Growth hormone secretagogues stimulate the pituitary to release endogenous GH rather than replacing it with exogenous GH. This preserves the pulsatile release pattern and feedback regulation. But the approach requires attention to timing, fasting state, and cycling to maintain receptor sensitivity.

Peptide selection

GH secretagogues fall into two mechanistic categories that work synergistically:

GHRH analogs (amplify GH pulse amplitude):

CJC-1295 (with or without DAC)
Sermorelin
Tesamorelin

Ghrelin mimetics / GHRPs (initiate GH pulse):

Ipamorelin (cleanest — minimal cortisol/prolactin elevation)
GHRP-2 (stronger GH release, mild hunger increase)
GHRP-6 (strong GH release, significant hunger increase)
Hexarelin (strongest GH release, but desensitizes fastest)

Combining one GHRH analog + one GHRP produces synergistic GH release — roughly 3–5x greater than either alone.

Standard protocol: CJC-1295 + Ipamorelin

This is the most widely used combination due to its clean side-effect profile.

Dose: CJC-1295 (no DAC), 100 mcg + Ipamorelin, 100–200 mcg per injection

Route: Subcutaneous

Frequency: 1–2 times daily

Timing:

Primary dose: 30 minutes before bed, on an empty stomach (2+ hours post-meal). GH release peaks during early slow-wave sleep — timing the secretagogue pulse to coincide with natural nocturnal GH release amplifies the physiological pattern
Optional second dose: Morning upon waking, fasted. This captures the natural early-morning GH pulse window

Cycle length: 12–16 weeks on, 4–8 weeks off

Fasting requirement: Critical. Insulin and free fatty acids blunt GH release. The pre-injection fasting window must be maintained — no carbohydrates or fats for 2 hours before and 30 minutes after injection.

Alternative protocols

Sermorelin monotherapy

For individuals preferring a single-peptide approach or those with prior GHRP sensitivity concerns.

Dose: Sermorelin, 200–300 mcg

Timing: Pre-sleep, fasted (same timing principles)

Cycle: 3 months on, 1 month off

GHRP-2 or GHRP-6 (short cycles)

Higher-potency options for specific goals (body recomposition, injury recovery).

Dose: GHRP-2, 100–200 mcg or GHRP-6, 100–200 mcg (combined with a GHRH analog)

Cycle: 8–12 weeks maximum — desensitization risk is higher than with Ipamorelin

Note: GHRP-6 causes significant hunger via ghrelin activation. This is a feature or a bug depending on the goal (bulking vs. cutting).

Hexarelin (pulse cycles)

Strongest GH release but fastest desensitization. Used for short, intensive protocols.

Dose: 100–200 mcg

Cycle: 4–6 weeks maximum, then 4+ weeks off

Monitoring: IGF-1 levels — if they stop rising despite continued use, desensitization has occurred

Desensitization management

Receptor desensitization is the primary reason for cycling. Signs:

Diminishing subjective effects (sleep quality, recovery)
IGF-1 plateau or decline despite continued dosing
Reduced injection-site warmth/flush (a marker of acute GH release)

Prevention strategies:

Adhere to cycle lengths — don't extend past 16 weeks
Use lower-potency secretagogues (Ipamorelin > GHRP-2 > Hexarelin) for longer cycles
The off-cycle period allows receptor upregulation and sensitivity restoration

Monitoring

IGF-1 levels: Baseline, week 8, and end of cycle. IGF-1 is the best proxy for sustained GH elevation. Target: upper-normal range for age (not supraphysiological)
Fasting glucose and HbA1c: GH is counter-regulatory to insulin. Monitor for glucose elevation, especially in individuals with metabolic risk factors
Sleep quality: Subjective assessment. Improved deep sleep is often the first and most noticeable effect
Body composition: Track lean mass and fat mass (DEXA or bioimpedance) at baseline and end of cycle

Safety considerations

Insulin sensitivity: GH elevation can reduce insulin sensitivity. If fasting glucose rises above 100 mg/dL, reduce dose or add structured exercise (which improves insulin sensitivity)
Joint pain or carpal tunnel symptoms: Indicate GH effect is present but may be excessive. Reduce dose
Water retention: Mild fluid retention is common and resolves with dose adjustment or cycling off
Cancer screening: Ensure age-appropriate cancer screening is current before starting. GH/IGF-1 elevation is contraindicated in individuals with active malignancy