Is oral sermorelin (growth hormone-releasing hormone (GHRH) analogue) effective for growth hormone stimulation?

Oral Sermorelin is Not Effective for Growth Hormone Stimulation

Oral sermorelin is not effective for growth hormone stimulation due to poor bioavailability through the gastrointestinal tract, and parenteral administration (subcutaneous or intravenous) is required for clinical efficacy.

Mechanism and Administration Routes

Sermorelin is a 29-amino acid analogue of human growth hormone-releasing hormone (GHRH) that stimulates the pituitary gland to secrete growth hormone 1. However, its effectiveness is highly dependent on the route of administration:

• Oral administration: Not effective due to:

  • Peptide degradation in the gastrointestinal tract
  • Poor absorption across intestinal mucosa
  • First-pass metabolism in the liver

• Effective routes:

  • Subcutaneous: 30 μg/kg bodyweight daily (typically at bedtime) 1
  • Intravenous: 1 μg/kg bodyweight (primarily for diagnostic testing) 1, 2
  • Intranasal: Limited bioavailability (only 3-5%) but can be effective at higher doses (approximately 50 μg/kg) 2

Evidence for Efficacy by Route

Parenteral Administration

Subcutaneous and intravenous sermorelin have demonstrated efficacy:

• Subcutaneous sermorelin at 30 μg/kg bodyweight given at bedtime has shown significant increases in height velocity in prepubertal children with idiopathic growth hormone deficiency 1
• Intravenous sermorelin at 1 μg/kg bodyweight effectively stimulates acute GH release for diagnostic purposes 1, 2
• Continuous infusion of sermorelin has shown growth effects, though less robust than standard GH therapy 3

Oral Administration

No clinical evidence supports the efficacy of oral sermorelin for growth hormone stimulation. The guidelines for growth hormone treatment consistently recommend parenteral administration of growth hormone and its secretagogues 4, 5.

Comparison with Other GH Stimulation Methods

• Sermorelin vs. Somatropin (GH): Direct comparison studies show that sermorelin produces less growth velocity increase than somatropin at equivalent doses 1, 3
• Sermorelin vs. Other GH Secretagogues: Some newer GH secretagogues like ipamorelin derivatives have shown limited oral bioavailability (10-20%) in animal studies, but this is still insufficient for reliable clinical use 6

Monitoring and Clinical Considerations

If using parenteral sermorelin, monitoring should include:

• Growth and development parameters (height velocity, skeletal maturation) 5
• Metabolic parameters (glucose, insulin, thyroid function) 5
• IGF-1 levels to assess treatment response 5
• Potential adverse effects:
  • Transient facial flushing
  • Pain at injection site
  • Development of GHRH antibodies with prolonged use 3

Clinical Implications

For patients requiring growth hormone stimulation, clinicians should:

1. Use only parenteral forms of sermorelin (subcutaneous or intravenous)
2. Consider that even with proper administration, sermorelin appears less effective than direct GH replacement 3
3. Be aware that the FDA recommends GH therapy administered at 0.045-0.05 mg/kg per day by daily subcutaneous injections for children with growth disorders 4

Conclusion

Oral sermorelin should not be used for growth hormone stimulation as there is no evidence supporting its efficacy via this route. Patients requiring growth hormone stimulation should receive parenteral sermorelin or, preferably, standard growth hormone therapy which has more robust clinical evidence.