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Gonadorelin

Also known as: GnRH · Gonadotropin-releasing hormone · Factrel · Lutrepulse · LHRH

113 views/week 567 citations 0 edits Updated 8/23/2026

Gonadorelin is a synthetic form of gonadotropin-releasing hormone (GnRH) that stimulates the pituitary to release LH and FSH, maintaining natural testosterone production and testicular function. It is widely used alongside TRT to prevent testicular atrophy and preserve fertility.

STRUCTURE

Molecular Composition

FORMULA

C₅₅H₇₅N₁₇O₁₃

MOL. WEIGHT

1,182.3 Da

CAS NUMBER

33515-09-2

TARGET

GnRH receptor

HALF-LIFE

2–4 min (IV)

SEQUENCE

10 amino acids

AMINO ACID CHAIN VISUALIZATION

pGlu-1

Protected N-terminal pGlu

—

NH-CO

His-2

GnRH receptor binding

—

NH-CO

Trp-3

Hydrophobic receptor contact

—

NH-CO

Ser-4

Backbone flexibility

—

NH-CO

Arg-8

Receptor anchoring residue

—

NH-CO

Gly-10

C-terminal amide (−NH₂)

SEQUENCEQ-H-W-S-R-G

MECHANISMS

How It Works

🔄

Pulsatile LH & FSH Release

Gonadorelin binds GnRH receptors on pituitary gonadotroph cells and triggers LH and FSH secretion via IP3/Ca²⁺ signalling. The pulsatile pattern (every 90–120 minutes) is critical — it maintains receptor sensitivity. Continuous exposure paradoxically downregulates GnRHR and suppresses gonadotropins, the mechanism exploited in GnRH agonist cancer therapy.

⚗️

Testicular Function Preservation During TRT

Exogenous testosterone suppresses hypothalamic GnRH, causing LH/FSH suppression and testicular atrophy. Gonadorelin administration twice weekly maintains LH/FSH signalling to Leydig and Sertoli cells, preserving intratesticular testosterone, testicular volume, and spermatogenesis throughout TRT.

⚖️

Physiological vs hCG Stimulation

Unlike hCG (which directly stimulates testicular LH receptors at supraphysiological levels), gonadorelin acts through the full hypothalamic-pituitary-gonadal axis. This produces more physiological LH pulses and avoids the oestradiol spike and receptor desensitisation associated with high-dose hCG.

🔬

Fertility Restoration in Hypogonadism

In hypogonadotropic hypogonadism, pulsatile gonadorelin delivery via pump restores the entire HPG axis, generating endogenous LH/FSH and sperm production — sometimes the only treatment capable of restoring fertility when the defect is hypothalamic rather than pituitary or gonadal.

OVERVIEW

Research Overview

Gonadorelin is a synthetic decapeptide identical to endogenous GnRH. It stimulates the anterior pituitary to release luteinising hormone (LH) and follicle-stimulating hormone (FSH), which in turn maintain endogenous testosterone production and spermatogenesis. Pulsatile administration is critical — continuous exposure leads to receptor downregulation and suppressed LH/FSH.

Mechanism of Action

Gonadorelin binds GnRH receptors on anterior pituitary gonadotroph cells, triggering IP3/DAG signalling and calcium influx, which stimulates LH and FSH release. Pulsatile dosing (every 90–120 minutes, or twice-weekly subcutaneous) mimics hypothalamic pulse frequency and maintains pituitary sensitivity.

DOSAGE

Dosage & Administration

INJECTABLE (SUBCUTANEOUS) — TRT SUPPORT

DOSE

100–250 mcg

FREQUENCY

Twice weekly

NOTES

Standard TRT adjunct protocol to maintain testicular function. Some protocols use 3× weekly. Inject on non-testosterone injection days for even HPG stimulation.

Calculate dose in Peptide Calculator

IV PULSATILE PUMP — HH TREATMENT

DOSE

25–75 mcg per pulse

FREQUENCY

Every 90–120 minutes (continuous pump)

NOTES

FDA-approved (Factrel/Lutrepulse) protocol for hypogonadotropic hypogonadism and ovulation induction. Requires programmable pump device.

Gonadorelin degrades rapidly at room temperature after reconstitution — refrigerate and use within 7 days. Very short half-life means twice-weekly SC injections are the minimum effective frequency. Generally well tolerated; injection-site reactions possible. Preferred over hCG by some TRT physicians for its physiological pulsatile mechanism and lack of oestradiol stimulation.

CYCLING

Cycle Duration Guide

ON CYCLE

Continuous (throughout TRT duration)

OFF CYCLE

Not typically cycled — used continuously alongside TRT

Gonadorelin is used as an ongoing TRT adjunct rather than in cycles. Discontinue only when TRT is stopped to allow full HPG axis recovery. For fertility-focused protocols, may be used as a bridge during TRT taper.

View full Cycle Guide →

NOTES

Research Notes

Used in TRT protocols to preserve testicular volume and sperm production. Typical research dose: 100–250 mcg subcutaneous twice weekly. Must be stored carefully — degrades rapidly at room temperature after reconstitution. Preferred over hCG by some clinicians for its more physiological pulsatile mechanism.

◆Quick Reference

FORMULAC₅₅H₇₅N₁₇O₁₃

MOL. WEIGHT1,182.3 Da

LENGTH10 amino acids

ORIGINSynthetic hypothalamic decapeptide; identical to endogenous GnRH

HALF-LIFE~2–4 minutes (IV); ~30 minutes (SC)

SOLUBILITYSoluble in sterile water; stable at pH 5–7

CAS NO.33515-09-2

STATUSResearch Only

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