GHRH receptor agonist (short-acting)
Sermorelin
GHRH(1-29)NH2 — the biologically active N-terminal fragment of endogenous GHRH
Overview
Sermorelin is the 29-amino-acid N-terminal fragment of endogenous growth hormone-releasing hormone (GHRH), retaining full biological activity at the pituitary GHRH receptor. It is the shortest sequence that binds and activates the receptor efficiently. Its half-life is very short (~10–20 minutes), which means the GH response is a discrete pulse rather than a sustained elevation.
Historically, sermorelin acetate was FDA-approved as Geref in 1990 for the treatment of pediatric growth hormone deficiency. The NDA was withdrawn from the U.S. market by the sponsor in 2008 for commercial reasons — this was not a safety-related withdrawal. Modern access in the United States is exclusively via compounding pharmacies; there is no currently marketed FDA-approved sermorelin product.
Compared with tesamorelin (the longer, stabilised GHRH(1-44) analogue with documented visceral-fat-reduction pharmacology in the peer-reviewed literature), sermorelin produces a shorter, sharper GH pulse. Its editorial framing on Healthy Mango is research-only.
Quick Facts & Evidence
- Category
- GHRH receptor agonist (short-acting)
- Research area
- GHRH analogue
- Most studied for
- Pediatric growth hormone deficiency (historical FDA indication)
- Adult growth hormone deficiency (historical trial data)
- Sleep quality and body composition in aging populations (off-label; limited data)
- Clinical status
- Established clinical use
- Human evidence
- Moderate Human Evidence
- Regulatory status
- Not approved by FDA, EMA or MHRA
Moderate Human Evidence
Supported by human trials, but of limited size, duration, or replication. May be approved for related but not identical indications.
Research Protocols
Research Protocol Snapshot
Preparation covered on this page
Freeze-dried injectable research format
This page covers the RUO lyophilized sermorelin vial reconstituted with bacteriostatic water for subcutaneous research use, following the standard Healthy Mango preparation convention.
Sermorelin research values at a glance.
| Item | Example value |
|---|---|
| Vial size | 10 mg |
| Liquid used to mix | Bacteriostatic water |
| Amount of liquid added | 2.0 mL |
| Final concentration | 5 mg/mL |
| How it's given | Subcutaneous injection |
| Research dose | 0.2–0.3 mg (200–300 mcg) per pulse |
| Frequency | Daily, pre-sleep, fasted |
| After mixing | Refrigerate; use within 7–10 days |
Reported Dosing
The practitioner-reference research protocol for sermorelin is 0.2–0.3 mg per subcutaneous pulse, daily, pre-sleep and fasted, across a 3-month cycle. It is educational reference, not a recommendation.
The Reported Protocol
| Dose | Frequency | Duration | Notes |
|---|---|---|---|
| 0.2–0.3 mg | Daily, pre-sleep, fasted, subcutaneous | 3 months on / 1 month off | 0.04–0.06 mL at 5 mg/mL |
Why protocols vary
Sermorelin's ~10–20 minute plasma half-life produces a short, sharp physiologic GH pulse rather than a sustained elevation. Pre-sleep fasted dosing aligns the pharmacologic pulse with the body's own overnight GH release and avoids carbohydrate blunting of the same pulse.
The 3-month-on / 1-month-off cadence prevents pituitary receptor desensitisation over long-term use, a general concern with sustained GHRH-analogue exposure. Historical clinical use in pediatric GHD (Thorner 1996) ran continuously in the approved Geref era; that trial context is not the practitioner-reference cadence above.
Preparing the Solution
Turning the freeze-dried powder into a measurable liquid.
Documented preparation
The documented research protocol is based on this preparation concentration.
Freeze-dried powder: 10 mg vial
Diluent: 2.0 mL bacteriostatic water
Final concentration: 5 mg/mL
Vial and volume from the practitioner reference; concentration calculated · Research-practitioner guide
Your vial
Matching preparation
Bacteriostatic water
2mL
Resulting concentration
5 mg/mL
Equivalent volume
The reported research amount of 0.20–0.30 mg is contained within
0.04–0.06mL
of the prepared solution now in your vial.
Show calculation
- Documented concentration
- 10 mg ÷ 2 mL = 5 mg/mL
- Bacteriostatic water to match the documented concentration
- 10 mg ÷ 5 mg/mL = 2 mL
- Equivalent volume at this concentration
- 0.20–0.30 mg ÷ 5 mg/mL = 0.04–0.06 mL
This tool performs arithmetic conversions using the preparation example and reported research amount shown on this page. It does not recommend an amount, route, preparation method, or use.
This tool performs arithmetic conversions using the preparation example and reported research amount shown on this page. It does not recommend an amount, route, preparation method, or use.Sources for these values
- Documented in the practitioner referenceResearch-practitioner guide
This example explains how concentration and volume are calculated for the standard RUO preparation. It is not a preparation guide.
How It's Given
Method used for this format
Subcutaneous injection, once daily pre-sleep and fasted
Documented in the practitioner reference · Research-practitioner guide
Why this method
Sermorelin is a 29-amino-acid peptide; the subcutaneous route delivers it into circulation without the gastrointestinal degradation that would break the molecule down.
Pre-sleep timing aligns the pharmacologic pulse with the body's own overnight GH release; fasted timing avoids carbohydrate blunting of the same pulse.
Injection sites reported
- Abdomen (rotate sites)
- Front of the thigh
- Avoid scarred, bruised, inflamed, or infected skin
Storage
Before mixing
- Refrigerate 2–8 °C
- Protect from light
- Do not freeze
Documented in the practitioner reference; general RUO practice · Research-practitioner guide
After mixing
- Refrigerate 2–8 °C
- Use within 7–10 days
- Do not freeze
- Discard if cloudy or discoloured
Documented in the practitioner reference · Research-practitioner guide
Handling
- Direct diluent slowly down the vial wall
- Gently swirl until dissolved — do not shake
- New sterile needle each draw
- Do not share vials
General RUO practice · Research-practitioner guide
Storage guidance summarises documented practitioner practice and standard RUO peptide handling. Verify the specific vial's supplied instructions before use.
Common Cycle
The practitioner-reference cadence is a 3-month active cycle followed by a 1-month washout — a duration chosen to prevent pituitary receptor desensitisation.
- Cycle Length
- 3 months on
- Break Before the Next Cycle
- 1-month washout between cycles
- What the Research Shows
- Not defined for grey-market use
Documented in the practitioner reference · Research-practitioner guide
Historical Geref clinical use in pediatric GHD (Thorner 1996) ran continuously across the trial period. That trial context is not the practitioner-reference on/off cadence above.
Compound Overview
Current areas of research
The following are indications and effects for which sermorelin has been studied or was historically approved. There is no currently active approved indication.
- Historically FDA-approved for treatment of pediatric idiopathic growth hormone deficiency (Geref, 1990; NDA withdrawn 2008)
- Diagnostic evaluation of pituitary GH reserve (historical use)
- Adult GH-axis research — improvements in sleep architecture, body composition and IGF-1 have been reported in small studies, but data are limited and off-label
Mechanism of action
Sermorelin is the 29-amino-acid N-terminal fragment of endogenous growth hormone-releasing hormone (GHRH), retaining full biological activity at the pituitary GHRH receptor. It is the shortest sequence that binds and activates the receptor efficiently. Its half-life is very short (~10–20 minutes), which means the GH response is a discrete pulse rather than a sustained elevation.
Historically, sermorelin acetate was FDA-approved as Geref in 1990 for the treatment of pediatric growth hormone deficiency. The NDA was withdrawn from the U.S. market by the sponsor in 2008 for commercial reasons — this was not a safety-related withdrawal. Modern access in the United States is exclusively via compounding pharmacies; there is no currently marketed FDA-approved sermorelin product.
Compared with tesamorelin (the longer, stabilised GHRH(1-44) analogue with documented visceral-fat-reduction pharmacology in the peer-reviewed literature), sermorelin produces a shorter, sharper GH pulse. Its editorial framing on Healthy Mango is research-only.
- The shortest biologically active GHRH sequence — GHRH(1-29) with a C-terminal amide
- Historically FDA-approved as Geref (1990); NDA withdrawn in 2008 for commercial reasons
- Currently accessed exclusively via compounding pharmacies in the U.S.; no active FDA product
Human research
Sermorelin's evidence base rests primarily on the historical pediatric GHD trials (Thorner JCEM 1996), a smaller body of adult GH-axis studies (Walker 1994), and the extensive pharmacological review literature summarising the GHRH(1-29) mechanism (Prakash 1999).
Evidence level is Level B (moderate) — the mechanism is well characterised and the pediatric trials were adequately designed for that historical indication, but the compound does not have a modern, actively approved indication supported by contemporary phase-3 data.
Thorner JCEM 1996
Randomised trial of once-daily sermorelin in growth-hormone-deficient children. Documented growth-velocity acceleration in the first year of therapy. Supported the historical Geref pediatric indication.
Walker JCEM 1994
Randomised, double-blind placebo-controlled trial of GHRH(1-29)NH2 in adults with GH deficiency. Demonstrated GH-axis activation and IGF-1 elevation.
Prakash BioDrugs 1999
Comprehensive review of sermorelin's pharmacology, clinical use in adult-onset GH insufficiency, and comparison with rhGH replacement.
Sermorelin was FDA-approved as Geref in 1990 for pediatric growth hormone deficiency. The NDA was withdrawn by the sponsor in 2008 for commercial reasons; the withdrawal was not related to safety concerns identified in post-marketing surveillance.
There is no currently marketed FDA-approved sermorelin product in the United States. Contemporary access is exclusively via compounding pharmacies under a practitioner's prescription. There is no EMA-authorised sermorelin product for adult or pediatric use.
The mechanism is well established at the receptor level, and the compound's role in the history of GHRH pharmacology is significant. Contemporary use is best understood as off-label / research-only, and the framing of any specific protocol depends on the prescribing clinician.
Safety considerations
The following are drawn from the historical Geref label and published sermorelin trials.
- Injection-site reactions — Erythema, pain, swelling — the most common
- Flushing
- Headache
- Dizziness
- Hyperactivity in pediatric use
- Nausea (uncommon)
- Rare: hypersensitivity
The contraindications below are drawn from the historical Geref labelling. Any decision about suitability should involve a qualified clinician with access to the individual's medical history. There is no currently marketed FDA-approved product; contemporary compounded use is entirely off-label.
- Disruption of the hypothalamic-pituitary axis (hypophysectomy, hypopituitarism, pituitary tumour surgery, head irradiation, head trauma)
- Active malignancy (theoretical risk from IGF-1 elevation)
- Pregnancy
- Known hypersensitivity to sermorelin or excipients
Monitoring
- Baseline and periodic IGF-1 (if used long-term)
- Fasting glucose in participants with diabetes or prediabetes
- Growth response and bone age in pediatric use (historical indication)
- Injection-site reactions across rotation sites
Frequently asked questions
Is sermorelin FDA-approved today?
No. It was FDA-approved as Geref in 1990 for pediatric GH deficiency, but the sponsor withdrew the New Drug Application from the U.S. market in 2008 for commercial reasons. There is no currently marketed FDA-approved sermorelin product. Contemporary access is exclusively via compounding pharmacies.
Was the withdrawal a safety issue?
No. The withdrawal was a commercial decision by the sponsor; it was not driven by post-marketing safety signals. Sermorelin's side-effect profile through the trial and marketed periods was consistent with the GHRH class — mostly injection-site reactions and mild flushing.
How does sermorelin compare to tesamorelin?
Sermorelin is GHRH(1-29) with a very short half-life (~10–20 minutes), producing a discrete GH pulse. Tesamorelin is a longer, stabilised GHRH(1-44) analogue with a somewhat longer half-life (~26–38 minutes) and documented visceral-fat-reduction pharmacology in the peer-reviewed literature. See the Tesamorelin vs Sermorelin comparison for a structured side-by-side.
Why is it used pre-sleep?
The body's endogenous GH pulses primarily during the first hours of sleep. Pre-sleep dosing has been the historical convention because it aligns the pharmacologic signal with the physiologic pulse timing. This is a timing convention rather than a validated head-to-head comparison.
Is sermorelin the same as CJC-1295?
No. CJC-1295 (No DAC) is a modified GHRH(1-29) with N-terminal chemical stabilisation designed to resist enzymatic degradation. It is used only in research contexts and has no approved indication. CJC-1295 DAC is a further modification that binds serum albumin and extends the half-life to approximately 8 days. Both are distinct from sermorelin and from each other.
References
- [1]
Growth hormone-releasing hormone (GHRH)(1-29)NH2 for treatment of GH deficiency in adults: a randomized, double-blind, placebo-controlled trial — Walker RF, Codd EE, Barone FC, et al., Journal of Clinical Endocrinology & Metabolism (1994)
- [2]
Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy — Thorner MO, Rochiccioli P, Colle M, et al., Journal of Clinical Endocrinology & Metabolism (1996)
- [3]
FDA history — GEREF (sermorelin acetate) for injection (approval 1990, withdrawn 2008) — U.S. Food and Drug Administration (2008)
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019863
- [4]
Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? — Prakash A, Goa KL, BioDrugs (1999)
- [5]
Peptides & Compounds — The No-Jargon Guide (v5) — Healthy Mango Editorial, Healthy Mango practitioner reference (2026)
Laboratory Reference Notice
This section summarizes procedures and study parameters reported in published scientific literature and laboratory protocols. It is provided for educational and research reference only and must not be interpreted as medical advice, clinical guidance, or instructions for personal use.
Editorial review pending
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