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.
Sexual & Hormonal
Leuprolide
A long-acting GnRH agonist that suppresses sex hormone production by overstimulating the pituitary. Approved for prostate cancer, endometriosis, fibroids and precocious puberty.
Overview
Leuprolide is GnRH modified to last, and that change flips its effect. Instead of the natural pulse, the pituitary gets continuous stimulation. For the first week or two it responds by releasing more LH and testosterone — the "flare" — and then it downregulates its receptors and effectively switches off. Testosterone or oestrogen falls to castrate levels and stays there while treatment continues.
A nonapeptide GnRH agonist with D-Leu at position 6 and ethylamide replacing Gly10, conferring roughly 15-fold greater receptor affinity and resistance to degradation. Continuous receptor occupancy causes gonadotroph desensitisation and GnRH receptor downregulation within 2–4 weeks, suppressing LH and FSH and producing medical castration. The initial flare requires antiandrogen cover in metastatic prostate cancer to prevent symptomatic tumour stimulation. Formulated as 1-, 3-, 4- and 6-month intramuscular or subcutaneous depots using polymer microsphere or in-situ gel delivery.
Research areas
Prostate cancerEndometriosisPrecocious pubertyUterine fibroids
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 |
|---|---|
| 7.5 mg intramuscularly every month, or 22.5 mg every 3 months, in advanced prostate cancerAn antiandrogen is usually given for the first weeks to cover the testosterone flare. | Approved product labelling |
| 3.75 mg intramuscularly monthly for up to 6 months in endometriosis, with hormonal add-back | Approved product labelling |
Trial status
Approved since 1985 with an extensive completed trial record across indications.
Reported safety signals
- The initial testosterone flare can worsen symptoms in metastatic prostate cancer, including spinal cord compression — antiandrogen cover is standard.
- Bone mineral density falls with prolonged hypogonadism; monitoring and add-back therapy are used to manage this.
- Hot flushes, sexual dysfunction, mood change and metabolic effects are expected consequences of hormone suppression.
- Cardiovascular risk with androgen deprivation therapy has been a subject of ongoing study.
Common questions
What is the "flare" and why does it matter?
For the first one to two weeks, continuous GnRH stimulation raises LH and testosterone before the pituitary shuts down. In metastatic prostate cancer that surge can transiently worsen the disease, which is why an antiandrogen is started before or alongside the first depot.
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.
How this profile was built →