mirroring the native hormone. Losing that amide costs potency and gains 0.98 Da. Remember that number — it comes back three separate times in the impurity section, and a certificate that reports mass to the nearest dalton cannot tell any of them apart.

Six basic sites — the N-terminal amine, three arginines and two lysines — against two aspartates. Net charge near +3 at pH 7. The molecule is strongly cationic, freely water-soluble, and carries a high counterion demand, which is why acetate content on a certificate is usually several molar equivalents rather than one.

Eleven minutes

Every other GHRH analogue in existence is a response to this one number.

From the Geref label: elimination half-life 11–12 minutes after either intravenous or subcutaneous administration. Subcutaneous bioavailability approximately 6%. Clearance 2.4–2.8 L/min. Time to peak sermorelin concentration after a subcutaneous dose, 5–20 minutes.

What is eating it

The chain begins Tyr¹-Ala²-Asp³. An N-terminal X-Ala motif is the textbook substrate for dipeptidyl peptidase-4, a serine exopeptidase abundant in plasma and on endothelium. DPP-4 clips the Ala²–Asp³ bond, removes the first two residues, and leaves GHRH(3-29).

Frohman and colleagues measured what that costs. The clipped product is fully immunoreactive — an antibody assay cannot see the difference — but its biological activity is less than one thousandth that of the parent. In the same work, plasma half-life measured by total immunoreactivity was 63 minutes; measured by HPLC for intact peptide, 17. The gap between those two numbers is the dead metabolite.

A second liability sits in the middle of the chain. The 1989 follow-up found that GHRH(1-29)-NH₂ specifically is also cleaved rapidly at a trypsin-like site around Arg¹¹–Lys¹²–Val¹³. Sermorelin has two proteolytic soft spots, not one.

Why it cannot simply be fixed

Here is the design trap: Tyr¹-Ala²-Asp³ is simultaneously the receptor activation domain and the protease recognition motif. You cannot armour the front end without touching the business end.

Note what tesamorelin does. DPP-4 is an aminodipeptidase — it needs a free, protonated N-terminal amine to dock the substrate. Acylate that amine and the recognition handle is gone. It is the cleanest possible confirmation that the mechanism above is correct: block the N-terminus, and the short half-life problem disappears.

Note also the Gln⁸ and Leu²⁷ substitutions in Mod GRF. Those are not pharmacokinetic changes at all — they remove the deamidation site and the oxidisable methionine. Sermorelin, being unmodified, carries both. They come up again in storage.

The approval, and why it did not hold

Sermorelin was approved to grow children. It did grow them — just not as well as the drug it was supposed to improve on.

The pivotal trial

Geref's 1997 approval for idiopathic growth hormone deficiency in children rested on the Geref International Study Group trial, published in JCEM in 1996.

That is a real drug effect on a real measure. It is also an uncontrolled, open-label, before-and-after comparison in a condition where height-velocity measurement is subject to observation effects and regression to the mean. And the number went down between six and twelve months.

One more absence worth naming: no sermorelin trial ever reported final adult height. Every published outcome is an interim height-velocity figure. A drug that accelerates growth in year one without changing where a child finishes has delivered nothing.

Butenandt 1989 — the result that should decide this page

Seven children with growth hormone deficiency of hypothalamic origin — precisely the population in whom a GHRH analogue should work, because the pituitary is intact and only the signal upstream is missing. All seven were confirmed responders: every one produced an acute GH rise to an intravenous GHRH(1-29) bolus, mean 10.7 ng/mL.

Even in one of the two responders the effect did not hold: 8.2 cm/yr falling back to 5.4. The authors' conclusion, in their words: “Presently GHRH cannot be recommended for the routine therapy of children with growth hormone deficiency since a single daily dose of rhGH produced catch-up growth which GHRH therapy did not.”

The dose-matched comparison

From BioDrugs 1999, the drug's own comprehensive review: height velocity increases on subcutaneous sermorelin 30 µg/kg/day “were less than those in children receiving once daily subcutaneous somatropin 30 µg/kg bodyweight.” Same dose, same route, same schedule. The companion trade summary of that review ran under the title “Sermorelin: No Sizable Gains Over Somatropin.”

The earlier Lancet series is consistent: 18 prepubertal GH-deficient children, height velocity rose in 12 — meaning six of eighteen did not respond — and four children previously doing well on human GH experienced unexpected growth deceleration after switching.

The diagnostic test that missed half the cases

Geref Diagnostic came first, in 1990, and it failed for a reason that is worth understanding — because the same reason limits the drug.

The GHRH stimulation test injects sermorelin and measures the GH response. It therefore tests the pituitary. It bypasses the hypothalamus entirely.

That is a fatal design flaw for the commonest form of the disease. Most “idiopathic” growth hormone deficiency is hypothalamic in origin: the pituitary is fine, it simply never gets the signal. Give such a patient exogenous GHRH and the pituitary answers normally — and the test calls a genuinely deficient patient healthy.

The number

Arrigo and colleagues, European Journal of Pediatrics 1992: 48 children with GH deficiency against 20 controls. On average the test separated the groups cleanly — mean GH peak 15.2 versus 37.5 ng/mL, p < 0.001. Individually it did not.

A test that returns a normal result in 56% of genuinely deficient children is not a usable standalone diagnostic. Note the asymmetry with what the drug's review claimed: sermorelin produced fewer false positives than other provocative agents. That is about specificity. Arrigo is about sensitivity. Both can be true at once — the test rarely calls a normal child deficient, and frequently calls a deficient child normal.

The combined test was genuinely good, and it died commercially

Arginine suppresses hypothalamic somatostatin tone. Combine it with GHRH and you get a much larger, more reproducible response. GHRH+arginine was for roughly fifteen years the leading alternative to the insulin tolerance test in adults, with BMI-stratified cut-offs (<11 µg/L below BMI 25, <8 between 25 and 30, <4 above 30) and a reputation for convenience, reproducibility and discriminatory power.

It disappeared in the United States because the manufacturer stopped making the drug in November 2008. Not because something better arrived. The field fell back to the glucagon stimulation test, and later forward to oral macimorelin.

The distinction matters for how this page is read. The standalone GHRH test was abandoned on merit. The combined test was abandoned on supply. Anyone telling you GHRH testing was superseded by better science is describing only half of it.

The adult evidence

Sermorelin was never approved for any adult indication, anywhere. The adult literature is four or five small physiology studies, and they do not agree with each other.

Vittone 1997 — the study that should be quoted more than it is

Eleven healthy men aged 64–76, selected for low baseline IGF-1, given 2 mg subcutaneously every night for six weeks. That is a high dose — several times what circulates in commercial practice today.

Merriam and Vitiello — the strongest positive data, and what it also found

The Seattle group ran two six-month studies of once-nightly GHRH(1-29) in healthy older men and women. Their 2001 report confirms the compound was GHRH(1-29)NH₂ — sermorelin itself, not an analogue. Results:

• Lean body mass increased.
• Body fat reduced by 5–8%, greatest effect on abdominal visceral fat.
• IGF-1 up around 35%.
• Effects blunted in estrogenised women.
• No improvement in strength or aerobic fitness.
• Sleep quality was not improved — late-night GH secretion actually decreased after the initial stimulated surge.
• Physical function: the authors' own word is “equivocal.”

Duration is the most plausible reconciliation with Vittone — six months against six weeks. Vittone's own conclusion pointed the same way: single nightly doses are less effective than multiple daily ones.

Khorram 1997 — and the caveat nobody carries

The two Khorram papers are cited constantly as sermorelin evidence. They used [Nle²⁷]GHRH(1-29)-NH₂ — a norleucine-27 substituted analogue that replaces the oxidation-prone methionine. Related, not identical. With that stated, in 19 subjects aged 55–71 over 16 weeks: IGF-1 rose, skin thickness increased, lean body mass increased in men only (+1.26 kg), and there was no change in fat mass, no change in bone mineral density and no change in body weight.

Corpas 1992 — two weeks, hormones only

Nine young and ten old men, GHRH(1-29) twice daily for 14 days at each of two dose levels. In older men the high dose raised 24-hour mean GH, pulse amplitude and IGF-1, to the point where they were no longer statistically distinguishable from young men. This is the origin of the “restores youthful GH levels” line. No body composition was measured. It is a fourteen-day pharmacology study with no clinical endpoint.

Sigalos 2017 — read what it actually was

Frequently cited as clinical evidence for sermorelin. It is a retrospective chart review: 105 hypogonadal men screened, 14 analysed, given a three-drug combination of GHRP-6, GHRP-2 and sermorelin. IGF-1 rose from 159.5 to 239.0 ng/mL. No clinical outcome and no body composition were measured at all — the authors state anthropomorphic data were lacking.

The cognition trial that was not sermorelin

This one is worth its own section, because the error is everywhere and it is easy to see how it happened.

Baker LD et al., Archives of Neurology 2012 — 152 adults enrolled, 137 completed, 20 weeks, double-blind, placebo-controlled. Overall cognition improved (p = 0.03 intention-to-treat, 0.002 in completers), executive function p = 0.005, verbal memory a non-significant trend at 0.08. A genuinely good trial.

The study drug was tesamorelin, described in the paper as a stabilised analogue of human GHRH, 1 mg daily. Sermorelin was not used.

The confusion is understandable. The paper's title says “growth hormone-releasing hormone.” The press coverage said GHRH. And the senior authors were the same Seattle team who had previously run sermorelin studies — they simply changed molecules. Everything downstream used tesamorelin too: the 2013 JAMA Neurology GABA study, and the 2026 pilot in eNeurologicalSci, which was null on its primary measures in 22 participants.

Was there ever a sermorelin cognition trial? Probably one

Vitiello et al., Neurobiology of Aging 2006 — 89 healthy older adults, six months, double-blind and placebo-controlled, reporting improvements in working memory, problem-solving and psychomotor processing, strongest in those with lower baseline scores. NCBI's Endotext describes this as a trial of sermorelin acetate, and the group's own 2001 paper confirms their normal-ageing programme used GHRH(1-29)NH₂.

We list it because it appears to be real. But be clear about what it is: a single result, never independently replicated, from a group that then moved to a different molecule — and the better-known trials that followed, with the better-behaved drug, have not settled the question either.

Sleep, heart, immune — what is and is not there

Three claims that travel with this compound. One is half-true, one is empty, one is biomarkers only.

Sleep

The acute effect is real and nicely demonstrated. Marshall et al., JCEM 1996: the same 200 µg total given as four boluses significantly increased stage-4 slow-wave sleep against both placebo and a continuous infusion of the identical dose (both p < 0.01). The continuous infusion did essentially nothing — which is itself the cleanest published demonstration that the somatotroph desensitises to continuous GHRH exposure, and the reason every clinical protocol ever written used intermittent boluses.

But that was young subjects, acutely. In the elderly the effect is blunted, chronic dosing did not restore it, and in the only six-month controlled sermorelin programme in older adults sleep quality did not improve and late-night GH secretion fell after the initial surge.

“Sermorelin improves sleep” is not supported in the population it is sold to. It is supported acutely, in young people, under polysomnography.

Heart

There are no controlled sermorelin cardiac outcome data. None. Every “GH and the heart” trial that surfaces on searching — including the 2025 randomised trial in heart failure with reduced ejection fraction and the 2024 meta-analysis — used somatropin. Those are a different drug and must not be read across. The only cardiovascular observation anywhere in the sermorelin literature is the incidental drop in systolic pressure in Vittone's eleven men.

Immune

The second Khorram paper reported increases in lymphocyte surface markers and mitogen responsiveness in the same 19 subjects — CD20+ B cells up 30%, mitogen responses up 50%, IL-2 receptor expression up 70%. Again, that was the norleucine analogue. And more importantly: these are surface-marker counts, not clinical immunity. No infection rates, no vaccine responses, no clinical endpoints, n = 19, single-blind, one centre, never replicated.

Glucose and bone

The paediatric registration trial found no change in fasting glucose over twelve months. Khorram reported improved insulin sensitivity in men and no change in bone mineral density over sixteen weeks. At the category level, the 2018 Sexual Medicine Reviews paper notes general concern about decreased insulin sensitivity across growth hormone secretagogues.

Regulatory status, stated precisely

This is the section most often got wrong, in both directions. Sermorelin is neither an approved drug nor a banned one.

The sentence everyone misquotes

On 4 March 2013, in 78 FR 14095, the FDA determined under 21 CFR 314.161 that the Geref products “were not withdrawn for reasons of safety or effectiveness,” and that abbreviated new drug applications referencing them may be approved “as long as they meet all other legal and regulatory requirements.”

That determination is real, and it is in sermorelin's favour. It is also procedural. Here is exactly what it does and does not mean.

• It does remove one specific barrier to a generic application. Section 314.161 requires the FDA to make this finding before approving an ANDA that references a withdrawn drug.
• It does record that the withdrawal was commercial — the sponsor asked, because it was no longer selling the product.
• It is not an approval, a re-approval, a relisting or a licence.
• It is not a finding that sermorelin is safe. The FDA made no affirmative safety assessment. It found the absence of a safety-driven withdrawal, which is a different thing.
• No generic has been approved since. Thirteen years on, the determination has produced nothing.

The one FDA-commissioned review

In December 2020 the University of Maryland's regulatory science centre produced a summary report on sermorelin acetate for the FDA. Its evidence finding is worth knowing: only two clinical studies met the review's inclusion criteria, both from 1996, both conducted in Italy. The report makes no recommendation either way. It is the most neutral document that exists on this compound.

Sport

Sermorelin is named by name in WADA's Prohibited List, section S2.2.4, growth hormone releasing factors, alongside CJC-1293, CJC-1295 and tesamorelin. It is prohibited at all times — in and out of competition — and the wording has been stable across the 2025 and 2026 lists. Detection methods for synthetic GHRH analogues are published and validated.

The underfill problem — and why we publish the assay

Of all fourteen peptides in the largest public quality survey, sermorelin came last on measured content. Not on purity. On how much is actually in the vial.

Mendias and Awan, 2026, working from a third-party testing dataset: 6,285 samples across 203 manufacturers, seventeen months, fourteen compounds, analysed by HPLC with UV or MS detection.

Read the interquartile range rather than the median. A quarter of sermorelin samples contained less than about 89% of the labelled amount — below the floor of even the lenient compounding standard. The paper's own summary of the whole dataset is that “dosing inaccuracy represented the dominant quality deficit.”

Why sermorelin specifically

Most of it is salt-form arithmetic, and it is honest-looking rather than fraudulent.

Sermorelin is supplied as an acetate salt of a peptide with six basic sites. Real material carries roughly 1.5 to 3.5 acetate equivalents plus residual water. A vial filled to 5 mg of gross weighed powder at three acetates and 5% water contains about 4.3 mg of peptide. Nobody has lied; the label simply measured the wrong thing.

The second route is salt substitution. Peptides come off preparative HPLC as TFA salts, because trifluoroacetic acid is the ion-pairing agent. Converting to acetate takes a deliberate extra step that cheap suppliers skip. A TFA salt is heavier per mole, so the same gross weight contains less peptide — and residual TFA is cytotoxic in cell culture at concentrations these salts easily reach, which confounds any in-vitro use.

What a sermorelin certificate should show

• The sequence written out, with the –NH₂ shown explicitly.
• RP-HPLC at 214 nm with the chromatogram, retention time and the impurity table. Purity quoted at 280 nm only is a red flag — 280 sees only the two tyrosines and will miss truncated fragments entirely.
• A mass spectrum, not just the sentence “MS conforms.” On ESI a peptide with six basic sites gives no useful singly-charged ion; the base peak is the 3+ near m/z 1119.6 or the 4+ near 840.0.
• Net peptide content, water by Karl Fischer, acetate, residual TFA.
• Named impurities — deamidated at Asn⁸, Met²⁷ sulfoxide, the des-amido free acid, deletion sequences, aspartimide.

Here is the analytical trap worth carrying away. Three separate degradation routes each add 0.98 Da — Asn⁸ deamidation, glutamine deamidation, and hydrolysis of the C-terminal amide. A certificate reporting “3358, conforms” on a linear MALDI instrument cannot distinguish any of them from the parent, or from each other. Only chromatographic separation plus high-resolution or tandem MS can.

Reconstitution and handling

Sermorelin is one of the easy ones to get into solution. It is one of the harder ones to keep there.

Solubility

Strongly cationic, freely water-soluble, not aggregation-prone. There is no practical solubility ceiling at research concentrations — 1 to 10 mg/mL is comfortable.

Technique

1. Let the vial reach room temperature before piercing the stopper. A cold vial opened into humid air condenses moisture onto a hygroscopic cake, and residual water is the single biggest driver of solid-state degradation.
2. Direct the diluent against the glass wall, not onto the cake. The original label says exactly this.
3. Swirl gently. Do not shake or vortex. Sermorelin is surface-active; agitation foams it, denatures it at the air–water interface and loses it to adsorption.
4. Dissolution should take seconds. The solution should be clear and colourless. Haze, particulates or colour means reject the vial.

Arithmetic for a 5 mg vial

2.5 mL into a 5 mg vial is the pairing we would use in the lab, because every common increment then lands on a whole number of syringe graduations rather than a fraction.

What was actually in the pharmaceutical vial

Worth knowing, because it tells you what a well-made sermorelin product looks like. Geref was supplied as a sterile lyophilised powder containing the sermorelin acetate, 5 mg of mannitol as bulking agent, and dibasic and monobasic sodium phosphate as buffer. Not glycine — mannitol. Reconstituted pH 5.0–5.5. The diluent packaged with it was 2 mL of 0.9% sodium chloride, preservative-free.

The ten-to-one mannitol ratio is not padding. Half a milligram of peptide alone will not form a mechanically sound lyophilisation cake.

Storage — dryness beats cold

The most useful stability fact about this molecule is counter-intuitive, and it is backed by real data rather than convention.

The three things that degrade it

Asn⁸ deamidation. The sequence runs Thr⁷-Asn⁸-Ser⁹, and an Asn-Ser pair is a fast-deamidating motif: the small flexible neighbour lets the backbone attack the side-chain carbonyl, forming a cyclic succinimide that hydrolyses to a roughly 3:1 mixture of iso-aspartate and aspartate. Cost: +0.98 Da and a compromised molecule. This is the dominant solution-phase route, and it is the reason Mod GRF carries a Gln⁸ substitution.

Met²⁷ oxidation. To the sulfoxide, +16 Da, driven by dissolved oxygen, light, peroxides and trace metal ions. The most likely “aged vial” degradant after deamidation, and the reason Mod GRF carries Leu²⁷.

Aspartimide at Asp³ and Asp²⁵. The same succinimide chemistry without needing deamidation first, and it is acid-catalysed. So very low pH is not a safe harbour either.

The stability optimum for this family is around pH 5.5–6.0. Deamidation accelerates above 6.5; aspartimide formation accelerates below 4.5. The Geref reconstituted pH of 5.0–5.5 sits deliberately in that window.

Light

The European marketing authorisation carried an explicit “protect from light” instruction. Mechanistically it should: two tyrosines and a phenylalanine absorb in the UV, the excited aromatics generate reactive oxygen species, and those oxidise Met²⁷. Tryptophan — the worst offender — is absent, which helps, but the tyrosine-plus-methionine combination is enough to warrant it.

Freeze–thaw

No sermorelin-specific study exists. The mechanistically sound position: the dry powder is not meaningfully freeze–thaw sensitive — there is no bulk water to form ice, and the real risk on removal from a freezer is condensation onto the cake. The reconstituted solution is. Ice-front formation concentrates peptide and buffer locally, and phosphate buffers are notorious for pH swings of more than a unit during freezing as the two salts crystallise at different rates. One freeze–thaw cycle at most; aliquot before freezing rather than after.

How long does it keep once reconstituted? Honestly: nobody has published it

The original FDA label said the reconstituted solution “should be administered immediately” and any unused solution discarded — because the formulation carried no antimicrobial preservative. The European summary said “reconstituted immediately before use.” Those are the only regulator-reviewed statements that exist.

The 28-day refrigerated convention that circulates in this market reflects preservative efficacy and handling practice, not a stability study on this molecule. There is no published, ICH-format, multi-timepoint stability study on sermorelin anywhere in the accessible literature. We would rather say that than quote a confident number with nothing behind it.

Safety, and the shape of what is missing

Sermorelin's tolerability record is good. Its long-term safety record does not exist — and those are two different statements.

What the registration programme found

By the standards of the drugs it was competing with, that is a clean profile, and the 1999 review described the compound as well tolerated. Note one discrepancy: the label puts flushing under 1%, while the review calls transient facial flushing one of the two commonest events. We report the label figure as the numerical one.

Antibodies — the part the marketing never mentions

The Geref label states plainly: “A large proportion of patients develop anti-GRF antibodies at least once during treatment with Sermorelin.” The Lancet series puts a number on it — anti-GHRH antibodies in 14 of 18 prepubertal children, 78%.

In the studied populations and durations they did not reduce growth response, did not correlate with adverse reactions, and frequently reverted to negative at later assessments. That is the honest positive framing. The honest qualifier is that immunogenicity data exist only for children, treated for months to a few years, almost entirely before modern anti-drug-antibody assay standards. Nobody has looked at adults on chronic use.

The absence, stated as an absence

• There is no long-term adult safety dataset. This is not a gap in our research. It does not exist.
• The drug was approved for children, and withdrawn in 2009.
• The longest controlled adult exposure in the literature is six months.
• No adult trial measured cancer incidence, mortality, multi-year glucose tolerance or cardiovascular events. The 2018 review states explicitly that evaluation of cancer incidence and mortality with long-term secretagogue use is needed — meaning it has not been done.

Desensitisation

Continuous GHRH exposure desensitises the somatotroph, and it does so independently of running the GH pool down — it is a receptor-level effect. That is why every clinical protocol ever written used intermittent boluses, and why Marshall's continuous infusion did nothing while the same dose in four boluses worked.

With once-daily bolus dosing the picture is better: the Lancet series, over six to eighteen months, found no consistent evidence of priming or desensitisation. Whether the effect wanes over years has never been studied. The registration trial's fall from 8.0 to 7.2 cm/yr between six and twelve months is consistent with tachyphylaxis and also entirely consistent with catch-up growth completing; the paper does not attribute it, and neither will we.

Questions we actually get

Is sermorelin FDA approved?

It was, twice. It is not now, and has not been since 18 June 2009. The thing people mean when they say it is approved is usually tesamorelin, which is a different molecule and which does still hold a US approval.

But the FDA said it was safe, didn't they?

No. The FDA determined in 2013 that the products were not withdrawn for reasons of safety or effectiveness. That is a procedural finding about why the sponsor stopped selling it — it unblocks a generic application and nothing else. It is not a safety assessment, and no generic has been approved in the thirteen years since.

Is it on the FDA's do-not-compound list?

No — and this one gets overcorrected as often as it gets missed. Sermorelin appears in no 503A category at all. It sits in 503B Category 1, “under evaluation.” The 2023 listing that people are thinking of caught other growth-hormone-axis peptides, not this one.

Is it the same as CJC-1295 without DAC?

No. That is Mod GRF (1-29), which carries four substitutions — D-Ala², Gln⁸, Ala¹⁵, Leu²⁷. Sermorelin is the unmodified native sequence. They are about ten daltons apart and the difference is real: three of those four substitutions exist specifically to fix sermorelin's weaknesses.

Why is the half-life so short?

Because DPP-4 clips the first two residues off the front, and the resulting fragment has under a thousandth of the activity. Every later GHRH analogue is an attempt to protect that bond. Sermorelin is the unprotected original.

Didn't a big trial show GHRH improves cognition?

Yes, and it used tesamorelin, not sermorelin. Baker 2012 is quoted constantly as sermorelin evidence and it is not. There appears to be one controlled sermorelin cognition trial — Vitiello 2006, 89 adults, six months — and it has never been replicated.

How much water for a 5 mg vial?

2.5 mL gives 2 mg/mL, which is the cleanest arithmetic on a U-100 syringe. Anything from 1 to 5 mL dissolves without difficulty; solubility is not the constraint here.

How long does it last once reconstituted?

Nobody has published it. The original label said use immediately and discard the rest, because there was no preservative in the formulation. The 28-day refrigerated figure that circulates is a sterility convention, not a stability finding for this molecule. Keep it cold, keep it dark, and understand that the number is a convention.

Why does your certificate make such a fuss about content?

Because for this specific compound, content is where the market fails. In a survey of 6,285 samples across 203 manufacturers, sermorelin had the lowest median measured content of all fourteen peptides tested, and a quarter of samples came in under 89% of label. Purity was fine. The milligrams were not. Gross weighed powder is not peptide, and on a salt with six basic sites the gap runs to fifteen percent or more.

Is it banned in sport?

Yes, by name, at all times — WADA Prohibited List section S2.2.4, listed alongside CJC-1293, CJC-1295 and tesamorelin. Not just in competition.

So why do you carry it?

Because it is a well-characterised molecule with an unusually complete public record — two FDA approvals, registration-quality safety data, published head-to-head comparisons, a known degradation chemistry and a known failure mode. That makes it a good reference compound. It also makes it easy to be honest about, which is the part of this business we are actually in. What it is not is the thing the internet says it is.

References

1. Butenandt O, Staudt B. Comparison of growth hormone releasing hormone therapy and growth hormone therapy in growth hormone deficiency. Eur J Pediatr 1989;148(5):393–395. DOI 10.1007/BF00595894. PMID 2537727. — the paper this page turns on. Seven children, all acute responders, five of seven failed.
2. 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. DOI 10.1210/jcem.81.3.8772599. PMID 8772599. — the pivotal registration trial. Open label, no comparator.
3. 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. DOI 10.2165/00063030-199912020-00007. PMID 18031173. — the source of the dose-matched comparison against somatropin.
4. 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. DOI 10.1016/S0026-0495(97)90174-8. — 2 mg nightly, six weeks, no change in body composition.
5. Merriam GR, Barsness S, Buchner D, et al. Growth hormone releasing hormone treatment in normal aging. J Anti-Aging Med 2001;4(4). DOI 10.1089/10945450152850650. — the six-month programme. Lean mass up, visceral fat down — and sleep quality not improved.
6. Corpas E, Harman SM, Piñeyro MA, Roberson R, Blackman MR. Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. J Clin Endocrinol Metab 1992;75(2):530–535. DOI 10.1210/jcem.75.2.1379256. PMID 1379256. — fourteen days, hormones only. The origin of the “restores youthful levels” line.
7. Khorram O, Laughlin GA, Yen SSC. 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. DOI 10.1210/jcem.82.5.3943. PMID 9141536. — note the compound. It is the norleucine analogue, not sermorelin.
8. Arrigo T, Martino F, Lombardo F, et al. Diagnostic value of growth hormone-releasing hormone test in children and adolescents with idiopathic growth hormone deficiency. Eur J Pediatr 1992;151:263–265. DOI 10.1007/BF02072225. — 27 of 48 deficient children tested normal.
9. Ross R, Rodda C, Tsagarakis S, Davies P, Grossman A, et al. Treatment of growth-hormone deficiency with growth-hormone-releasing hormone. Lancet 1987;1(8523):5–8. — the source of the 14-of-18 antibody figure, and of the six non-responders.
10. Baker LD, Barsness SM, Borson S, Merriam GR, Friedman SD, Craft S, Vitiello MV. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults. Arch Neurol 2012;69(11):1420–1429. DOI 10.1001/archneurol.2012.1970. PMID 22869065. — tesamorelin, not sermorelin. Read the methods.
11. Vitiello MV, Moe KE, Merriam GR, Mazzoni G, Buchner DH, Schwartz RS. Growth hormone releasing hormone improves the cognition of healthy older adults. Neurobiol Aging 2006;27(2):318–323. DOI 10.1016/j.neurobiolaging.2005.01.010. PMID 16399214. — apparently the one sermorelin cognition trial. Never replicated.
12. Stewart CE, French KP, Wright TJ, et al. The effect of growth hormone-releasing hormone on cognition and brain connectivity in adults with cognition ranging from normal to mild cognitive impairment. eNeurologicalSci 2026;44:100616. PMID 42382101. — the most recent GHRH cognition trial. Tesamorelin, n = 22, null on primary measures.
13. Marshall L, Mölle M, Böschen G, Steiger A, Fehm HL, Born J. Greater efficacy of episodic than continuous growth hormone-releasing hormone administration in promoting slow-wave sleep. J Clin Endocrinol Metab 1996;81(3):1009–1013. DOI 10.1210/jcem.81.3.8772566. PMID 8772566. — the cleanest demonstration that continuous exposure desensitises.
14. Frohman LA, Downs TR, Williams TC, Heimer EP, Pan YC, Felix AM. 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. jci.org — the metabolite is fully immunoreactive and under a thousandth as active.
15. Frohman LA, Downs TR, Heimer EP, Felix AM. Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma. J Clin Invest 1989. jci.org — identifies DPP-4 by inhibitor rescue, and finds the second cleavage site.
16. Bongers J, Heimer EP, Lambros T, Pan YC, Campbell RM, Felix AM. Degradation of aspartic acid and asparagine residues in human growth hormone-releasing factor. Int J Pept Protein Res 1992;39(4):364–374. DOI 10.1111/j.1399-3011.1992.tb01596.x. PMID 1428526. — the deamidation and aspartimide chemistry, on this exact peptide family.
17. Sigalos JT, Pastuszak AW. The safety and efficacy of growth hormone secretagogues. Sex Med Rev 2018;6(1):45–53. DOI 10.1016/j.sxmr.2017.02.004. PMID 28400207. — “few long-term, rigorously controlled studies”; cancer and mortality evaluation still needed.
18. Sinha DK, Balasubramanian A, Tatem AJ, et al. Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Transl Androl Urol 2020;9(Suppl 2):S149–S159. DOI 10.21037/tau.2019.11.30. PMCID PMC7108996. — “no consistent fat loss” across the sermorelin studies.
19. Walker RF. Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? Clin Interv Aging 2006;1(4):307–308. PMID 18046908. PMCID PMC2699646. — an editorial. Two pages, no data. The most-cited reference in this compound's marketing.
20. Mendias CL, Awan TM. Evaluation of research grade peptides marketed directly to consumers reveals extensive variability in purity and measured abundance. Preprints.org 2026. DOI 10.20944/preprints202604.1748.v1. — 6,285 samples, 203 manufacturers. Sermorelin last of fourteen on measured content. A preprint, not yet peer-reviewed.
21. US Food and Drug Administration. Determination that GEREF (sermorelin acetate) injection was not withdrawn from sale for reasons of safety or effectiveness. Federal Register 78 FR 14095, 4 March 2013. Docket FDA-2012-P-1071. federalregister.gov — read the operative paragraph, not the summaries of it.
22. US Food and Drug Administration. Withdrawal of approval of 92 new drug applications and 49 abbreviated new drug applications. Federal Register 74 FR 23407, 19 May 2009. Effective 18 June 2009. — the withdrawal itself. Sponsor request, no longer marketed.
23. University of Maryland Center of Excellence in Regulatory Science and Innovation. Summary report: sermorelin acetate. Prepared for the US Food and Drug Administration, December 2020. — FDA-commissioned and neutral. Two qualifying clinical studies, both 1996, both Italian.
24. Health Canada. Unauthorized injectable peptide drugs seized and sold by Canada Peptide may pose serious health risks. Alert RA-77807, 1 August 2025. — sermorelin is named in the affected-products table.
25. World Anti-Doping Agency. The 2026 Prohibited List. In force 1 January 2026. Section S2.2.4, growth hormone releasing factors. — sermorelin named explicitly, prohibited at all times.
26. Geref (sermorelin acetate) for injection, US prescribing information; and Health Products Regulatory Authority (Ireland), Summary of Product Characteristics, GEREF 50, PA0285/006/001. — the source of the pharmacokinetics, the adverse-event rates, the antibody statement, the mannitol/phosphate formulation and the “protect from light” instruction.

Research-use compound. This page reports what the published literature and the regulatory record contain. It is not medical advice, it is not a protocol, and nothing on it should be read as a recommendation for use in humans.