Sermorelin

Overview

Sermorelin is a synthetic analog of growth hormone-releasing hormone (GHRH) consisting of the first 29 amino acids of the 44-aa native hormone — the shortest fragment that retains full biological activity. It was FDA-approved in the 1990s as Geref (EMD Serono) for diagnostic testing of pituitary GH reserve and later for pediatric idiopathic GH deficiency, but was withdrawn from the US market in 2008–2009 at the manufacturer's request for commercial reasons (not safety or efficacy). It remains on the FDA Category 1 list of bulk substances nominated for use in 503A compounding, where it is now widely prescribed off-label for adult GH insufficiency and "anti-aging" indications.

Mechanism of Action

Sermorelin binds GHRH receptors on anterior pituitary somatotrophs, activating Gs-adenylyl cyclase-cAMP-PKA signaling to stimulate both GH gene transcription and pulsatile GH vesicle release. Because GH release remains subject to somatostatin feedback, sermorelin preserves physiologic pulsatility and avoids the continuous supraphysiologic exposure seen with exogenous recombinant GH. Plasma half-life is short (~11–12 min), which is why bedtime subcutaneous dosing is used to augment the natural nocturnal GH pulse.

Research Summary

Geref received FDA approval in the 1990s based on pediatric GHD trials and was used for the GHRH stimulation test of pituitary function. Vittone et al. (1997) showed nightly sermorelin in healthy elderly men raised IGF-1 and modestly increased lean mass. Khorram, Laughlin & Yen (1997) demonstrated that 16 weeks of nightly GHRH(1-29) in adults aged 55–71 restored GH/IGF-1 toward young-adult levels with small gains in lean mass and skin thickness. Walker (2006) reviewed sermorelin's rationale as a more physiologic alternative to rhGH in adult-onset GH insufficiency. EMD Serono discontinued Geref in 2008; FDA withdrew approval of NDAs 19-863 and 20-443 in 2009 and later (2013) affirmed the withdrawal was not for reasons of safety or effectiveness.

Dosing Information

Reported Side Effects

• Injection site reactions — redness, pain, or swelling (most common; ~16% in Geref trials)
• Facial flushing
• Headache
• Nausea
• Dizziness
• Transient dysgeusia (altered taste)

Research References

• Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? (Walker, Clin Interv Aging) (2006)
• Endocrine and metabolic effects of long-term administration of [Nle27]GHRH-(1-29)-NH2 in age-advanced men and women (Khorram, Laughlin & Yen, J Clin Endocrinol Metab) (1997)
• Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men (Vittone et al., Metabolism) (1997)
• Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic GH deficiency (Prakash & Goa, BioDrugs) (1999)
• FDA Federal Register: Determination That GEREF (Sermorelin Acetate) Injection Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness (2013)