Gonadorelin

Sexual Health

aka GnRH · LHRH · gonadorelin acetate

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Formula

MW (Da)

Half-life

~2–10 min (IV)

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Overview

Gonadorelin is the native decapeptide gonadotropin-releasing hormone (GnRH). Among the compounds in this report it has the clearest human efficacy track record, because pulsatile dosing directly replaces deficient hypothalamic GnRH in selected patients, most notably women with hypothalamic amenorrhea.

Mechanism

GnRH acts on the type I GnRH receptor on pituitary gonadotrophs. The receptor is primarily Gq/G11-coupled, activating phospholipase C, generating IP3 and DAG, mobilizing intracellular Ca2+, activating PKC, and promoting LH and FSH secretion. Additional signaling branches include phospholipase D, phospholipase A2, and ERK-linked transcriptional programs. Importantly, physiologic benefit depends on pulsatile exposure; prolonged continuous receptor activation promotes desensitization and can suppress gonadotropin output.

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Reported benefits

Restored ovulation in hypothalamic amenorrhea

In a multicenter trial of 109 women with primary or secondary hypothalamic amenorrhea, pulsatile gonadorelin restored ovulation in 91% and 96% of patients respectively. This is strong human clinical-trial evidence for a narrowly defined indication.

[santoro-1990-mcc]

clinical

Indication specificity

Pulsatile GnRH was not useful in a small study of women with strictly defined polycystic ovarian disease, underscoring that the peptide treats hypothalamic GnRH deficiency rather than all anovulation syndromes.

[santoro-1990-mcc]

clinical

Reported side effects

IV line complications
clinical
In the hypothalamic amenorrhea trial, complications related to IV line placement ranged from 0% to 11% across sites, with a mean of 7%.
Multiple pregnancy and ovarian hyperstimulation
clinical
Multiple pregnancy occurred in 12% of treated patients in the same trial. One case of ovarian hyperstimulation occurred in a patient who had also received clomiphene.
Rare hypersensitivity / anaphylaxis
clinical
Rare but important hypersensitivity events are documented, including an IgE-mediated reaction and a pediatric anaphylaxis case after IV gonadorelin acetate.

Dosing notes

A clinical protocol for pulsatile SC gonadorelin used 10, 15, or 20 mcg per pulse at 90-minute intervals. Pharmacokinetic work in women with hypothalamic amenorrhea showed that 2.5, 5, and 10 mcg SC and 10 mcg IV boluses generated appropriate gonadotropin responses. The delivery pattern is at least as important as the amount: hypothalamic amenorrhea is a rational use case, classic PCOS is not.

Research use only. Information on this page is editorial reference, not medical or dosing advice. Always consult qualified medical guidance before use.

Storage

No consistent product-specific storage recommendation was identified across the retrieved therapeutic papers and protocols. Storage is highly formulation-dependent, and investigators should rely on the exact product label or trial pharmacy instructions rather than a generic peptide rule.

Vendors carrying Gonadorelin

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Discussion

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References

[santoro-1990-mcc]
Multicenter trial of pulsatile gonadorelin in hypothalamic amenorrhea
Santoro N et al. · 1990 · PubMed
Source
[gnrh-receptor-signaling]
GnRH receptor signaling: Gq/11, PLC, IP3/DAG, Ca2+, PKC
Review · PubMed (review)
Source
[hurley-1987-jcem]
Subcutaneous gonadorelin pharmacokinetics and pulse spacing
Hurley DM et al. · 1987 · Journal of Clinical Endocrinology & Metabolism
Source
[fda-gonadorelin-acetate]
Gonadorelin acetate substance record
FDA precisionFDA / GSRS · FDA precisionFDA GSRS
Source

Reported benefits

Restored ovulation in hypothalamic amenorrhea

Indication specificity

IV line complications

Multiple pregnancy and ovarian hyperstimulation

Rare hypersensitivity / anaphylaxis

Discussion