Gonadorelin

Gonadorelin is a synthetic peptide hormone whose amino acid sequence is identical to human gonadotropin-releasing hormone (GnRH) - a 10-amino-acid decapeptide from the hypothalamus (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2, molecular weight 1182 Da (free peptide)). Acting at the GnRH receptor (GnRHR) on gonadotroph cells of the anterior pituitary, it drives pulsatile LH and FSH release and is the central upstream signal of the hypothalamic-pituitary-gonadal (HPG) axis.

This entry documents gonadorelin because of its decades-long clinical role as the standard diagnostic probe of the HPG axis and as pulsatile therapy in reproductive endocrinology, even though the historical FDA-approved products Factrel and LutrePulse are no longer marketed in the United States.

How does gonadorelin work?

By activating the GnRH receptor, gonadorelin mimics physiological hypothalamic GnRH pulses and drives LH and FSH secretion. The pulse pattern is the decisive pharmacological variable:

• Pulsatile administration (every 60-120 min) stimulates the pituitary and preserves receptor sensitivity - the basis of the historical LutrePulse pump therapy for hypothalamic amenorrhea.
• Continuous exposure desensitizes and downregulates the GnRHR within days - paradoxically the mechanism behind long-acting GnRH super-agonists such as leuprolide.

What is gonadorelin used for?

• Diagnostic GnRH stimulation test: a single s.c./i.v. bolus (adults 100 µg, children 2 µg/kg) measures the LH peak (typical 60 ± 26 mIU/mL in men, peaking around 34 min) to assess gonadotroph reserve.
• Therapeutic pulsatile delivery: 5-20 µg per pulse every 90 min via s.c./i.v. portable pump for ovulation induction in hypothalamic amenorrhea (ovulation rates 70-94 % depending on dose and pulse frequency) and infertility due to hypogonadotropic hypogonadism.
• TRT adjunct: compounded gonadorelin is used - pharmacologically debated - alongside testosterone replacement therapy (TRT) to maintain HPG-axis activity and intratesticular testosterone production. Given the very short half-life, the rationale for once-daily s.c. injections is limited; only pulsatile delivery reliably replicates physiological LH/FSH patterns.

Half-life and pharmacokinetics

Gonadorelin has one of the shortest half-lives of any therapeutic peptide: distribution half-life 2-10 min, terminal half-life 10-40 min. The UK SmPC for gonadorelin 100 µg powder for solution reports a plasma half-life of about 4 min; degradation is by hydrolysis, excretion renal. A pulsatile pump is pharmacologically necessary for any sustained physiological LH/FSH response.

Evidence and current regulatory status

Factrel was approved in the United States for diagnostic use; LutrePulse later followed for pulsatile therapy. Both products have been withdrawn by their manufacturers; no FDA-approved gonadorelin product is currently marketed in the United States. Access today is via 503A compounding pharmacies (gonadorelin acetate is on the FDA Category 1 bulks list). In the EU/UK, gonadorelin is available as a prescription diagnostic. Recent publications confirm the continuing relevance of the GnRH stimulation test (Koca et al. 2024, PMID 39163851) and of pulsatile GnRH therapy in women with hypothalamic hypogonadotropic hypogonadism (Robin et al. 2026 expert opinion, PMID 41715131).

Practical considerations

• The very short half-life makes single daily s.c. injections pharmacologically questionable - only pulsatile delivery (pump) is physiologically meaningful.
• Compounded gonadorelin is not an FDA-approved finished drug - quality, sterility and dose accuracy vary between pharmacies.
• Diagnostic and therapeutic use always requires specialist endocrinology / gynaecology / urology follow-up; standard HPG workup (pregnancy, prolactin, thyroid) should be performed first.

To convert vial size, BAC-water volume and target dose into syringe ticks, use Peptipedia's injection calculator. General guidance on reconstitution and storage is collected in the Peptipedia guides.

Gonadorelin is a prescription-only medicine in the EU/UK; in the United States it is currently available only via 503A compounding. This entry is for information only and is not medical advice.