Sermorelin

GRF 1-29, GHRH (1-29)-NH₂, sermorelin acetate; brand Geref (discontinued), Geref Diagnostic

Growth hormone axis

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Note on this profile. Sermorelin was an FDA-approved prescription medicine (Geref) for diagnosing and treating growth hormone deficiency in children from 1997 until the manufacturer withdrew it in 2008 for commercial reasons, not safety. Today it is available in the US through compounding pharmacies by prescription. Its use for "anti-ageing", body composition or sleep in adults without GH deficiency is off-label and not supported by approval.

Summary

Class: Synthetic peptide identical to the first 29 amino acids of human growth-hormone-releasing hormone (GHRH 1-44); the shortest fragment with full activity
Mechanism: Activates the pituitary GHRH receptor to stimulate synthesis and pulsatile release of the body's own growth hormone
Routes studied: Subcutaneous injection (treatment); intravenous bolus (diagnostic test)
Dose range reported: Approved paediatric dose (historical label): 30 µg/kg subcutaneous once daily at bedtime. Diagnostic: 1 µg/kg IV. Adult studies: 0.5–2 mg/day subcutaneous (e.g. 2 mg nightly in older adults for 6–16 weeks). Compounded adult prescriptions and community reports: 200–500 µg nightly, sometimes 1 mg. Off-label in adults
Half-life: ~10–20 minutes in plasma; GH peak at about 30–60 minutes after injection
Storage: Lyophilised: refrigerate (2–8 °C). Reconstituted: refrigerate; the original label allowed 14 days after reconstitution with bacteriostatic water; community practice is up to ~4 weeks
Regulatory status: Formerly FDA-approved (withdrawn 2008 for non-safety reasons); available by prescription via compounding in the US. Not approved in most other regions

Doses are as reported in studies or by the community — never recommendations.

1What it is

Sermorelin is simply the business end of GHRH, the hormone the hypothalamus releases to prompt the pituitary to make growth hormone. The first 29 of GHRH's 44 amino acids are enough for full activity, and that fragment was synthesised in the 1980s following the isolation of GHRH from pancreatic tumours by Guillemin's and Vale's groups in 1982. Serono developed it as Geref: a diagnostic injection to test pituitary function, and a daily treatment for children with growth failure due to inadequate GHRH. It was approved in the US in 1997, and was withdrawn in 2008 when EMD Serono discontinued it commercially, with recombinant GH having taken over the paediatric market.

Because it had been approved, its bulk substance remained eligible for pharmacy compounding, and sermorelin has become the GH-axis compound most often prescribed by US "longevity" and men's-health clinics. It is a real medicine with a real safety history in children; the adult anti-ageing use rests on far thinner evidence.

2How it's thought to work

Sermorelin binds the GHRH receptor on pituitary somatotrophs, raising cyclic AMP, which both stimulates immediate GH release and increases GH gene expression over time. Because it works upstream of the pituitary:

GH is released in a pulse that still answers to the body's own feedback (somatostatin, IGF-1), so the risk of runaway GH excess is lower than with injected GH.

It requires a functioning pituitary — it does nothing in pituitary GH deficiency, which is why it was used as a diagnostic test to distinguish hypothalamic from pituitary causes.

Given at bedtime it amplifies the natural nocturnal GH surge.

Combining with a ghrelin-receptor (GHRP) produces a larger GH pulse than either alone.

A GHRH analogue: the pituitary releases the body's own growth hormone in pulses, and the liver answers with IGF-1.Schematic — not to scale

3What the research shows

Paediatric GH deficiency / idiopathic short stature

Daily 30 µg/kg sermorelin increased growth velocity in children with GH deficiency of hypothalamic origin in controlled trials, though less than recombinant GH, and roughly half to two-thirds of children responded (Thorner 1996, J Clin Endocrinol Metab — 12-month trial; label data). This is the basis of the former approval. [1]

Diagnostic GH stimulation

IV sermorelin 1 µg/kg was a validated pituitary stimulation test, usually combined with arginine. Still described in endocrinology references though the product is unavailable in many places.

Graded A/B (small)

Older adults

Studies in healthy older men and women given 1–2 mg nightly for 6 to 16 weeks increased GH and IGF-1 toward young-adult levels, with modest increases in lean body mass and skin thickness, some increase in insulin resistance, and little change in strength or function (Corpas 1992, J Clin Endocrinol Metab; Vittone 1997, Metabolism; Khorram 1997, J Clin Endocrinol Metab). Sample sizes were in the tens. Long-term outcome trials do not exist. [2][3][4]

Sleep

Small studies of GHRH in young and older men reported more slow-wave sleep after bolus GHRH, consistent with GHRH's known sleep-promoting role (Steiger 1992, Neuroendocrinology). Community reports of better sleep have a plausible basis but no large trial. [7]

Graded B (sermorelin); A for the related analogue tesamorelin

HIV lipodystrophy

Sermorelin itself was tested in small studies in HIV-associated fat accumulation with modest visceral-fat changes; tesamorelin took this indication to approval.

Graded — / B

Body composition and "anti-ageing" in middle-aged adults

Clinic use is extensive; published controlled data in this population are essentially the small older-adult studies above. Claims about longevity, cognition or recovery are unsupported.

4Reported side effects and interactions

Literature-reported

Literature (paediatric label and adult studies). injection-site reactions (pain, redness, swelling — the most common, around 1 in 6 children), facial flushing, headache, dizziness, nausea, hyperactivity, somnolence, dysphagia and taste changes were listed; antibodies to GHRH developed in some children without apparent clinical effect. In older adults: fluid retention, arthralgia, carpal-tunnel-type symptoms and raised fasting glucose/insulin at 2 mg/day, consistent with GH action.

Community-reported

flushing and warmth after injection, headache, water retention, tingling in hands, increased hunger, vivid dreams or grogginess on waking, injection-site lumps.

Class-level considerations from GH physiology. reduced insulin sensitivity, joint pain, oedema, theoretical concern in active malignancy. These are the recognised risks of raising GH/IGF-1 by any method; sermorelin's feedback-respecting mechanism likely reduces but does not remove them.

Interactions. glucocorticoids, levodopa, insulin, clonidine and cyclooxygenase inhibitors interfere with the diagnostic GH response (listed in the former label); thyroid hormone should be replaced before testing. Additive with GHRPs.

Markers researchers commonly monitor

Marker	Why it's watched
IGF-1	the standard marker of GH-axis response; clinics typically aim to keep it within the age-adjusted reference range. Measured at baseline and after 4–12 weeks.
IGFBP-3	sometimes measured with IGF-1.
Fasting glucose, fasting insulin, HbA1c	insulin resistance rose in the 2 mg/day older-adult studies.
Thyroid function (TSH, free T4)	thyroid status affects the GH response and should be normal before interpreting IGF-1.
Prolactin	not expected to rise with sermorelin; useful to distinguish from GHRP effects in combinations.
Body composition (DEXA) and waist circumference	the outcomes the adult studies measured.
Blood pressure, oedema, joint and wrist symptoms	practical signs of GH excess.
General baseline CBC, CMP, lipids

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Compounded and research vials are commonly 2 mg, 5 mg, 9 mg or 15 mg (multi-dose). with , swirl gently, refrigerate. The original Geref label specified use within 14 days of reconstitution; many compounders now state 28 days. Typically injected subcutaneously at bedtime on an empty stomach, as reported in studies and clinic protocols.

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6Commonly studied alongside

Ipamorelin, GHRP-2, GHRP-6 (synergistic GH release), arginine (diagnostic test), tesamorelin and CJC-1295 (as alternatives). Compounded "sermorelin/ipamorelin" combinations are common in US clinics.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Approved 1997 (Geref, Geref Diagnostic); withdrawn 2008 for commercial reasons. Sermorelin acetate remains available through compounding pharmacies by prescription; it is not on the FDA's 2023 Category 2 list †
European Union	Not currently authorised †; GHRH diagnostic products were previously available in some member states
United Kingdom	Not licensed
Australia	Not an approved product; GHRH analogues are prescription-only (Schedule 4)
South Africa	Not registered
Sport	Prohibited by WADA (S2 — GHRH and its analogues are named)

8Open questions

Does restoring GH pulses in otherwise healthy middle-aged adults improve any hard outcome? The older-adult studies improved IGF-1 and body composition modestly without functional gains.
Long-term safety of chronic GHRH stimulation in adults — unstudied beyond a few months.
Does antibody formation (seen in children) matter with years of adult use?
Is the sermorelin compounded in clinics consistently potent and sterile? Compounding quality varies.

9References

1Thorner M et al. (1996). Growth hormone (GH) releasing hormone (GHRH) 1-29 treatment of GH-deficient children: 12-month results. J Clin Endocrinol Metab. PubMed
2Corpas E, Harman SM, Piñeyro MA, Roberson R, Blackman MR (1992). 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. PubMed · DOI
3Khorram O, Laughlin GA, Yen SSC (1997). 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. PubMed · DOI
4Vittone J et al. (1997). Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism. PubMed · DOI
5Walker RF (2006). Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? Clin Interv Aging. PubMed · DOI
6Prakash A, Goa KL (1999). Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs. PubMed · DOI
7Steiger A et al. (1992). Effects of growth hormone-releasing hormone and somatostatin on sleep EEG and nocturnal hormone secretion in male controls. Neuroendocrinology. PubMed · DOI
8Geref (sermorelin acetate for injection) prescribing information, EMD Serono (historical label). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

25 Oct 2026Profile published — awaiting medical review

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