Leuprolide
A long-acting GnRH agonist that suppresses sex hormone production by overstimulating the pituitary. Approved for prostate cancer, endometriosis, fibroids and precocious puberty.
Sexual & Hormonal
Gonadorelin
The natural GnRH decapeptide. Its very short half-life means it must be pulsed, which is precisely what distinguishes it from the agonists used to shut the axis down.
Overview
The hypothalamus releases GnRH in pulses roughly every 60 to 120 minutes, and the pituitary responds by releasing LH and FSH, which drive the gonads. The pulsing is essential: continuous GnRH exposure does the opposite and shuts the pituitary down within about two weeks. Gonadorelin is the natural hormone, so given as a pulse it stimulates. That is why it is used in pump form to restore fertility in hypothalamic hypogonadism, and as a single injection to test pituitary function.
The native GnRH decapeptide (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) with a plasma half-life of 2–4 minutes. Pulsatile GnRH receptor stimulation on pituitary gonadotrophs maintains receptor expression and Gq/PLC signalling, driving LH and FSH release. Continuous exposure produces receptor downregulation and desensitisation after an initial flare — the pharmacological basis of leuprolide and the other GnRH agonists. Pulsatile subcutaneous or intravenous administration by pump every 60–120 minutes restores ovulation in hypothalamic amenorrhoea and spermatogenesis in idiopathic hypogonadotropic hypogonadism.
Research areas
Hypogonadotropic hypogonadismFertility inductionPituitary function testing
Dosing reported in the literature
Every protocol below is reproduced from a published study or approved labelling, with its source named. These are records of what was studied — not recommendations, and not a suggestion that any of them is appropriate for any person.
| Protocol as reported | Source |
|---|---|
| 5–20 mcg subcutaneously or intravenously every 90 minutes by portable pump for ovulation induction | Pulsatile GnRH fertility protocols |
| 100 mcg intravenously with LH and FSH measured over 2 hours as a pituitary stimulation test | GnRH stimulation test protocol |
Trial status
Established clinical use in hypothalamic hypogonadism and pituitary function testing.
Reported safety signals
- Multiple pregnancy risk exists with ovulation induction, though it is lower than with gonadotropin injections.
- Requires an indwelling pump for fertility use, with the associated infection and site risks.
- Hypersensitivity reactions have been reported, including rare anaphylaxis with repeated use.
- Continuous rather than pulsatile administration will suppress rather than stimulate the axis — the delivery pattern is not optional.
Common questions
How can the same hormone both stimulate and suppress the reproductive axis?
Pulses maintain receptor expression on the pituitary; continuous exposure downregulates it. Gonadorelin given every 90 minutes stimulates. Leuprolide, which is the same signal made long-lasting, suppresses. It is the clearest example in endocrinology of a signal's pattern mattering more than its presence.
Primary sources
Medical disclaimer
This page is for informational and research purposes only. Nothing here constitutes medical advice. The compounds discussed are research chemicals. Consult a qualified clinician before starting any protocol.
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