Sermorelin

How does Sermorelin work?

Sermorelin reproduces the first 29 amino acids of human GHRH with an amidated C-terminus, GHRH(1-29)-NH2, the shortest synthetic peptide that retains the hormone's full biological activity1. Its residue sequence, from PubChem, is shown in Figure 1.

Because it acts upstream of the pituitary, sermorelin's effect depends on the gland's capacity to respond. A review notes that a normal GH response to intravenous sermorelin cannot exclude GH deficiency caused by a hypothalamic problem1.

How long does Sermorelin last in the body?

In 30 healthy men, the lowest intravenous dose tested (0.25 µg/kg) produced significant GH release, with maximal peaks at 1–2 µg/kg. The peptide was rapidly eliminated, yet GH levels stayed elevated for about three hours. Nasal absorption was poor, with bioavailability of only 3–5%: roughly 50 µg/kg intranasally matched 1 µg/kg intravenously5.

What did the clinical trials find?

Treatment of GH deficiency in children. A 1987 Lancet report treated 18 prepubertal GH-deficient children with twice-daily subcutaneous GHRH(1-29)-NH2. Height velocity rose in 12, and 8 gained more than 2 cm/year over their pre-treatment rate (range 2.7–11.2 cm/year), sustained over 6–18 months. Four children who had previously received human GH grew more slowly on GHRH. The authors called it an alternative to GH for some children, with ideal dosing still to be established4.

Head-to-head with growth hormone. A 1993 study randomized 60 children with GH deficiency of hypothalamic origin to GHRH(1-29)-NH2 at 30 or 60 µg/kg/day or to GH. After six months, height velocity was 9.2, 9.3 and 14.6 cm/year respectively — GH was significantly better. IGF-1 rose and then fell back to pre-treatment levels during GHRH infusion, and the authors concluded this approach was unlikely to be as effective as GH3.

The overall pediatric picture. A 1999 review concluded that once-daily subcutaneous sermorelin given at bedtime was effective in treating some prepubertal children with idiopathic GH deficiency, with sustained increases in height velocity over 12 months and limited data to 36 months, but that its effect on final adult height had not been determined1.

Adults. Interest in adult use — often framed as anti-aging — is far larger than the evidence. A 2006 review discussed sermorelin as an approach to adult-onset GH insufficiency66PubMedSermorelin: a better approach to management of adult-onset growth hormone insufficiency?. Walker RF Clin Interv Aging. 2006.. The PubMed record contains many physiology studies that use GHRH(1-29) as a test agent77PubMedPubMed search: (sermorelin[tiab] OR "GHRH(1-29)"[tiab] OR "GRF(1-29)"[tiab]). 366 records at fetch., but these do not establish long-term benefit.

What adverse events were reported in studies?

Single intravenous doses and repeated subcutaneous doses were well tolerated in pediatric studies; transient facial flushing and injection-site pain were the most frequent events1. Antibodies against GHRH were common: they developed in 14 of 18 children in the 1987 study4 and in 39 of 40 on continuous infusion in 1993, where they had nearly disappeared nine months after stopping and did not correlate with growth3.