Growth Hormone Secretagogues

Two complementary pathways drive GH release. GHRH analogues (sermorelin, tesamorelin, CJC-1295) act on the GHRH receptor on pituitary somatotrophs to stimulate GH synthesis and secretion. GHRPs (ipamorelin, GHRP-2, GHRP-6, hexarelin) activate the ghrelin receptor (GHS-R1a) to amplify GH pulse amplitude. Combining a GHRH analogue with a GHRP creates a synergistic effect — the GHRH primes the pituitary while the GHRP amplifies the release, producing GH pulses 2-3x larger than either alone.

CJC-1295 (with DAC) — a long-acting GHRH analogue using a Drug Affinity Complex to bind serum albumin, extending half-life to ~8 days. CJC-1295 (no DAC / Mod GRF 1-29) — a shorter-acting GHRH analogue (half-life ~30 min) preferred for more physiological pulsatile release. Ipamorelin — the most selective GHRP with minimal impact on cortisol, prolactin, or hunger. GHRP-6 — a potent GHRP that strongly stimulates appetite via ghrelin receptor activation. Sermorelin — a GHRH analogue that is one of the few GH secretagogues with FDA approval history (Geref). Tesamorelin — FDA-approved for HIV-associated lipodystrophy (Egrifta). MK-677 (Ibutamoren) — an oral non-peptide GHS-R1a agonist with ~24-hour half-life.

The most common GH secretagogue protocol combines a GHRH analogue with a GHRP for synergistic release. CJC-1295 (no DAC) + Ipamorelin is the most popular combination, administered subcutaneously before bed to coincide with natural nocturnal GH surges. Timing matters — GH release is blunted by food intake (especially carbohydrates and fats), so dosing on an empty stomach or during fasting windows maximizes response. IGF-1 blood levels are the primary biomarker used to assess protocol effectiveness.

Sermorelin and tesamorelin have FDA-approved indications with supporting clinical trial data. MK-677 has multiple RCTs showing sustained IGF-1 elevation but failed to gain FDA approval. Ipamorelin has phase II data for post-surgical recovery. Most GHRP protocols are based on pharmacokinetic data and community experience rather than large clinical trials. Common side effects include water retention, tingling/numbness, increased hunger (GHRP-6), and potential insulin resistance with prolonged high-dose use. Long-term GH elevation theoretically increases cancer risk, though this remains debated.