Gonadorelin — Evidence & Status

Bottom line

Gonadorelin is synthetic gonadotropin-releasing hormone (GnRH), a decapeptide identical in sequence to the endogenous human hypothalamic hormone. It is approved for induction of ovulation in women with primary hypothalamic amenorrhea when administered in a pulsatile fashion (Lutrepulse, Canada/US limited availability), and as a veterinary reproductive agent in cattle (Factrel). The short half-life (~4 min) necessitates pump-based pulsatile delivery for fertility use. Gonadorelin is distinct from, and should not be confused with, GnRH agonist analogues (leuprolide, goserelin, triptorelin, nafarelin) that are modified for prolonged action and chemical castration.

Identity and composition

Field	Verified information
Preferred name	Gonadorelin
Key aliases	GnRH, LHRH, gonadotropin-releasing hormone; Lutrepulse (human), Factrel (veterinary)
Molecular/sequence identity	pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 (decapeptide)
Modifications/form	C-terminal amide; N-terminal pyroglutamyl; identical to endogenous human GnRH
Stable identifiers	PubChem CID 638793 (gonadorelin HCl); UNII Q2E1H3G52I
Identity caveats	Often confused with GnRH agonist analogues; distinct from leuprolide, goserelin, triptorelin, nafarelin, which contain D-amino acid substitutions and have longer half-lives

Development and approval status

Jurisdiction	Status and indication	Product/source	As of
Canada (Health Canada)	Approved; induction of ovulation in primary hypothalamic amenorrhea	Lutrepulse (Ferring) — commercially discontinued	2016 monograph
US (FDA)	Human: Lutrepulse was FDA-approved but commercially discontinued (not formally withdrawn). Veterinary: Factrel for cattle only (Zoetis)	Factrel (Zoetis) NADA 139-237	Lutrepulse commercially discontinued; Vet: 2014
EU (EMA)	Not actively marketed as human drug; historical GnRH diagnostic use	Various (diagnostic)	Not current

Mechanism and pharmacology

Endogenous agonist at the GnRH receptor on anterior pituitary gonadotrophs, triggering LH and FSH synthesis and secretion. Pulsatile administration mimics the natural hypothalamic secretory pattern, restoring gonadal function. Continuous administration causes receptor desensitisation (the basis of GnRH agonist therapy for prostate cancer). Half-life ~4 min; rapidly cleared.

Evidence by claim

Claim/indication	Stage	Grade	Best human evidence	Main result	Important limitations
Induction of ovulation, primary hypothalamic amenorrhea	Approved (Canada)	A	Controlled studies (Lutrepulse monograph)	68% ovulation rate with 5 µg i.v. q90 min	Requires pump; limited to specific diagnosis; product availability limited

Key studies

Study	Design/population	Exposure studied	Endpoints and result	Limitations
Lutrepulse clinical program	Open-label and controlled; women with primary hypothalamic amenorrhea	Pulsatile gonadorelin 1-20 µg s.c./i.v. q90 min	Ovulation in 68% (i.v. 5 µg regimen)	Small overall database; no longer widely available

Dose and administration evidence

Approved labeled regimen

The label summary below is product-, indication-, and jurisdiction-specific; consult the full current label and a licensed clinician/pharmacist.

Product: Lutrepulse (gonadorelin acetate) 3.2 mg/vial lyophilised
Route: Subcutaneous or intravenous via programmable pump
Dosing: 5 µg every 90 minutes
Response: Usually within 2-3 weeks
Continue for 2 weeks after ovulation to support corpus luteum

Studied regimens (not recommendations)

1-20 µg per pulse, various intervals studied.
Veterinary (Factrel): 100-200 µg IM in cattle for cystic ovaries / FTAI.

What is not established

No established or recommended human dose for any indication other than ovulation induction in primary hypothalamic amenorrhea.

Safety

Established label risks

Anaphylaxis reported with gonadorelin HCl (Factrel) — bronchospasm, tachycardia, flushing, urticaria.
Antibody formation in ~3% with s.c. administration (Factrel); may reduce efficacy.
Injection site reactions.
Ovarian hyperstimulation (rare with pulsatile vs. gonadotropins).

Human-study signals

Minimal systemic adverse effects at recommended doses.

Unknowns and product-quality risks

No long-term safety data beyond fertility treatment cycles.
No adequate studies in men.
Online "gonadorelin" products are not equivalent to pharmaceutical-grade Lutrepulse.

Interactions and special populations

Pregnancy: Used only as part of fertility treatment.
Ovarian hyperstimulation: Monitor; less common than with hMG.
Hepatic/renal: Not formally studied; no dose adjustment known.

Regulatory, compounding, and sport notes

US/Canada: Prescription only; Lutrepulse limited availability.
WADA: GnRH (gonadorelin) is explicitly prohibited at all times in males under S2.2.1; the List does not make that prohibition conditional on a demonstrated androgen effect. In female athletes under 18, GnRH analogues are included in the 2026 Monitoring Program, which is not prohibition.
Veterinary: Factrel approved for cattle only.
Compounding: Compounded GnRH exists but not FDA-reviewed; not interchangeable with approved product.

Evidence gaps

No adequately powered modern RCT for ovulation induction.
No data in hypogonadotropic hypogonadism in men.
Optimal pulse dose and frequency not formally re-evaluated.

Search notes

Databases and registries: DailyMed, Drugs@FDA, Health Canada DPD, PubMed, EMA
Search terms: gonadorelin, Lutrepulse, Factrel, pulsatile GnRH, hypothalamic amenorrhea
Last searched: 2026-08-06
Inclusion emphasis: Approved labels, clinical studies

Sources

Lutrepulse Product Monograph (Ferring, Canada). 2016. https://www.ferring.ca/media/1018/lutrepulse-pm-control-no-187199-32-mg-en_17may2016.pdf
DailyMed – FACTREL (gonadorelin HCl). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1451663c-b85a-4b45-8b27-6d572d0032f9
FDA FOI Summary – Factrel (NADA 139-237). https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/456
Health Canada DPD – Lutrepulse. https://health-products.canada.ca/dpd-bdpp/info?code=16273&lang=eng
PubChem CID 84866731 (gonadorelin HCl).