Research in plain language
Sermorelin
What it is
Sermorelin (also called GHRH(1-29), GRF(1-29)NH2, or Geref) is a synthetic 29-amino-acid peptide copying the first 29 residues of human growth-hormone-releasing hormone, the shortest fragment that still fully stimulates the pituitary. It binds GHRH receptors on pituitary somatotrophs and triggers the body's own pulsatile growth-hormone (GH) release. It was historically studied and FDA-approved as a diagnostic agent to test pituitary GH reserve and as a treatment to accelerate growth in children with GH deficiency; smaller studies also tested it in idiopathic short stature, in older adults, and by the intranasal route.
How studies used it
- Model
- Human, prepubertal children with GH deficiency (n=110 enrolled, 86 evaluable)
- Studied for
- Growth hormone deficiency (treatment to accelerate linear growth)
- Dose
- 0.030 mg/kg/day (30 micrograms/kg/day, already per-kg as published)
- Dosing
- once daily at bedtime
- Route
- subcutaneous
- Duration
- 12 months
Effects measured: Mean height velocity rose from 4.1 +/- 0.9 cm/yr at baseline to 8.0 +/- 1.5 cm/yr at 6 months and 7.2 +/- 1.3 cm/yr at 12 months. 74% of children were classed as good responders at 6 months. Bone-age progression stayed proportional to height age (ratio 1.04 +/- 0.58 at 12 months), with no excessive IGF-I generation.
Side effects: No adverse changes in biochemical or hormonal panels, no change in fasting glucose; described as well tolerated overall (injection-site reactions not detailed in the abstract).
- Model
- Human, prepubertal children with idiopathic short stature (n=18; ages 4.3-11.0 yr; 17 male, 1 female)
- Studied for
- Idiopathic short stature (height below 3rd percentile, peak GH >20 mU/L, i.e. not classically GH-deficient)
- Dose
- 0.020 mg/kg per dose (20 micrograms/kg, per-kg as published), so 0.040 mg/kg/day total
- Dosing
- twice daily
- Route
- subcutaneous
- Duration
- 12 months treatment plus 12 months post-treatment follow-up
Effects measured: Mean height velocity increased from 4.8 cm/yr before treatment to 7.2 cm/yr at 12 months (P=0.001); mean predicted final height rose by 3.4 cm. Slower-growing children responded more. After stopping, growth velocity fell back ('catch-down') to pretreatment levels within 6-12 months.
Side effects: Fasting blood glucose and insulin rose during therapy. No injection-site reactions specified in the abstract.
- Model
- Human, prepubertal children with hypothalamic-origin GH deficiency (n=43; ages 4.3-18.9 yr, mean 10.4 yr)
- Studied for
- Growth hormone deficiency: head-to-head growth comparison of GHRH(1-29)-NH2 versus growth hormone (GH)
- Dose
- Low-dose GHRH 0.030 mg/kg/day (30 micrograms/kg/day, n=15); high-dose GHRH 0.060 mg/kg/day (60 micrograms/kg/day, n=12). Comparator: GH 0.1 IU/kg/day (n=16). Doses per-kg as published.
- Dosing
- GHRH given as three daily subcutaneous injections; GH given once daily
- Route
- subcutaneous
- Duration
- 6 months
Effects measured: Height velocity increased by 2 cm/yr or more in all but 2 children. Velocity was lowest in the low-dose GHRH group; high-dose GHRH was comparable to GH. An increase in height SDS for bone age occurred only in the GH-treated group, i.e. GH gave a measurable edge on this index. Low-dose GHRH showed a priming effect on later GH responses, while GH treatment blunted later GHRH-stimulated GH.
Side effects: No adverse events reported in this study (abstract did not detail side effects).
- Model
- Human, children/adolescents evaluated for short stature (n=131: 45 with idiopathic GHD, 86 without; plus 11 young-adult volunteers)
- Studied for
- Diagnostic GH-stimulation test for suspected GH deficiency (not treatment)
- Dose
- 0.001 mg/kg (1 microgram/kg, per-kg as published), single dose
- Dosing
- single bolus
- Route
- intravenous
- Duration
- single test, GH sampled over 120 minutes
Effects measured: Using a peak GH cut-off of >10 ng/mL: 3 of 86 non-GHD children fell below the cut-off (false 'deficient'), and 11 of 45 known GHD children exceeded it (false 'normal'), showing meaningful overlap and imperfect test discrimination. In GHD patients peak GH fell with increasing age, and GRF-stimulated GH correlated with nocturnal GH peaks. Authors concluded GRF testing plus a basal somatomedin-C (IGF-I) level is a safe, convenient screen but that additional tests are sometimes needed.
Side effects: No adverse events reported in this study.
- Model
- Human, short prepubertal children with GH deficiency (n=8)
- Studied for
- GH deficiency: pilot test of the intranasal route (NEGATIVE/null overall result)
- Dose
- 0.050 mg/kg per dose (50 micrograms/kg, per-kg as published), three times daily
- Dosing
- three times daily
- Route
- intranasal
- Duration
- 6 months
Effects measured: On day 1 peak GH ranged 10-85 mIU/L after dosing, but peak amplitudes were variably reduced by 6 weeks and 6 months. Knemometric (short-term) growth rate rose from 0.24 to 0.48 mm/week at 6 weeks (P=0.03) but then fell rapidly; mean 6-month stadiometric height velocity showed NO increase. Anti-GHRH antibodies appeared in 3 of 8 patients. Authors concluded intranasal GHRH in this form is not suitable for children.
Side effects: Local tolerance good in only 1 patient; most reported sneezing right after insufflation, rhinorrhoea and mild mucosal burning. Treatment was discontinued in 2 patients.
- Model
- Human, healthy nonobese older men (n=10; mean age 68.0 yr) vs healthy young men (n=9; mean 26.2 yr) as reference
- Studied for
- Age-related decline in GH and IGF-I (whether GHRH can reverse it)
- Dose
- Absolute doses: low 0.5 mg and high 1.0 mg per injection. Mean body weight was NOT reported in the abstract, so a per-kg figure cannot be calculated without inventing a weight; doses are given as absolute amounts for nonobese older men.
- Dosing
- twice daily; the two dose levels given in separate 14-day blocks split by a 14-day washout
- Route
- subcutaneous
- Duration
- 14 days per dose level
Effects measured: High-dose GHRH significantly raised mean 24-hour GH (P<0.001) and IGF-I (P<0.005) in older men; after high-dose treatment there were no significant GH/IGF-I differences between the older and young men, i.e. the age-related fall was reversed over this short period.
Side effects: GHRH did not affect fasting glucose, urinary C-peptide, blood pressure, or chemistry/hematology profiles. Serum phosphate increased during treatment (P<0.05).
How solid the evidence is
Evidence is entirely HUMAN, which is a strength, but it is old (1986-1996) and methodologically modest by current standards. Most treatment trials are small, open-label or single-group with no placebo arm (PMID 8772599 n=86 evaluable, open-label; PMID 7955460 n=18 open-label; PMID 8329828 n=8 pilot). The strongest comparative signal (PMID 8329826, n=43) is a randomized comparison that actually favored growth hormone over GHRH on the bone-age height-SDS index, so GHRH was at best comparable to GH only at the higher 60 microg/kg dose. The intranasal study (PMID 8329828) is essentially a NEGATIVE trial: no 6-month height-velocity gain, antibody formation in 3 of 8, and the authors rejected that route. The idiopathic-short-stature trial (PMID 7955460) showed catch-down growth after stopping and rising glucose/insulin, tempering its benefit. The diagnostic test (PMID 2880720) has documented false-positive and false-negative overlap, so a single GRF test does not by itself diagnose GHD. The adult/aging data (PMID 1379256) are a 14-day physiology study showing only that GH/IGF-I can be raised short-term, NOT clinical endpoints like strength or function; that study used absolute mg doses with no reported body weight, so its per-kg dose cannot be honestly derived. Across studies sermorelin was generally well tolerated, with the main reported issues being rising glucose/insulin on chronic dosing, increased phosphate, anti-GHRH antibody formation (notably intranasal), and route-specific local effects (intranasal sneezing/rhinorrhoea/burning). Subcutaneous injection-site and flushing reactions are commonly cited for this class but were not quantified in these particular abstracts. None of these are modern, adequately powered, placebo-controlled efficacy trials.
Sources
- 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(PMID 8772599)
- Kirk JM, Trainer PJ, Majrowski WH, Murphy J, Savage MO, Besser GM. Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity. Clin Endocrinol (Oxf). 1994(PMID 7955460)
- Neyzi O, Yordam N, Ocal G, et al. Growth response to growth hormone-releasing hormone(1-29)-NH2 compared with growth hormone. Acta Paediatr Suppl. 1993(PMID 8329826)
- Ranke MB, Gruhler M, Rosskamp R, Brugmann G, Attanasio A, Blum WF, Bierich JR. Testing with growth hormone-releasing factor (GRF(1-29)NH2) and somatomedin C measurements for the evaluation of growth hormone deficiency. Eur J Pediatr. 1986(PMID 2880720)
- Hummelink R, Sippell WG, Benoit KG, Danielson K, Faijerson Y. Intranasal administration of growth hormone-releasing hormone(1-29)-NH2 in children with growth hormone deficiency: effects on growth hormone secretion and growth. Acta Paediatr Suppl. 1993(PMID 8329828)
- Corpas E, Harman SM, Pineyro MA, Roberson R, Blackman MR. 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(PMID 1379256)
- Chen RG, et al. (companion GHRH vs GH growth analyses, Acta Paediatr Suppl 1993) - related comparative pediatric data(PMID 8329830)
Study data, research use only. No established human dosing protocol.