Gonadorelin
Also known as: GnRH, Gonadotropin-Releasing Hormone, LHRH, Factrel, Lutrepulse
Gonadorelin is the synthetic form of gonadotropin-releasing hormone (GnRH), a 10-amino acid peptide produced by the hypothalamus. It stimulates the pituitary gland to release LH and FSH, making it essential for fertility, testosterone production, and reproductive function. Used clinically for fertility treatment, hypogonadism diagnosis, and hormonal support.
Gonadorelin is a 1,182.29 Da research peptide. Gonadorelin is the synthetic form of gonadotropin-releasing hormone (GnRH), a 10-amino acid peptide produced by the hypothalamus. It stimulates the pituitary gland to release LH and FSH, making it essential for fertility, testosterone production, and reproductive function. Used clinically for fertility treatment, hypogonadism diagnosis, and hormonal support.
Also called: GnRH, Gonadotropin-Releasing Hormone, LHRH
1,182.29
Molecular Weight
Daltons
3
Strong Evidence
benefits
5
Studies Cited
peer-reviewed
100-200
Typical Dose
mcg
Overview
Gonadorelin is a synthetic decapeptide identical to endogenous gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone-releasing hormone (LHRH). The natural hormone is produced by GnRH neurons in the hypothalamus and released in a pulsatile fashion into the hypothalamic-pituitary portal blood system, where it acts on gonadotroph cells in the anterior pituitary gland to stimulate the synthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These gonadotropins then act on the gonads; LH drives testosterone production in Leydig cells (males) and ovulation (females), while FSH supports spermatogenesis (males) and follicular development (females). Gonadorelin has been used clinically as Factrel (for diagnostic testing of pituitary gonadotroph function) and Lutrepulse (for pulsatile GnRH therapy in hypothalamic amenorrhea). In the context of peptide therapy and men's health, gonadorelin is used to stimulate endogenous LH/FSH production to maintain or restore testicular function, particularly during or after testosterone replacement therapy (TRT) to preserve fertility and testicular volume. It is increasingly used as an alternative to human chorionic gonadotropin (hCG) for maintaining the HPG axis.
Key Takeaways: Gonadorelin
- Strongest evidence supports Gonadorelin for endogenous lh/fsh stimulation and pituitary function diagnostic
- Research doses typically range from 100 to 200 mcg via subcutaneous injection
- 3 benefits with strong evidence, 2 moderate, 0 preliminary
- Half-life: ~2-4 minutes (very rapidly degraded by endopeptidases)
- 5 cited research studies in this guide
Mechanism of Action
Gonadorelin binds to the GnRH receptor (GnRHR), a Gq/11-coupled GPCR on anterior pituitary gonadotroph cells. Receptor activation triggers the phospholipase C (PLC)/inositol trisphosphate (IP3)/diacylglycerol (DAG) cascade, mobilizing intracellular calcium and activating protein kinase C (PKC). This drives the transcription and secretion of both LH and FSH. The pulsatile pattern of GnRH release is critical for normal gonadotropin production, different pulse frequencies preferentially stimulate LH versus FSH. High-frequency pulses (every 60-90 minutes) favor LH secretion, while lower-frequency pulses (every 2-4 hours) favor FSH. Critically, continuous (non-pulsatile) GnRH exposure causes GnRH receptor downregulation and desensitization, leading to suppression of LH/FSH — this is the mechanism exploited by GnRH agonist drugs (leuprolide, goserelin) used for prostate cancer, endometriosis, and precocious puberty. For therapeutic gonadorelin use, pulsatile or intermittent administration is essential to maintain gonadotroph responsiveness. In males on TRT, gonadorelin stimulates endogenous LH production to maintain Leydig cell activity, intratesticular testosterone, and spermatogenesis, functions that are suppressed by exogenous testosterone through HPG axis negative feedback.
Research Benefits
Gonadorelin at a Glance
Gonadorelin binds to the GnRH receptor (GnRHR), a Gq/11-coupled GPCR on anterior pituitary gonadotroph cells.
Endogenous LH/FSH Stimulation
Strong EvidenceStimulates the pituitary to produce LH and FSH naturally, supporting testosterone production and spermatogenesis through the endogenous HPG axis.
Pituitary Function Diagnostic
Strong EvidenceFDA-approved (as Factrel) for evaluating pituitary gonadotroph reserve; the GnRH stimulation test helps differentiate hypothalamic from pituitary causes of hypogonadism.
Hypothalamic Amenorrhea Treatment
Strong EvidencePulsatile GnRH therapy (Lutrepulse) is the physiological treatment for hypothalamic amenorrhea, restoring normal menstrual cycles and fertility.
Fertility Preservation During TRT
Moderate EvidenceMaintains testicular function and spermatogenesis in men on testosterone therapy by preserving intratesticular testosterone levels through LH stimulation.
Testicular Volume Maintenance
Moderate EvidencePrevents testicular atrophy associated with TRT by maintaining gonadotropin-driven Leydig and Sertoli cell activity.
Research Dosing Protocols
Research Purposes Only: All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
| Research Protocol | Dose Range | Route |
|---|---|---|
| HPG axis support (men's health) | 100–200 mcg | Subcutaneous injection |
| GnRH stimulation test (diagnostic) | 100–100 mcg | Intravenous or subcutaneous |
| Pulsatile therapy (hypothalamic amenorrhea) | 5–20 mcg per pulse | IV or SC via pulsatile pump (every 60-120 minutes) |
Frequency
2-3 times daily (SC for HPG support); pulsatile every 60-120 min (pump therapy)
Timing
Spaced throughout the day to mimic pulsatile release; continuous infusion for pump therapy
Cycle Length
Ongoing during TRT; diagnostic: single dose; pump therapy: until ovulation/conception
Research Notes
- 1Pulsatile administration is essential — continuous dosing causes receptor downregulation and LH/FSH suppression.
- 2Very short half-life (~2-4 minutes); requires frequent dosing or pulsatile pump.
- 3Used as an alternative to hCG for maintaining testicular function during TRT.
- 4The GnRH stimulation test measures LH/FSH response at 15, 30, 45, 60, and 120 minutes post-injection.
- 5Clomiphene citrate and enclomiphene are oral alternatives that work through the same pathway (anti-estrogen → increased GnRH pulsatility).
- 6Monitor LH, FSH, testosterone, and semen parameters when used for fertility preservation.
Reconstitution Guide
Standard Reconstitution
Vial Size
0.1 mg
Bacteriostatic Water
1 mL
Concentration
1 mcg
per 0.1 mL (10 units)
Step-by-Step Guide
Gather Materials
Gonadorelin vial, bacteriostatic water, alcohol swabs, insulin syringes.
Equilibrate Temperature
Remove the vial from storage and allow it to reach room temperature (5-10 minutes).
Sanitize
Swab the rubber stopper of both the peptide vial and bacteriostatic water vial with alcohol.
Draw Water
Draw 1 mL of bacteriostatic water into a syringe.
Add Water to Vial
Insert the needle into the peptide vial and direct the water stream against the glass wall — not directly onto the powder.
Mix Gently
Swirl the vial gently until the powder is fully dissolved. Never shake. The solution should be clear and colorless.
Store Properly
Refrigerate at Refrigerated (2-8°C) after reconstitution. 14 days refrigerated after reconstitution.
Storage Temperature
Refrigerated (2-8°C) after reconstitution
Shelf Life
14 days refrigerated after reconstitution
Important Notes
- •Reconstitute with provided diluent or bacteriostatic water.
- •Gonadorelin is a relatively fragile peptide, use promptly after reconstitution.
- •Protect from light and heat.
- •Factrel kit includes specific diluent.
Gonadorelin Dosing Calculator
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Gonadorelin Reconstitution Calculator
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Safety & Side Effects
Reported Side Effects
- !Injection site reactions (common with frequent SC administration)
- !Headache (occasional)
- !Nausea (infrequent)
- !Flushing
- !Abdominal discomfort
- !Multi-follicular response in females (risk of multiple pregnancy with pulsatile therapy)
- !Ovarian hyperstimulation syndrome (OHSS) in females (rare but serious with pulsatile therapy)
- !Generally well tolerated for short-term diagnostic use
Potential Interactions
- ⚡Testosterone and androgens suppress GnRH response (negative feedback) — gonadorelin is used to counteract this.
- ⚡GnRH agonists (leuprolide, goserelin): opposite approach, continuous agonism causes downregulation.
- ⚡GnRH antagonists (cetrorelix, degarelix): directly block GnRH receptor; contraindicated with gonadorelin.
- ⚡Clomiphene/enclomiphene: works upstream of GnRH (blocks estrogen negative feedback to increase GnRH).
- ⚡hCG: acts directly on LH receptor — alternative to gonadorelin for Leydig cell stimulation.
- ⚡Dopamine agonists may suppress GnRH/LH pulsatility.
Important: Side effects and interactions listed here are compiled from published research and community reports. This is not a complete list. No formal drug interaction studies have been conducted for most research peptides. Always consult a qualified healthcare provider.
Research Studies
The following studies are referenced in this profile. PubMed IDs are provided where available for independent verification.
Pulsatile GnRH therapy for hypothalamic amenorrhea
Demonstrated pulsatile GnRH restores normal LH/FSH pulsatility, ovulation, and fertility in women with hypothalamic amenorrhea, establishing the physiological basis for GnRH replacement therapy.
GnRH for preservation of spermatogenesis during TRT
Reviewed gonadorelin as an alternative to hCG for maintaining spermatogenesis and testicular volume in men on testosterone therapy, with clinical outcomes data.
The GnRH pulse generator: physiology and clinical implications
thorough review of GnRH neurobiology, pulsatile secretion mechanisms, and the critical importance of pulse frequency for differential LH/FSH regulation.
GnRH stimulation test for hypogonadism diagnosis
Review of the GnRH stimulation test protocol and interpretation, showing how LH/FSH response patterns differentiate hypothalamic, pituitary, and gonadal causes of hypogonadism.
Comparison of hCG and GnRH for intratesticular testosterone maintenance
Compared hCG and GnRH-based approaches for maintaining intratesticular testosterone and fertility during TRT, providing clinical guidance for hormonal optimization.
Note: This is not an exhaustive list of all published research. Studies are selected for relevance and quality. Click PubMed IDs to verify sources independently. Inclusion does not imply endorsement of the peptide for any clinical use.
Frequently Asked Questions
Gonadorelin is synthetic GnRH; the hypothalamic hormone that tells your pituitary to produce LH and FSH. It is used for fertility, maintaining testicular function during TRT, and diagnostic testing of pituitary function.
Exogenous testosterone suppresses the HPG axis, reducing LH/FSH and causing testicular atrophy and infertility. Gonadorelin stimulates endogenous LH production to maintain Leydig cell activity, intratesticular testosterone, and spermatogenesis despite exogenous testosterone.
hCG directly activates the LH receptor on Leydig cells (bypassing the pituitary). Gonadorelin stimulates the pituitary to produce LH/FSH naturally. Gonadorelin maintains the full HPG axis while hCG only supports the gonadal level. Both preserve testicular function during TRT.
Continuous GnRH exposure causes GnRH receptor downregulation, the pituitary stops responding and LH/FSH decrease. This is actually how GnRH agonist drugs (leuprolide) work for prostate cancer. Therapeutic gonadorelin must be given intermittently to maintain pulsatile signaling.
Gonadorelin was FDA-approved as Factrel (diagnostic) and Lutrepulse (pulsatile pump for hypothalamic amenorrhea), though some formulations have been discontinued. It is available through compounding pharmacies for hormone optimization protocols.
Research & Educational Use Only
All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
The information presented here is compiled from published research studies and is intended for informational purposes only. Individual results may vary. Always consult with a licensed healthcare provider.