Gonadorelin
Reproductive / Hormonal PeptideapprovedAlso known as: GnRH, Gonadotropin-Releasing Hormone, LHRH, Factrel, Lutrelef
The endogenous hypothalamic decapeptide that controls reproductive hormone release, used clinically for fertility treatment and diagnostics, and in TRT protocols to maintain testicular function.
Overview
Gonadorelin is a synthetic form of endogenous gonadotropin-releasing hormone (GnRH), a 10-amino acid peptide naturally produced by the hypothalamus. When administered in a pulsatile fashion, it stimulates the anterior pituitary to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which drive testosterone production and spermatogenesis in men, and ovulation and estrogen production in women. Gonadorelin has been used clinically since the 1980s for diagnostic testing of pituitary function, treatment of hypothalamic hypogonadism, induction of ovulation, and cryptorchidism. In modern TRT (testosterone replacement therapy) protocols, gonadorelin is increasingly used as an alternative to hCG for maintaining intratesticular testosterone production, testicular size, and fertility during exogenous testosterone use. Its pulsatile administration mimics natural GnRH secretion, while continuous administration paradoxically suppresses the reproductive axis (the basis for GnRH agonist drugs like leuprolide).
Mechanism of Action
Gonadorelin acts on the pituitary-gonadal axis: (1) Binds to GnRH receptors (GnRHR) on anterior pituitary gonadotrope cells; (2) Activates Gq/11 protein signaling, increasing intracellular calcium and PKC activation; (3) Stimulates synthesis and secretion of LH and FSH; (4) Pulsatile administration (every 60-120 min) maintains receptor sensitivity and physiological hormone release; (5) Continuous administration causes receptor downregulation and paradoxical suppression of LH/FSH; (6) LH stimulates testosterone production; FSH supports spermatogenesis; (7) Subject to negative feedback from sex steroids and inhibin.
Molecular Formula
C55H75N17O13
Molecular Weight
1182.29 g/mol
Sequence
pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2
Dosage Protocols
Dose Range
100mcg โ 200mcg
Frequency
Every other day or twice weekly
Route
subcutaneous
Cycle Length
Ongoing with TRT
Used alongside testosterone to maintain intratesticular testosterone, testicular volume, and fertility. Common replacement for hCG in modern TRT protocols. Some clinics use daily low-dose protocols.
Source: TRT clinic protocols and endocrinology practice
Side Effects
| Effect | Severity |
|---|---|
| Injection site reaction | mild |
| Headache | mild |
| Nausea | mild |
| Flushing | mild |
| Ovarian hyperstimulation (females) | severe |
| Hormonal flare (continuous use) | moderate |
Pros & Cons
Bioidentical to endogenous GnRH โ the most physiological approach to stimulating the HPG axis
FDA-approved with decades of clinical safety data
Effective at maintaining testicular function and fertility during TRT
Does not cause hCG-related estrogen spikes or desensitization of LH receptors
Very short half-life (~4 minutes) means pulsatile delivery is ideal but impractical for most users
Continuous or too-frequent dosing paradoxically suppresses the HPG axis
Less potent than hCG at directly stimulating testosterone in some protocols
Requires intact pituitary function โ ineffective in primary pituitary failure
Research Studies
Legal Status
FDA-approved (Factrel for diagnostic use; Lutrepulse for pulsatile therapeutic use โ discontinued). Available by prescription from compounding pharmacies. Used off-label in TRT protocols. Widely available as a research peptide.
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