Prompting the pituitary to make its own growth hormone
Injection · 503A Compounding
Educational content. This page describes Sermorelin for informational purposes only and is not medical advice, diagnosis, or treatment. Consult a licensed provider before starting, stopping, or modifying any therapy.
Researched and maintained by the PepHookup team. Regulatory status last verified April 12, 2026.
Nightly GHRH(1-29) for 16 weeks increased lean body mass in men and skin thickness in both sexes, with improved insulin sensitivity in men.[3]
In one small aging cohort, the sermorelin analog raised circulating B cells by roughly 30% and IL-2 receptor-expressing lymphocytes by about 70%, an early and preliminary finding.[4]
A 20-week controlled trial of a related GHRH analog improved executive function in older adults with and without mild cognitive impairment, suggesting a class effect worth following.[6]
Sermorelin is a synthetic 29-amino-acid peptide, GHRH(1-29)NH2, that reproduces the first 29 residues of human growth hormone-releasing hormone. That fragment is the shortest portion of the native 44-residue hormone that retains full ability to stimulate the pituitary, which is why it became the basis for a pharmaceutical product.
It was approved by the FDA as Geref (sermorelin acetate, NDA 020443) for diagnosing and treating growth hormone deficiency in children with growth failure. The manufacturer discontinued Geref in 2008, and an FDA Federal Register determination later confirmed the withdrawal was a commercial decision, not a finding about safety or effectiveness.
Today sermorelin is used off-label in adults to address the gradual decline in growth hormone that accompanies aging. Because it stimulates the pituitary instead of supplying growth hormone directly, the hormone it produces is still released in natural pulses and remains subject to the body's own feedback braking.
Sermorelin binds GHRH receptors on the somatotroph cells of the anterior pituitary. This triggers synthesis and release of growth hormone, which in turn drives the liver to produce IGF-1, the mediator behind most of growth hormone's downstream tissue and metabolic effects.
The release stays self-limiting because the opposing hormone somatostatin continues to brake the pituitary. That feedback keeps growth hormone within a physiologic range and is the main reason a secretagogue like sermorelin is generally considered gentler than injecting recombinant growth hormone, which bypasses these controls entirely.
Sermorelin clears quickly, with a plasma half-life on the order of 10 to 20 minutes, so it acts as a short pulse rather than a sustained signal. Dosing is typically timed for bedtime because endogenous GHRH normally drives the large overnight growth hormone surge, a dependence demonstrated when blocking GHRH receptors nearly abolished nocturnal GH secretion.
Prompting the pituitary to make its own growth hormone
Sermorelin is GHRH(1-29)NH2, the active fragment of growth hormone-releasing hormone. It binds GHRH receptors on pituitary somatotrophs to stimulate pulsatile growth hormone release, which raises hepatic IGF-1. Because somatostatin feedback stays intact and the peptide clears within minutes, GH remains within a physiologic range rather than being driven to supraphysiologic levels as it can be with direct growth hormone injection.
Twice-daily GHRH(1-29) produced dose-related increases in 24-hour GH and IGF-1 in older men. At the high dose, GH and IGF-1 measures were no longer significantly different from those of the young men.
Corpas E, Harman SM, Pineyro MA, Roberson R, Blackman MR · J Clin Endocrinol Metab, 75(2):530-535 (1992) · PubMed
Nightly [Nle27]GHRH(1-29)NH2 at 10 mcg/kg raised IGF-1 within 2 weeks, increased lean body mass in men, increased skin thickness in both sexes, and improved insulin sensitivity, well-being, and libido in men.
Khorram O, Laughlin GA, Yen SS · J Clin Endocrinol Metab, 82(5):1472-1479 (1997) · PubMed
By 16 weeks the GHRH analog increased circulating B cells by about 30%, mitogen responsiveness by about 50%, and IL-2 receptor-expressing lymphocytes by about 70%, with no adverse effects. The cohort was small and the findings are preliminary.
Khorram O, Yeung M, Vu L, Yen SS · J Clin Endocrinol Metab, 82(11):3590-3596 (1997) · PubMed
Once-daily subcutaneous sermorelin nearly doubled mean height velocity from about 4 to 8 cm per year, with roughly three-quarters of children classified as good responders and no adverse biochemical or hormonal changes over 12 months.
Thorner M, Rochiccioli P, Colle M, et al. · J Clin Endocrinol Metab, 81(3):1189-1196 (1996) · PubMed
A related GHRH analog (tesamorelin, 1 mg/day) improved executive function with a trend toward better verbal memory, raised IGF-1 by 117% within the physiologic range, and reduced body fat by 7.4%. This used a different GHRH analog, so it is supportive class evidence rather than direct sermorelin data.
Baker LD, Barsness SM, Borson S, et al. · Arch Neurol, 69(11):1420-1429 (2012) · PubMed
start low, go slow
Subcutaneous (adults, off-label)
Subcutaneous (pediatric GH deficiency, original FDA label)
Subcutaneous (adults, off-label): There is no FDA-approved adult dose. The figures shown reflect common compounded-prescribing patterns.
Subcutaneous (pediatric GH deficiency, original FDA label): This was the dosing on the original Geref label for diagnosing and treating childhood GH deficiency, included for context.
Dosing, cycle length, and monitoring are determined by a licensed provider based on your goals, baseline labs, and response.
Bedtime administration is preferred because the largest natural growth hormone pulse occurs overnight, and endogenous GHRH is what drives that surge.
Because sermorelin works by stimulation rather than replacement, effects build gradually. Periodic IGF-1 measurement is commonly used to confirm the pituitary is responding and to guide adjustments.
Sermorelin carries one of the better-characterized safety records among growth hormone peptides, owing to its FDA approval history and multicenter pediatric trials. No adverse biochemical or hormonal changes were reported over 12 months in the 110-child Geref International study.
Because somatostatin feedback and rapid clearance keep growth hormone within a physiologic range, sermorelin avoids the supraphysiologic exposure that drives many of the side effects seen with direct recombinant GH.
Most adverse events are local and transient, chiefly injection site reactions and flushing. Long-term outcome data in healthy aging adults remain limited, and adult use is off-label.
| Peptide | Primary Use | Administration | Cycle Length | Key Differentiator |
|---|---|---|---|---|
| Sermorelin | GH restoration and healthy aging | Subcutaneous injection, daily at bedtime | 3-6 months | The GHRH analog with prior FDA approval and a multi-decade clinical record, preserving natural feedback rather than replacing growth hormone |
| SS-31 (Elamipretide) | Mitochondrial restoration and rare mitochondrial disease | Subcutaneous injection (daily); IV in trials | Ongoing daily dosing | The first FDA-approved mitochondria-targeted therapeutic; binds cardiolipin on the inner mitochondrial membrane to support electron transport efficiency |
| Tesamorelin | Visceral Fat & GHRH Signaling | Subcutaneous Injection | Ongoing daily | The only FDA-approved GHRH analog, with Phase III data in over 800 patients, documented liver-fat reduction, and physiologic pulsatile GH release |
| GHK-Cu | Anti-Aging & Skin Regeneration | Topical, Injection | 8-12 weeks | A naturally occurring copper-carrier peptide that rebuilds the skin matrix and, per gene-expression analysis, shifts expression of about a third of human genes toward repair |
| Glutathione | Antioxidant & Detoxification | IV, Oral, Sublingual, Topical | Ongoing supplementation | The body's own master antioxidant, with controlled human data showing oral and sublingual forms can raise body stores and immune markers |
This substance is in Category 1 of the FDA's 503A bulk drug substances evaluation. Licensed 503A pharmacies may compound it under FDA enforcement discretion while the agency continues its review.
Previously FDA-approved as Geref (NDA 020443) for pediatric growth hormone deficiency. Discontinued by the manufacturer in 2008 for commercial reasons, not safety concerns. Compoundable under the 'component of FDA-approved drug' pathway: because sermorelin was previously an approved drug, 503A pharmacies may compound it without it appearing on the interim Category 1 list.
Manufacturer discontinued Geref (sermorelin acetate, NDA 020443) for commercial reasons
Last verified April 12, 2026. PepHookup tracks public FDA actions. This is not legal or medical advice.
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