Side by side
| A Leuprolide (leuprorelin) | B Gonadorelin (GnRH) | |
|---|---|---|
| LYO grade | A | B |
| Molecule | GnRH analogue with two substitutions; long-acting | Synthetic natural GnRH, 10 residues; half-life minutes |
| Effect on LH/FSH | Surge, then suppression to near zero | Pulsed: sustained release · Continuous: suppression |
| Licensed uses | Prostate cancer, endometriosis, fibroids, central precocious puberty, IVF protocols | Pituitary-function test; pulsatile pump for hypogonadotropic hypogonadism |
| Key evidence | 1984 NEJM trial: response 86% vs 85% on diethylstilbestrol with fewer serious side effects; decades of use | Meta-analysis of 420 men on pulsatile therapy: larger testes and earlier sperm than gonadotropin injections |
| 'Keep the testes working' on TRT | Not a use | No controlled trial found |
| Adverse effects | Hormone-deprivation effects: hot flushes, bone and muscle loss, cardiometabolic signal | Infusion-site allergy on pump therapy |
| Sport (WADA) | Prohibited for males (S2, named as leuprorelin) | Prohibited for males (S2) |
Different jobs, not rivals. Leuprolide is the drug for turning the axis off; gonadorelin by pump is the drug for turning it on in people whose own signal is missing. Neither is evidence for the TRT add-on use gonadorelin is sold for.
Why the same hormone does opposite things
The GnRH receptor responds to rhythm. The hypothalamus releases GnRH roughly every 60–120 minutes, and that pulse keeps the pituitary producing LH and FSH. Bathe the receptor continuously — with a depot injection of leuprolide, or with a natural hormone given too often — and it downregulates within one to three weeks, and gonadotropin output collapses. Leuprolide was built to exploit that; gonadorelin pumps are built to avoid it.
What the evidence supports
Leuprolide's evidence is forty years deep. The 1984 trial that launched it matched diethylstilbestrol on prostate-cancer response with far fewer cardiovascular and breast side effects, and the licensed indications have expanded on the same mechanism. Gonadorelin's evidence is narrower: a licensed single-dose pituitary test, and pulsatile pump therapy for men and women with hypogonadotropic hypogonadism, where a meta-analysis of 420 men found larger testes and earlier sperm than gonadotropin injections but no difference in the pregnancy rate.
The use gonadorelin is sold for
Clinics add gonadorelin to testosterone replacement to prevent testicular shrinkage, usually as two or three injections a week. That schedule is neither the natural pulse nor a true continuous infusion, and no controlled study has tested it for testicular size, fertility or hormone recovery. The rationale borrows from hCG, which does have data for that purpose. Leuprolide's pharmacology is a warning here: GnRH given the wrong way suppresses rather than stimulates.
Questions people actually ask
Can gonadorelin replace hCG on TRT?
Is leuprolide a form of chemical castration?
Are both banned in sport?
References
- 1
- 2