Key papers ✓ 2✗ 2~ 3? 1

• ✗ Negative human RCTActa Paediatr Suppl · 1993

  A comparative study of growth hormone (GH) and GH-releasing hormone(1-29)-NH2 for stimulation of growth in children with GH deficiency.

  Humans60 peopleRandomized6 months

  Randomized comparison of GHRH(1-29)-NH2 (30 or 60 ug/kg/day) vs GH (0.1 IU/kg/day)

  In 60 GH-deficient children randomized for 6 months, GHRH(1-29)-NH2 gave height velocities of ~9.2-9.3 cm/year vs 14.6 cm/year with GH (p < 0.01); nearly all GHRH-treated children developed GHRH antibodies.

  Key resultMean height velocities at 6 months were 9.2, 9.3 and 14.6 cm/year (low-dose GHRH, high-dose GHRH, GH); growth better with GH (p < 0.01); all 20 high-dose and 19 of 20 low-dose GHRH patients developed GHRH antibodies

  Study details

  Studied

  Children with proven growth hormone deficiency of hypothalamic origin

  Compared with

  Growth hormone

  Main outcome

  Height velocity

  Sample

  60 GH-deficient children randomized into three equal groups of 20

  Authors' conclusion

  Continuous GHRH(1-29)-NH2 infusion over 6 months, or a depot preparation, is unlikely to be as effective as GH for promoting growth in GHD.

  Limitations

  Continuous infusion regimen over 6 months; GHRH antibodies developed in nearly all treated children.

  DOI 10.1111/j.1651-2227.1993.tb12834.xPubMed 8329830
• ~ Mixed human RCTActa Paediatr Suppl · 1993

  Growth response to growth hormone-releasing hormone(1-29)-NH2 compared with growth hormone.

  Humans43 peopleRandomized6 months

  Randomized three-arm comparison: low-dose GHRH(1-29)-NH2 (30 ug/kg/day), high-dose (60 ug/kg/day), or GH (0.1 IU/kg/day)

  In 43 children with hypothalamic GH deficiency, high-dose GHRH(1-29)-NH2 for 6 months gave height velocity comparable to GH, but only GH improved height SDS for bone age; the low dose was least effective.

  Key resultHeight velocity lowest in the low-dose group but comparable in high-dose and GH groups; height SDS for bone age increased only in the GH group

  Study details

  Studied

  Prepubertal children aged 4.3-18.9 years with GH deficiency of hypothalamic origin

  Compared with

  Growth hormone

  Main outcome

  Height velocity, height SDS for bone age, GH and IGF-I responses

  Sample

  43 prepubertal children (low-dose n=15, high-dose n=12, GH n=16)

  Authors' conclusion

  High-dose GHRH(1-29)-NH2 gave height velocity comparable to GH, but only GH increased height SDS for bone age.

  Limitations

  Abstract truncated in source; small groups.

  DOI 10.1111/j.1651-2227.1993.tb12828.xPubMed 8329826
• ✓ Positive human trialJ Clin Endocrinol Metab · 1996

  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.

  Humans110 peopleOpen-labelUp to 1 year

  Multicenter open-label study, 30 ug/kg GHRH-(1-29) subcutaneously at bedtime

  In an open-label multicenter study of 110 GH-deficient children, nightly sermorelin raised height velocity from 4.1 to 7.2 cm/year at 12 months without adverse biochemical changes.

  Key resultMean height velocity rose from 4.1 +/- 0.9 cm/yr at baseline to 8.0 +/- 1.5 (6 months) and 7.2 +/- 1.3 cm/yr (12 months); 74% were good responders at 6 months

  Study details

  Studied

  Prepubertal GH-deficient children

  Compared with

  None (open-label, baseline comparison)

  Main outcome

  Height velocity, bone age progression, safety

  Sample

  110 previously untreated prepubertal GH-deficient children, 86 eligible for efficacy analysis

  Authors' conclusion

  Once-daily subcutaneous 30 ug/kg GHRH-(1-29) was effective in increasing height velocity in GH-deficient children and was well tolerated.

  Limitations

  Open-label, no control group; one year.

  DOI 10.1210/jcem.81.3.8772599PubMed 8772599
• ~ Mixed human trialJ Clin Endocrinol Metab · 1997

  Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women.

  HumansTen women and 9 men aged 55-71Placebo-controlled5 months (16 weeks active treatment)

  Single-blind placebo-controlled trial: 4 weeks saline then 16 weeks of [Nle27]GHRH-(1-29)-NH2 10 microg/kg nightly

  In 19 adults aged 55-71 (single-blind, placebo run-in), 16 weeks of a closely related GHRH(1-29) analog raised GH and IGF-I and skin thickness; lean mass, insulin sensitivity and well-being improved in men only; transient hyperlipidemia occurred.

  Key result12-h integrated nocturnal GH increased in women (P < 0.01) and men (P < 0.05); IGF-I increased (P < 0.05); lean body mass increased in men only (P < 0.05)

  Study details

  Studied

  Age-advanced men and women aged 55-71

  Compared with

  Placebo run-in (same subjects)

  Main outcome

  GH, IGF-I, body composition, insulin sensitivity, quality of life

  Authors' conclusion

  Nightly GHRH analog activated the somatotropic axis; lean mass, insulin sensitivity, well-being and libido improved in men but not women, and skin thickness increased in both. The only adverse effect was transient hyperlipidemia.

  Limitations

  Single-blind, small sample; tested a GHRH analog ([Nle27]GHRH-(1-29)-NH2), not sermorelin itself.

  DOI 10.1210/jcem.82.5.3943PubMed 9141536
• ✓ Positive reviewBioDrugs · 1999

  Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency.

  No new data

  Drug review

  Review concluding sermorelin is a useful diagnostic test and effective in some GH-deficient children, though height gains were smaller than with somatropin and effects on final height were unknown; generally well tolerated.

  Study details

  Studied

  Children with idiopathic growth hormone deficiency

  Authors' conclusion

  Sermorelin 1 microg/kg IV is a useful diagnostic test for GH deficiency, and limited data suggest once-daily subcutaneous 30 microg/kg is effective in some prepubertal children; effect on final adult height is yet to be determined.

  Limitations

  Limited data; not directly compared with somatropin, which gave larger height velocity increases.

  DOI 10.2165/00063030-199912020-00007PubMed 18031173
• ? Inconclusive reviewSports Med · 2026

  Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance.

  No new data

  Narrative review of approved and unapproved peptides including sermorelin

  Narrative review including sermorelin among peptides marketed for injury recovery and performance; notes rigorous human safety data are scarce for these uses.

  Study details

  Authors' conclusion

  Many unapproved peptides show favorable tissue repair and metabolic outcomes in animal models, but rigorous human safety data are scarce and there is potential for serious harm to patients.

  Limitations

  Covers twelve peptides, not sermorelin alone; no original data.

  DOI 10.1007/s40279-026-02437-0PubMed 41966639
• ~ Mixed human trialMetabolism · 1997

  Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men.

  Humanssize not reportedNo control group6 weeks

  Open before-and-after treatment study with nightly self-injection; no control group described

  In 11 healthy men aged 64-76 with low IGF-I, 6 weeks of nightly GHRH 1-29 injections raised nocturnal GH release and improved 3 of the muscle strength or endurance tests but did not change IGF-I, body composition or muscle histology; no significant adverse effects were seen.

  Key resultNocturnal GH release rose (P < .02) with no change in IGF-I; upright row (P < .02), shoulder press (P < .04) and abdominal crunch (P < .03) improved; DEXA muscle and fat did not change

  Study details

  Studied

  Healthy, ambulatory, non-obese men aged 64 to 76 years with low baseline IGF-I

  Compared with

  Before-treatment baseline

  Main outcome

  GH secretion, IGF-I, muscle strength and energy metabolism, body composition

  Sample

  Eleven healthy elderly men (spelled out in the abstract)

  Authors' conclusion

  Single nightly GHRH 1-29 doses increased GH secretion and improved some measures of muscle strength and endurance without sustained IGF-I or body composition changes, and without significant adverse effects.

  Limitations

  n = 11, no placebo group stated, many outcomes tested.

  DOI 10.1016/s0026-0495(97)90174-8PubMed 9005976
• ✗ Negative human trialActa Paediatr Suppl · 1993

  Growth hormone (GH) profiles in response to continuous subcutaneous infusion of GH-releasing hormone(1-29)-NH2 in children with GH deficiency.

  Humans6 peopleNo control group6 months

  Open, uncontrolled continuous subcutaneous infusion study

  In 6 children with partial GH deficiency given continuous subcutaneous GHRH(1-29)-NH2 for 6 months, GH output rose early then fell back by 3 to 6 months (one child had GH fully suppressed) and only 3 grew significantly.

  Key result24-hour integrated GH rose from 1.6 to 3.5 micrograms/l/minute early, then fell to 1.9 by 6 months

  Study details

  Studied

  Children with partial growth hormone deficiency

  Compared with

  Before-treatment baseline

  Main outcome

  24-hour GH profiles and height velocity

  Sample

  6 children aged 8 to 10.3 years with partial GH deficiency

  Authors' conclusion

  A biphasic GH response was seen, with no correlation to height velocity; possible mechanisms include GHRH antibodies, somatostatin changes or pituitary desensitization.

  Limitations

  Six children, no control group, continuous infusion rather than injections.

  DOI 10.1111/j.1651-2227.1993.tb12832.xPubMed 8329829

Reported side effects

• commonAnti-GHRH antibody formation [ref]
• commonTransient facial flushing [ref]
• commonInjection-site pain or irritation [ref] [ref]
• reportedTransient hyperlipidemia (with a related GHRH(1-29) analog) [ref]

Human safety data come mainly from pediatric GH-deficiency trials of 6-12 months; there are no long-term data for adult anti-aging use.

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.