Ipamorelin
The selective GH secretagogue without cortisol or prolactin elevation
Definition
Ipamorelin is a pentapeptide GH secretagogue that acts selectively on the ghrelin receptor (GHS-R1a), inducing pulsatile endogenous release of GH from the pituitary without elevating prolactin, cortisol, ACTH, or LH/FSH — a selectivity profile superior to earlier secretagogues like GHRP-2 and GHRP-6. This selectivity makes it the peptide of choice in longevity protocols seeking GH benefits without unwanted endocrine side effects.
Detailed explanation
Mechanism of action: Ipamorelin binds to the GHS-R1a receptor (originally identified as the ghrelin receptor) on the pituitary, activating intracellular pathways (PKC, phospholipase C) that cause pulsatile release of stored GH. The preserved pulsatility — unlike exogenous GH that produces non-physiological sustained levels — protects tissue sensitivity to GH and prevents negative regulation.
Typical protocols: Ipamorelin alone: 200-300 mcg subcutaneous 1-2 times daily (ideal before bedtime and, optionally, fasting). Combined with CJC-1295 (without DAC): the most-used combination — CJC acts via the GHRH pathway and Ipamorelin via the ghrelin pathway, producing synergy with lower doses of each. Combined with Tesamorelin: less common but powerful strategy for visceral fat reduction.
Documented effects: improved deep sleep (N3), IGF-1 increase (50-100%), improved body composition (more lean mass, less visceral fat), accelerated post-exercise recovery, improved skin elasticity, and erectile function.
Recommended monitoring: IGF-1 every 6-8 weeks, fasting glucose and insulin (watch mild elevation), TSH (secretagogues can subtly modulate thyroid function).
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