What GH secretagogues actually do
Growth hormone secretagogues (GHS) are a class of peptides that stimulate the pituitary gland to release growth hormone in a pulsatile, physiologically normal pattern. They are not the same as exogenous recombinant HGH. The distinction is critical: exogenous GH suppresses endogenous production via negative feedback; secretagogues preserve and amplify the body's own secretion rhythm.
Two receptor systems are relevant. GHRH-receptor agonists (CJC-1295, sermorelin, tesamorelin) mimic growth hormone-releasing hormone from the hypothalamus. Ghrelin-receptor agonists (ipamorelin, hexarelin, MK-677) bind the GHS-R1a receptor, driving a distinct pituitary signal. Stacking one from each class produces additive pulsation without equivalent feedback blunting.
CJC-1295 vs. sermorelin — duration and potency
Sermorelin is the shortest-acting option: a 29-amino-acid GHRH analog with a half-life of ten to twenty minutes. It mimics the natural, brief hypothalamic pulse. CJC-1295 extends that pulse via a drug affinity complex (DAC) that binds serum albumin, extending half-life to seven to ten days per dose. That longevity is both its advantage and its risk — if you react poorly, the signal persists.
For patients new to GHS therapy, sermorelin's short half-life makes it the lower-risk entry point. CJC-1295 is reserved for patients who have tolerated a shorter-acting analog and want sustained IGF-1 elevation with weekly rather than nightly dosing.
| Compound | Class | Half-life | Dosing schedule | Practical |
|---|---|---|---|---|
| Sermorelin | GHRH analog | 10–20 min | Nightly SC | Best starting point; short half-life, reversible |
| CJC-1295 (DAC) | GHRH analog | 7–10 days | 1–2× weekly SC | Sustained IGF-1 elevation; less forgiving if poorly tolerated |
| Ipamorelin | GHS-R agonist | 2 hours | Nightly SC | Selective GH pulse; minimal cortisol/prolactin elevation |
Why GHRH + GHS stacks work
The clinical rationale for combining a GHRH analog with a ghrelin-mimetic is synergy at the pituitary level. The two receptor systems amplify each other: GHRH primes somatotrophs (GH-secreting pituitary cells) and the ghrelin signal then triggers a larger-than-normal release. The IGF-1 response to the CJC-1295 + ipamorelin combination exceeds either agent alone by a factor of 2–3× in clinical use.
Ipamorelin is the preferred GHS-R agonist because it is highly selective for GH secretion with minimal effect on cortisol and prolactin — a critical safety advantage over older ghrelin mimetics like GHRP-2 and GHRP-6.
Monitoring: IGF-1 is the signal
IGF-1 (insulin-like growth factor-1) is the primary biomarker for GHS therapy response. It is produced in the liver downstream of GH stimulation and has a half-life of fifteen to twenty hours, making it a stable, integrated measure of GH-axis activity — unlike GH itself, which pulses and is hard to capture.
Baseline IGF-1 is drawn before the first dose. At 90 days, we target an IGF-1 in the upper quartile of age-adjusted reference range — not supraphysiologic. If IGF-1 exceeds the upper limit of normal, dose is reduced. If response is sub-optimal, the protocol is reviewed for compliance and timing.
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