Sermorelin: the GHRH fragment that was an approved drug

Key points

• Sermorelin is the shortest synthetic peptide, 29 amino acids long, with the full biological activity of GHRH [1].
• FDA approved its two presentations in 1990 and 1997, and in 2013 determined that they were not withdrawn from sale for reasons of safety or effectiveness [2].
• In 110 children with GH deficiency, growth velocity rose from 4.1 to 7.2 cm/year at 12 months, without excessive IGF-1 generation [3].
• In older adults, GHRH(1-29) has been associated with GH and IGF-1 increases toward youthful ranges. The trials are small and short [4][5][6].
• Its plasma half-life is minutes, and with a single nightly injection IGF-1 did not change. The authors concluded it appears less effective than multiple daily doses [5][8].

US status (October 2026): Formerly approved as Geref, withdrawn in 2009 for business reasons that FDA found unrelated to safety or effectiveness, and compoundable as an approved-drug component; MDside’s position is patient-specific, from a licensed 503A pharmacy, with documented pharmaceutical-grade ingredient. See the sermorelin status page.

Sermorelin is the GH-axis peptide with the most complete regulatory history: two approvals, a multicenter pediatric trial and an FDA finding that it left the market for reasons unrelated to safety. Its approved evidence is pediatric. The adult data are small, short and measure hormones more than outcomes.

Sermorelin is the first 29 amino acids of GHRH

Natural growth hormone-releasing hormone (GHRH) has 44 amino acids. Sermorelin corresponds to its first 29, with an amidated end: GHRH(1-29)NH2. It is the shortest synthetic peptide that retains the full biological activity of GHRH, and it specifically stimulates GH secretion from the anterior pituitary [1].

Sermorelin does not supply the hormone from outside, as recombinant GH does. It acts on the GHRH receptor and lets the pituitary release its own GH, which in turn raises IGF-1 [1][4]. That difference in mechanism is at the center of almost all the interest it draws.

• 29: amino acids, the shortest fragment with full GHRH activity [1]
• 4.1 to 7.2 cm/yr: growth velocity in GH-deficient children at 12 months [3]
• 4.3 min: plasma disappearance half-time after intravenous infusion [8]

Two approvals, then a discontinuation

Sermorelin held two US approvals under the GEREF brand. The 0.05 mg presentation (NDA 19-863), approved on December 28, 1990, was indicated for evaluating the pituitary’s ability to secrete GH. The 0.5 and 1.0 mg presentation (NDA 20-443), approved on September 26, 1997, was indicated for treating idiopathic GH deficiency in children with growth failure [2].

In 2008 the holder notified FDA that both presentations were being discontinued, and the agency withdrew the approvals effective June 18, 2009. In 2013, after reviewing its files and the postmarketing adverse-event literature, FDA determined that both products “were not withdrawn from sale for reasons of safety or effectiveness.” That determination allows generic versions to be approved if they meet all other requirements [2]. The document does not detail the commercial reason for the discontinuation.

The same determination is why sermorelin has a compounding route today. The status page explains the conditions, and our guide to 503A vs 503B sourcing covers the pharmacy side.

The pediatric trial supported the approval

The pivotal study is the GEREF International Study Group trial published in 1996: 110 prepubertal children with GH deficiency, previously untreated, received subcutaneous GHRH(1-29) once daily at bedtime for up to one year, in a multicenter open-label study without a control group. 86 were included in the efficacy analysis. Mean growth velocity went from 4.1 cm/year to 8.0 cm/year at 6 months and 7.2 cm/year at 12 months. 74% had a good response at 6 months. Bone age advanced in proportion to height age (ratio 1.04, not significantly different from 1). There was no change in fasting glucose, no excessive IGF-1 generation, and treatment was well tolerated [3].

A 1999 review summarized the profile. Intravenous sermorelin was a rapid and relatively specific diagnostic test, with fewer false positives than other provocative tests. The most frequent adverse effects were transient facial flushing and injection-site pain. The same review noted that the recommended dose had not been compared directly with somatropin. With other schedules (continuous infusion or three daily doses), growth-velocity gains were smaller than with daily somatropin, and the effect on final adult height had not been determined [1].

Older-adult studies are small and short

At the US National Institute on Aging, 10 men aged about 68 received GHRH(1-29) twice daily for 14 days. At the high dose, 24-hour GH and IGF-1 rose until they no longer differed from those of 9 young men, with no change in fasting glucose, blood pressure or laboratory tests [4].

With a single nightly injection for 6 weeks, in 11 men aged 64 to 76, nocturnal GH rose and IGF-1 did not change. 2 of 6 strength measures improved, with no change in DEXA body composition. The authors concluded that “single nightly doses of GHRH are less effective than multiple daily doses” [5]. In 19 men and women aged 55 to 71, in a single-blind trial with a 4-week placebo lead-in, 16 weeks of an analog, [Nle27]GHRH(1-29)NH2, raised GH and IGF-1, and lean mass and insulin sensitivity increased in men only. IGF-1 returned toward baseline by 16 weeks [6]. In 89 healthy adults aged about 68, 6 months of daily GHRH were associated with better performance on several cognitive tests versus placebo [7].

The case for sermorelin rests on pulsatility

The reason sermorelin stays in the conversation is physiological. According to the National Institute on Aging authors, in GH-deficient children and young adults GHRH raises GH and IGF-1 “while preserving physiological GH release” [4]. In treated children there was no excessive IGF-1 generation [3]. The response remains subject to the axis’s own regulation, something exogenous GH lacks.

The contrast with recombinant GH in healthy older adults is instructive. A systematic review of 18 study populations found 2.1 kg less fat and 2.1 kg more lean mass, with no weight change, along with more edema, arthralgias, carpal tunnel syndrome and gynecomastia, and somewhat more diabetes and impaired fasting glucose. It concluded that “GH cannot be recommended as an antiaging therapy” [10]. In a 26-week trial in 131 adults aged 65 to 88, diabetes or glucose intolerance occurred in 18 GH-treated men versus 7 not receiving GH [11]. These data are for exogenous GH. No trial has directly compared its safety with that of sermorelin in adults.

A half-life of minutes is both advantage and limit

GHRH(1-29)NH2 is cleared in minutes. In an intravenous infusion in 10 healthy men, its disappearance half-time was 4.3 minutes [8]. Even so, after an intravenous injection GH stayed elevated for about 3 hours [9]. That profile produces brief GH pulses, consistent with physiology, and it explains why a single nightly dose had limited effects on IGF-1 [5].

Industry answered with more stable analogs. Tesamorelin, a GHRH analog with a current US approval for excess abdominal fat in HIV with lipodystrophy [13], has phase 3 trials reviewed in Tesamorelin: the GHRH analog that did clear FDA. Long-acting secretagogues and ghrelin agonists are reviewed in CJC-1295, ipamorelin and MK-677: the GH and IGF-1 debate.

Where the evidence ends

• The approved efficacy evidence is pediatric. The registered indications were diagnosis of somatotroph function and idiopathic GH deficiency in children [2]. The effect on final adult height had not been determined [1].
• The older-adult studies are small and short. They enrolled 10 to 89 participants, for 2 weeks to 6 months, with intermediate measures such as GH, IGF-1 or cognitive tests in place of hard clinical outcomes [4][5][6][7].
• Not all used the same molecule. One of the most cited adult studies used an analog, [Nle27]GHRH(1-29)NH2, and the abstract of the cognitive trial does not specify the GHRH form used [6][7].
• Results vary with schedule and sex. A single nightly dose did not raise IGF-1 [5], and changes in lean mass and insulin sensitivity appeared only in men [6].
• Today’s product is not the original GEREF. A 2026 review points to uncertainty about the composition and dose of GH-axis peptides in unregulated supply chains [12].

What this means for you

Sermorelin has a regulatory foundation most GH-axis peptides lack [2][3], and a mechanism that preserves the axis’s physiological regulation [4]. Its adult evidence is thin, so set expectations on hormone levels and say plainly that hard outcomes are unstudied. Source it only from a licensed pharmacy with documented ingredient, never from research-use-only supply. If you are adding it to a hormone therapy program, put the dosing schedule question into your protocol, because a single nightly dose underperformed [5].

References

1. 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):139-57. PMID 18031173. Link
2. U.S. Food and Drug Administration. Determination That GEREF (Sermorelin Acetate) Injection, 0.5 Milligrams Base/Vial and 1.0 Milligrams Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 Milligrams Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness. Federal Register. 2013;78(42):14095-14096. Link
3. Thorner 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):1189-96. PMID 8772599. Link
4. Corpas E, et al. 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):530-5. PMID 1379256. Link
5. Vittone 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. PMID 9005976. Link
6. Khorram O, et al. 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):1472-9. PMID 9141536. Link
7. Vitiello MV, et al. Growth hormone releasing hormone improves the cognition of healthy older adults. Neurobiol Aging. 2006;27(2):318-23. PMID 16399214. Link
8. Soule S, et al. Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. J Clin Endocrinol Metab. 1994;79(4):1208-11. PMID 7962295. Link
9. Wilton P, et al. Pharmacokinetics of growth hormone-releasing hormone(1-29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration. Acta Paediatr Suppl. 1993;388:10-5. PMID 8329825. Link
10. Liu H, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med. 2007;146(2):104-15. PMID 17227934. Link
11. Blackman MR, et al. Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. JAMA. 2002;288(18):2282-92. PMID 12425705. Link
12. Dominikowski A, et al. The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration. Front Endocrinol (Lausanne). 2026;17:1822475. PMID 42395176. Link
13. Theratechnologies Inc. EGRIFTA WR (tesamorelin) prescribing information. DailyMed, U.S. National Library of Medicine. Revised 3/2025. Link

This is general information, not medical or legal advice. Rules vary by state and change. Confirm your own facts with counsel.