Sermorelin
Also known as: GRF 1-29, Geref, Growth Hormone Releasing Factor
The first synthetic GHRH analog, consisting of the first 29 amino acids of natural GHRH. Previously FDA-approved for pediatric growth hormone deficiency, now widely used in anti-aging medicine.
Half-Life
10-20 minutes
Typical Dose
100-300 mcg
Frequency
Once daily (bedtime)
Routes
Subcutaneous
Overview
Sermorelin is a synthetic peptide consisting of the first 29 amino acids of the naturally occurring 44 amino acid Growth Hormone Releasing Hormone (GHRH). It was the first GHRH analog to receive FDA approval (1997) under the brand name Geref for diagnostic testing and treatment of growth hormone deficiency in children.
Although Geref was discontinued in 2008 for commercial reasons (not safety concerns), sermorelin remains one of the most widely used peptides in anti-aging and wellness medicine due to its long safety history and physiological approach to GH enhancement.
Key Characteristics
- Origin: Synthetic GHRH fragment (amino acids 1-29)
- Classification: Growth Hormone Releasing Hormone analog
- Historical FDA Status: Previously approved (Geref, 1997-2008)
- Current Status: Compounding pharmacies, research
- Unique Feature: Decades of safety data, physiological GH release
Why 29 Amino Acids?
Research showed that:
- Full GHRH is 44 amino acids
- Only the first 29 are needed for biological activity
- Amino acids 1-29 bind the GHRH receptor fully
- Remaining 15 amino acids add stability, not function
- Shorter peptide = easier to manufacture
Mechanism
Primary Mechanisms
1. GHRH Receptor Binding
Sermorelin mimics natural GHRH:
- Binds to GHRH receptors on pituitary somatotrophs
- Activates adenylyl cyclase
- Increases intracellular cAMP
- Triggers growth hormone release
2. Pulsatile GH Release
Unlike synthetic HGH:
- Stimulates natural pulsatile secretion
- Works with body's feedback systems
- Maintains circadian rhythm of GH
- Doesn't suppress endogenous production
3. Preserved Negative Feedback
Important safety feature:
- Somatostatin still regulates release
- Body can limit excessive GH
- Self-limiting mechanism
- Reduces risk of supraphysiological levels
4. Secondary IGF-1 Increase
Downstream effects:
- Liver produces IGF-1 in response to GH
- Creates systemic anabolic effects
- Supports tissue repair and growth
- Modulates metabolism
Research
Research Note: Sermorelin has extensive safety data from its years as an FDA-approved medication, plus decades of clinical use in anti-aging medicine.
Historical Clinical Trials
Pediatric Growth Hormone Deficiency
Geref trials showed:
- Increased growth velocity in GH-deficient children
- Elevated GH and IGF-1 levels
- Good tolerability
- Effective at stimulating pituitary function
Adult GH Deficiency
Off-Label Use Data
Clinical observations show:
- Improved body composition
- Enhanced sleep quality
- Better recovery and energy
- Favorable safety profile
Anti-Aging Applications
Wellness Medicine Use
Widely observed benefits:
- Improved sleep architecture
- Better skin elasticity
- Enhanced lean body mass
- Reduced visceral fat
- Improved sense of well-being
Sleep Enhancement
Deep Sleep Benefits
Research indicates:
- Increased slow-wave sleep duration
- Enhanced sleep quality
- Better nocturnal GH secretion
- Improved recovery during sleep
This is why bedtime dosing is preferred.
Comparison to Newer GHRH Analogs
| Feature | Sermorelin | CJC-1295 | Tesamorelin | |---------|-----------|----------|-------------| | Half-life | 10-20 min | 30 min (No DAC) | 26-38 min | | Stability | Lower | Higher | Higher | | Dosing | Daily | Daily | Daily | | FDA History | Yes | No | Yes (current) | | Cost | Lower | Moderate | Higher |
Dosing
Disclaimer: Sermorelin is available through compounding pharmacies for wellness use. The following information is for reference. Always follow prescriber guidance.
Research Protocols
| Protocol | Dose | Frequency | Duration |
|---|---|---|---|
| Anti-Aging / Wellness | 100-300 mcg | Once daily (bedtime) | Ongoing |
| With Ipamorelin | 100-200 mcg each | Once daily (bedtime) | 8-12 weeks |
| Higher Dose | 300-500 mcg | Once daily (bedtime) | 8-12 weeks |
| Twice Daily | 100-200 mcg | Morning + bedtime | 8-12 weeks |
Administration Notes
Timing
- Bedtime dosing preferred (syncs with natural nocturnal GH pulse)
- Take on empty stomach
- No food for 2 hours before
- No food for 30-60 minutes after
The "Fasted" Rule
- Insulin antagonizes GH release
- Carbohydrates spike insulin
- Fasting maximizes GH response
- Critical for effectiveness
Why Bedtime?
- Natural GH pulse occurs during deep sleep
- Sermorelin amplifies this natural rhythm
- Maximizes recovery benefits
- Minimizes daytime side effects
Reconstitution
- Use bacteriostatic water
- Gentle swirling, no shaking
- Typical: 15mg vial + 5ml water = 3mg/ml
- Store refrigerated (2-8°C)
- Use within 2-4 weeks
Synergy & Stacking
The Classic Stack
Sermorelin + Ipamorelin
Most popular combination:
- GHRH (sermorelin) + GHRP (ipamorelin)
- Synergistic 3-10x greater GH release
- Clean side effect profile
- Foundation of many wellness protocols
Common Combinations
Sermorelin + GHRP-2
For stronger release:
- More potent than ipamorelin combination
- May increase appetite
- Slightly more side effects
- Greater GH pulse
Sermorelin + BPC-157
Recovery focus:
- Sermorelin for systemic GH benefits
- BPC-157 for localized tissue repair
- Complementary mechanisms
- Popular for injury recovery
Timing Considerations
When stacking:
- Can inject together (same syringe)
- Both should be fasted
- Bedtime preferred for both
- Start with lower doses
Safety
Known Side Effects
Common (generally mild)
- Injection site reactions (redness, swelling)
- Flushing or warmth
- Headache (temporary)
- Dizziness
- Hyperactivity (if taken too late)
Rare
- Allergic reactions
- Swelling at injection site
- Chest tightness (very rare)
Contraindications
Avoid or use with extreme caution if:
- Active malignancy or cancer history
- Diabetic retinopathy
- Pregnancy or breastfeeding
- Under 18 years (unless GH deficient with medical supervision)
Important: Like all GH-enhancing compounds, sermorelin increases IGF-1 which may theoretically promote tumor growth. Those with cancer history should avoid use.
Drug Interactions
- May interact with glucocorticoids
- Caution with thyroid medications
- Monitor with diabetes medications
- Generally safe with most common medications
Long-Term Safety
Sermorelin's advantages:
- Decades of clinical use
- Self-limiting via negative feedback
- Doesn't cause supraphysiological GH
- Maintains pituitary function
- No exogenous GH suppression
Monitoring
Baseline Assessments
- IGF-1 level
- Comprehensive metabolic panel
- Fasting glucose
- Body composition (optional but helpful)
During Treatment
- IGF-1 (every 3-6 months)
- Fasting glucose periodically
- Sleep quality assessment
- Body composition changes
Signs of Adequate Response
- Improved sleep quality
- Better recovery
- Improved skin appearance
- Body composition improvements
Regulatory
Current Status
| Region | Status | |--------|--------| | United States | Discontinued as branded drug; available via compounding | | WADA | Strictly Prohibited (S2 category) | | Compounding | Widely available through compounding pharmacies | | Detection | Detectable in anti-doping tests |
Legal Considerations
- Legally available via prescription from compounding pharmacies
- Requires medical evaluation and prescription
- Not controlled substance
- Athletes: Strictly banned in and out of competition
Clinical Outlook
Sermorelin remains relevant because:
- Excellent long-term safety data
- Lower cost than newer alternatives
- Physiological approach to GH enhancement
- Foundation for combination protocols
- Widely accessible through compounding
- Time-tested in anti-aging medicine