Sermorelin: A better approach to management of adult-onset growth hormone insufficiency?

This review published in Clinical Interventions in Aging presents a detailed analysis of the advantages of sermorelin over direct recombinant growth hormone (GH) replacement in managing adult-onset growth hormone deficiency (AGHD). The author argues that physiological stimulation via GHRH is superior to exogenous GH replacement.

The central arguments of the review include:

Physiological advantages of sermorelin:

• Stimulates GH gene transcription in the pituitary, promoting endogenous synthesis and secretion
• Preserves the neuroendocrine GH axis, keeping feedback mechanisms intact
• Reproduces the physiological pulsatile pattern of GH release, rather than producing constant levels
• Maintains somatostatin regulation, preventing supraphysiological levels

Safety advantages:

• Lower risk of side effects associated with supraphysiological GH levels (edema, arthralgias, carpal tunnel syndrome)
• Preservation of the GH/IGF-I ratio within physiological ranges
• Potential reduction of the theoretical risk of tumor promotion associated with high-dose exogenous GH

Limitations of direct GH replacement:

• Suppression of the hypothalamic-pituitary axis through negative feedback
• Loss of the pulsatile and circadian GH pattern
• Greater difficulty in dose titration

The review concludes that sermorelin represents a "restorative" rather than "substitutive" approach, aligned with the modern trend of regenerative medicine. The author notes that, although sermorelin may be less potent than exogenous GH in terms of absolute IGF-I elevation, its ability to restore normal somatotropic axis physiology offers a more favorable risk-benefit profile for long-term use in aging.