Peptide Health Lab

Growth hormone axis

Sermorelin

Also known as: GHRH(1-29)NH2, Sermorelin acetate, Geref

Regulatory status
Rx via compounding
Evidence grade
Anecdotal reports only

Last reviewed September 1, 2026 · 10 sources

What sermorelin is and how it works

Sermorelin is the first 29 amino acids of human growth-hormone-releasing hormone, with an amide group at the C-terminus — GHRH(1-29)NH2. That fragment is the shortest synthetic peptide retaining the full biological activity of the 44-residue natural hormone, which is the entire design rationale: everything past residue 29 turned out to be dispensable for receptor activation.[8] When investigators compared the response to GRF(1-40) against GRF(1-29)NH2 in eleven young adult volunteers, the results were identical.[2]

Given intravenously or subcutaneously, sermorelin binds the GHRH receptor on pituitary somatotropes and specifically stimulates growth hormone release. The pharmacokinetics are the interesting part and they explain both the drug's diagnostic usefulness and its therapeutic limits. Sermorelin is eliminated rapidly after intravenous injection, yet growth hormone stays elevated for about three hours, and the lowest tested dose of 0.25 micrograms per kilogram already released a significant amount of it. Maximal release came at 1 to 2 micrograms per kilogram.[4] Because the pituitary does the releasing, the resulting secretion keeps its own pulsatile character rather than becoming a flat elevation — the property that distinguishes a secretagogue from administering growth hormone itself.

That mechanism carries a hard boundary, and it is the same boundary that applies to every compound in this class. Sermorelin only works if there is a pituitary capable of responding. In deficiency of pituitary origin, there is nothing to stimulate. This is why a normal growth hormone response to sermorelin cannot exclude growth hormone deficiency: a hypothalamic deficit produces a normal pituitary response to a direct GHRH signal, and confirming disease in those patients requires a subnormal response to other provocative tests.[8]

Sermorelin has a regulatory history that shapes how the evidence below should be read. It was an approved US drug in two forms — a diagnostic ampule and a treatment vial — and both approvals were withdrawn in 2009 at the sponsor's own request. The published literature is what was generated for those two approvals, which is to say it is pediatric and diagnostic. It is not literature about the use sermorelin is now most often discussed for.

What the research actually shows

Diagnostic testing is the best-evidenced use. A single intravenous dose of 1 microgram per kilogram produces a rapid and relatively specific growth hormone response. In 131 children and adolescents, 45 of them with idiopathic growth hormone deficiency, a maximal growth hormone level above 10 ng/mL during the 120-minute test period was found to be normal; three of 86 children without deficiency fell below that threshold and eleven of 45 with deficiency exceeded it.[2] Fewer false-positive growth hormone responses occur in children without deficiency after sermorelin than after other provocative tests, and adult data suggest combining it with arginine is more specific still.[8] The diagnostic use of GHRH in short stature was described in the mid-1980s alongside its therapeutic possibilities.[1]

Pediatric growth treatment worked, and the comparison against growth hormone is reported less carefully than it should be. Once-daily subcutaneous sermorelin at 30 micrograms per kilogram at bedtime produced significant, sustained increases in height velocity over 12 months in some prepubertal children with idiopathic growth hormone deficiency, with catch-up growth in the majority and data in a few children suggesting the effect held for 36 months. Slower-growing, shorter children with delayed bone and height age responded best. The review that summarizes this evidence also says, in as many words, that the effects of the recommended dosage of sermorelin have not been directly compared with those of somatropin. The comparison it does report is a different one, and the schedules do not match: increases in height velocity were smaller with subcutaneous sermorelin at 30 micrograms per kilogram per day given as a continuous infusion or as three divided doses than in children receiving once-daily subcutaneous somatropin at the same weight-based dose. Neither of those sermorelin regimens is the once-daily bedtime schedule the review recommends. The effect of long-term treatment on final adult height was never determined.[8]

The head-to-head evidence sits in a separate randomized study. Sixty children with proven growth hormone deficiency of hypothalamic origin were randomized to GHRH(1-29)NH2 at 30 or 60 micrograms per kilogram per day or to growth hormone at 0.1 IU per kilogram per day for six months. Mean height velocities at six months were 9.2, 9.3, and 14.6 centimetres per year: growth on growth hormone was significantly better than on either GHRH dose, and there was no difference between the two GHRH doses. Nearly every child on GHRH developed anti-GHRH antibodies, which had almost disappeared nine months after stopping. The GHRH here was given by continuous infusion, and the authors concluded that this route, or a depot preparation, is unlikely to match growth hormone for promoting growth.[6]

In healthy older men, two small studies, and they disagree in an instructive way. Ten healthy old men aged 68 on average received both 0.5 mg and 1 mg subcutaneously twice daily for 14 days, in randomized order with a washout. At the high dose — and only at the high dose — mean 24-hour growth hormone, area under the growth hormone peaks, peak amplitude, and IGF-1 all rose significantly, to values no longer distinguishable from those of young men. Fasting glucose, urinary C-peptide, blood pressure, and chemistry panels were unaffected.[3] A separate study gave eleven men aged 64 to 76 a single nightly 2 mg injection for six weeks. Nocturnal growth hormone release, area under the peak, and peak amplitude rose — and IGF-1, IGF binding protein-3, and growth hormone binding protein did not change at all. Neither did weight, body-mass index, waist-to-hip ratio, muscle and fat on dual-energy x-ray absorptiometry, muscle histology, glucose, insulin, or lipids. Two of six strength measures and one endurance measure improved. The authors concluded that single nightly dosing is less effective than multiple daily dosing at producing growth-hormone-mediated effects.[7]

Intranasal delivery was tried and did not survive contact with the data. Nasal bioavailability was 3 to 5%, so roughly fifty times the intravenous dose was needed for an equivalent response.[4] In a six-month pilot of eight short prepubertal children given intranasal sermorelin three times daily, growth hormone peak amplitudes were variably reduced at six weeks and further reduced at six months, anti-GHRH antibodies appeared in three patients who had started negative, mean six-month height velocity did not increase, and most children reported sneezing, rhinorrhea, and mucosal burning. Two stopped treatment. The investigators concluded the route was not suitable in that form.[5]

Where the evidence is weak

The published evidence and the modern use case are about different people. This is the page. Sermorelin's human literature is prepubertal children with idiopathic growth hormone deficiency, plus pituitary diagnostic testing, plus two short physiological studies in healthy older men. The use it is discussed for today is adult anti-aging, sleep, recovery, and body composition. No published trial has evaluated any of those outcomes. Not a negative trial — no trial. The strongest published statement about adult effects is a fourteen-day crossover study's closing suggestion that prolonged treatment could improve age-related body-composition changes, which is a hypothesis its authors offered in 1992 and which nobody subsequently tested.[3] This gap is also why the compound-level evidence grade on this page reads lower than the grades on individual claims above. Sermorelin has genuine randomized human evidence — for diagnostic pituitary testing and for growing prepubertal children with a diagnosed deficiency. The grade at the top of the page reflects the claim people actually arrive with, and that claim has none.

The one adult study that measured body composition found nothing. The six-week nightly-injection study is the closest thing to a test of the modern claim, and it reported no change in weight, body-mass index, waist-to-hip ratio, muscle or fat on imaging, muscle histology, glucose, insulin, or lipids. Its positive findings were two of six strength measures and one endurance measure in eleven uncontrolled subjects — a result the authors themselves framed as suggesting an optimized regimen might help, not as a demonstration.[7]

The literature is old and small. The substantive human work dates from the mid-1980s to the late 1990s and was generated for a drug that left the market. Nothing has replaced it. Sample sizes are in the tens, not the hundreds, and the adult work is uncontrolled or crossover rather than placebo-controlled with a clinical endpoint.

Immunogenicity is a real and under-examined signal. Three of eight children developed anti-GHRH antibodies within six weeks of repeated intranasal administration, alongside falling responses.[5] Whether repeated subcutaneous administration in adults over months produces the same thing has not been studied. For a compound whose entire proposition is repeated administration, that is a conspicuous gap.

The schedule dependency is unresolved and matters. Twice-daily dosing raised IGF-1; once-nightly dosing did not raise it at all.[3][7] Since IGF-1 is the mediator of most downstream growth hormone effects, a schedule that raises growth hormone without raising IGF-1 may not be doing much of anything. No study has resolved which schedule, if any, produces a clinical result in adults.

The mechanism's known associations have not been examined here. Raising growth hormone and IGF-1 is what sermorelin does. Growth hormone opposes insulin action, and large prospective cohorts link higher circulating IGF-1 to the risk of several cancers, most consistently prostate cancer, in people taking nothing.[9][10] The sermorelin studies were far too short and too small to detect anything of that kind. That is an absence of data, not a demonstration of safety.

Legal and regulatory status

Sermorelin is not currently an FDA-approved drug, and this is the single regulatory fact most often stated incorrectly about it. It was approved twice. Geref (sermorelin acetate) injection at 0.05 mg base per ampule was approved under NDA 19-863 on December 28, 1990, indicated for evaluating the ability of the pituitary somatotroph to secrete growth hormone. Geref injection at 0.5 mg and 1.0 mg base per vial was approved under NDA 20-443 on September 26, 1997, indicated for the treatment of idiopathic growth hormone deficiency in children with growth failure. Both indications track what the clinical literature described for the compound at the time: a relatively specific provocative test of growth hormone secretion given as a single intravenous dose, and once-daily subcutaneous treatment effective in promoting growth in some prepubertal children with idiopathic growth hormone deficiency.[8]

The sponsor discontinued both products in 2008 and asked FDA to withdraw both applications. FDA withdrew approval of NDA 19-863 and NDA 20-443 effective June 18, 2009. In 2013, responding to a citizen petition and acting on its own initiative for the second product, FDA determined that neither had been withdrawn from sale for reasons of safety or effectiveness — a determination that keeps them listed in the Discontinued Drug Product List section of the Orange Book and permits abbreviated new drug applications referencing them. No such application has produced a marketed product.

Two things follow, and they pull in opposite directions. A withdrawn approval is not a current approval: sermorelin cannot be badged FDA-approved, because no approved sermorelin product is marketed in the United States today. But the withdrawal was commercial rather than a safety action, which is a materially different history from a compound that was never approved at all, and it is why this page is not framed as research-only.

What exists today is compounded sermorelin, prepared by pharmacies and dispensed on a prescription. That is a regulatory description of the compound's status and nothing more. Sermorelin acetate does not appear on FDA's list of bulk drug substances that can be used in compounding under section 503A, nor in any of the three interim-policy categories the agency maintains for nominated substances — it is not under evaluation, not flagged as raising significant safety risks, and not listed as nominated without adequate support. Its availability rests instead on having been a component of an approved drug product, a prong whose application to a withdrawn approval is not a settled question. A compounded preparation is by definition not an approved product: no approved labeling, no manufacturer safety surveillance, no post-marketing adverse-event programme.

A prescription is required, which means a licensed prescriber evaluates whether it is appropriate, sets and adjusts the dose against laboratory monitoring, and follows the response. Peptide Health Lab does not sell peptides, does not prescribe, and does not tell anyone where to obtain anything. Athletes in tested sport should note that growth-hormone-releasing hormone analogs as a class are prohibited at all times under the World Anti-Doping Agency's rules, and should confirm the current year's list rather than rely on a static page.

Questions to bring to a provider

The gap between what sermorelin has been studied for and what it is prescribed for is wide enough that the questions almost write themselves:

  • Is there a reason to think the growth hormone axis is abnormal here, and what testing would establish that rather than assume it from a symptom list?[2]
  • Given that the published human evidence is pediatric growth treatment and diagnostic testing, what evidence supports the outcome being sought here?[8]
  • If the goal is body composition or strength, how should the six-week adult study that found no change in weight, muscle, fat, glucose, or lipids be weighed?[7]
  • Since twice-daily dosing raised IGF-1 and once-nightly dosing did not, what schedule is intended and what result would show it is working?[3]
  • What baseline and follow-up laboratory monitoring — IGF-1, glucose — is planned, and at what interval?[3]
  • Does a personal or family history of malignancy change the calculus, given the cohort associations between circulating IGF-1 and cancer risk?[10]
  • For a compounded preparation, what beyond-use date and handling instructions come with it, given that no approved labeling exists?[8]

A clinician who says "this was a pediatric drug that left the market, and the adult use has never been tested" is describing the record accurately.

Evidence by claim

Grades describe how strong the evidence is; the line under each grade describes what kind of studies it is. How we grade evidence.

Diagnostic testing of pituitary growth hormone secretory capacity
Human RCT evidence human observational · review

This is sermorelin's best-evidenced use and the one an approved product existed for. A single 1 microgram per kilogram intravenous dose produces a rapid and relatively specific growth hormone response; in 131 children and adolescents, a maximal growth hormone level above 10 ng/mL characterized a normal response, and the responses to GRF(1-40) and GRF(1-29)NH2 were identical in adult volunteers. Fewer false-positive responses occur in children without deficiency than with other provocative tests. The test's limitation is structural: a normal response cannot exclude deficiency of hypothalamic origin.

[2] [8] [1]

Promoting growth in prepubertal children with idiopathic growth hormone deficiency
Human RCT evidence review · human RCT

Supported, and modest. Once-daily subcutaneous sermorelin at 30 micrograms per kilogram at bedtime produced sustained increases in height velocity over 12 months, with catch-up growth in the majority of treated children and data in a few suggesting maintenance to 36 months. The review is explicit that this recommended regimen was never directly compared with somatropin. The comparison it does report is not schedule-matched: height velocity rose less with sermorelin at 30 micrograms per kilogram per day given as a continuous infusion or in three divided doses than in children receiving once-daily subcutaneous somatropin at the same weight-based dose. The head-to-head evidence comes instead from a separate randomized study of 60 children, in which growth on growth hormone was significantly better than on GHRH(1-29)NH2 at either of two doses — mean height velocities of 14.6 against 9.2 and 9.3 centimetres per year at six months. The effect of long-term sermorelin treatment on final adult height was never determined.

[8] [6]

Raising growth hormone and IGF-1 in healthy older adults
Human RCT evidence human RCT · human observational

Demonstrated, in one small study, with a schedule dependency. Ten healthy old men received both 0.5 mg and 1 mg subcutaneously twice daily for 14 days in randomized order. The high dose significantly raised mean 24-hour growth hormone, area under the growth hormone peaks, peak amplitude, and IGF-1, to the point that these no longer differed from young men. The low dose did not. A separate six-week study using a single nightly 2 mg injection raised nocturnal growth hormone but did not change IGF-1 at all. The authors of the first study framed their result as a suggestion that prolonged treatment could improve age-related body-composition changes — a hypothesis, and one that was not subsequently tested.

[3] [7]

Body composition, strength, or functional benefit in healthy adults
Anecdotal reports only human observational · human RCT

Essentially unstudied, and what little exists is thin. The six-week nightly study in eleven healthy men aged 64 to 76 measured this directly and found no change in weight, body-mass index, waist-to-hip ratio, dual-energy x-ray absorptiometry measures of muscle and fat, muscle histology, glucose, insulin, or lipids. Two of six strength measures and one endurance measure improved, in eleven uncontrolled subjects over six weeks, which the authors themselves presented as a suggestion that an optimized regimen might attenuate some effects of aging. No randomized controlled trial has tested a functional or body-composition outcome of sermorelin in adults.

[7] [3]

Anti-aging benefit, or any benefit in an adult without growth hormone deficiency
Anecdotal reports only human observational · review

No published human evidence exists. This is the use sermorelin is most discussed for today and the use the literature has least to say about. What is published is pediatric growth treatment, diagnostic testing, and two short physiological studies in older men that measured hormones and, in one case, a handful of strength tests. There is no trial of sermorelin with an anti-aging, longevity, sleep, recovery, or body-composition endpoint in adults. That absence is stated here as a finding, because it is one.

[7] [8]

Intranasal administration as a practical route
Anecdotal reports only human RCT · human observational

Tested and abandoned, on thin evidence. The finding that decides the question is an eight-child open-label pilot, not a randomized trial; the controlled pharmacokinetic work established only that the route delivers very little. Nasal bioavailability was only 3–5% in healthy men, requiring roughly fifty times the intravenous dose. In a six-month pilot in eight short prepubertal children given intranasal sermorelin three times daily, growth hormone peak amplitudes fell progressively, anti-GHRH antibodies appeared in three of eight, mean stadiometric height velocity did not increase over six months, and local reactions were common. The investigators concluded the route was not suitable in that form.

[4] [5]

Typical protocol range in the research

  • Diagnostic pituitary testing in children and adolescents, the use the withdrawn 0.05 mg presentation was approved for; 131 children and adolescents including 45 with idiopathic growth hormone deficiency were tested in one such study

    A single intravenous dose of 1 microgram per kilogram of body weight, with maximal growth hormone during the following 120 minutes as the measured response [2]

  • Dose-ranging in 30 healthy men aged 19–43, comparing intravenous and intranasal administration

    Intravenously, 0.25 micrograms per kilogram was the lowest dose that released growth hormone significantly and 1–2 micrograms per kilogram produced the maximal response; intranasal bioavailability was only 3–5%, so about 50 micrograms per kilogram intranasally was needed to match 1 microgram per kilogram intravenously [4]

  • Treatment of prepubertal children with idiopathic growth hormone deficiency, the use the withdrawn 0.5 and 1 mg presentations were approved for

    30 micrograms per kilogram of body weight once daily by subcutaneous injection at bedtime, sustained over 12 months and in a few children over 36 months [8]

  • Short-term treatment of healthy older men — the only published randomized-order human work in anything resembling the adult population sermorelin is now discussed for

    0.5 mg and 1 mg subcutaneously twice daily for 14 days in one crossover study, and 2 mg subcutaneously once nightly for six weeks in another [3] [7]

Two of the four ranges above come from a withdrawn approved product's pediatric and diagnostic indications, and two come from short physiological studies in older men that measured hormone levels and, in one case, muscle strength. None of them establishes a dose of sermorelin for adult anti-aging use, because no published trial has evaluated that use. A compounded preparation's dose is set by the prescriber who wrote for it, against laboratory monitoring, and is not something this page can or should supply.

Ranges are what published research reports, not a recommendation. PHL does not prescribe, and nothing here is personalized to you.

Side effects & safety signals

  • Injection-site reactions and transient facial flushing

    The most commonly reported adverse events in the pediatric review of both single intravenous doses and repeated once-daily subcutaneous dosing. · Mild and self-limiting in the published record, and the reason the drug was characterized as well tolerated in the population where it was studied. Flushing is the expected vasomotor effect of a growth-hormone-releasing hormone analog.

    [8]

  • Anti-GHRH antibody formation with loss of effect

    Antibodies, initially negative, became positive in three of eight children after six weeks of intranasal administration in a pilot study. · This is the most interesting safety signal in the sermorelin literature and the least discussed. Peak growth hormone amplitudes fell progressively over six months, height velocity did not increase, and treatment was stopped in two patients. The investigators concluded that intranasal administration in that form was not suitable for children because of decreasing absorption and effectiveness alongside antibody development and local reactions. Whether repeated subcutaneous administration in adults carries the same immunogenicity has not been studied.

    [5]

  • Effect on growth hormone secretion is not sustained by all schedules

    Observed as a difference between dosing frequencies rather than as an adverse event. · A six-week study of single nightly injections in healthy elderly men raised nocturnal growth hormone release but produced no change in IGF-1, IGF binding protein-3, growth hormone binding protein, weight, body-mass index, dual-energy x-ray absorptiometry measures of muscle and fat, muscle histology, glucose, insulin, or lipids. The authors concluded that single nightly dosing is less effective than multiple daily dosing at eliciting growth-hormone-mediated effects. A schedule that raises the hormone without moving anything downstream is a real finding about this compound.

    [7]

  • Long-term safety in adults, and safety of any compounded preparation

    Not established · The longest published human exposures are 36 months in a small number of children and six weeks in healthy older men. No published study has followed an adult on sermorelin for anti-aging purposes for any length of time. Separately, a compounded preparation is not an approved product: it has no approved labeling, no manufacturer safety surveillance, and no post-marketing adverse-event programme behind it. That is a structural difference from an approved drug rather than a claim that any particular preparation is unsafe.

    [8] [7]

  • Growth-hormone-axis effects generally, including glucose and IGF-1 exposure

    Not observed in the sermorelin studies themselves — the 14-day crossover study in older men found no effect on fasting glucose, urinary C-peptide, blood pressure, or chemistry and hematology panels. · The mechanism is to raise growth hormone and IGF-1, and both are variables with known associations. Growth hormone opposes insulin action; large prospective cohorts link higher circulating IGF-1 to the risk of several cancers, most consistently prostate cancer, in people taking nothing. The sermorelin studies were too short and too small to detect anything of that kind, which is different from having ruled it out. Existing diabetes or prediabetes, and a personal or family history of malignancy, are provider-discussion flags before anything is considered.

    [3] [9] [10]

Published lists are never exhaustive, so report anything unexpected to a licensed provider.

Storage, handling & reconstitution

Lyophilized storage
Sermorelin is supplied as a lyophilized powder and is conventionally kept refrigerated at 2–8 °C and protected from light. Because no approved sermorelin product is currently marketed in the United States, there is no manufacturer stability programme and no assigned expiry date standing behind material bearing the name today. A compounded preparation carries whatever beyond-use date the compounding pharmacy assigned it under its own standards, which is a real answer rather than a convention — and it is an answer that comes from the dispensing pharmacy, not from this page.
Reconstituted storage
Once in solution, peptide preparations are conventionally refrigerated at 2–8 °C, protected from light, and treated as short-dated rather than indefinitely stable. The published sermorelin literature concerns its pharmacokinetics in circulation — it is eliminated rapidly after intravenous injection while growth hormone stays elevated for about three hours — and says nothing about shelf life in a vial. A compounded preparation's in-use window is assigned by the pharmacy that prepared it.
Reconstitution diluent
The conventional diluent for a lyophilized peptide preparation is bacteriostatic water: sterile water preserved with 0.9% benzyl alcohol. Sterile water without a preservative is used where a preservative is contraindicated and is treated as single-use. For a compounded sermorelin preparation, the diluent and the in-use window are specified by the compounding pharmacy that dispensed it.
Reconstitution & handling
Conventional handling: sanitize the stopper before piercing it, add the diluent slowly down the inside wall of the vial rather than directly onto the powder, and let it dissolve on its own. Swirl gently if needed; never shake. A properly reconstituted solution is clear; anything cloudy, discolored, or carrying visible particulate is discarded. PHL does not publish volume or unit calculations, because those are dosing decisions and dosing decisions belong with a licensed clinician.
Handling notes
The gap between an approved product and a compounded one is the whole story for sermorelin storage. The withdrawn Geref products had labeling; nothing marketed today does. What replaces that labeling is the compounding pharmacy's own beyond-use dating and the prescriber's instructions, and those are patient-specific documents rather than public information.

The how-to guides cover the conventions behind these fields, and what the published stability data does and does not establish: Storage, Reconstitution, Handling.

Questions for your provider

Bring this page to a licensed provider. A provider can order labs, review your medications and history, and tell you whether anything here is relevant to your situation. This page can't. Peptide Health Lab does not prescribe and does not sell peptides.

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Citations

10 sources · every identifier checked against PubMed

Before you act on any of this

This page is educational only and is not medical advice. It does not diagnose, treat, or prescribe. Review it with a licensed provider before making any health decision. Peptide Health Lab does not sell peptides.

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