Leuprolide (Lupron) is an FDA-approved synthetic nonapeptide analog of gonadotropin-releasing hormone (GnRH), one of the most widely prescribed GnRH agonists.
Structure
9-residue peptide with D-leucine substitution at position 6, extending half-life from 3-4 minutes to ~3 hours.
Sequence: pGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt
Mechanism of Action
Paradoxical Effect
Initial Phase (1-2 weeks):
- Stimulates pituitary GnRH receptors
- Increases LH and FSH (transient "flare")
Continuous Administration (2-4 weeks+):
- GnRH receptor downregulation
- Dramatic reduction in LH, FSH
- Chemical castration (sex hormone suppression)
FDA-Approved Indications
- Prostate Cancer: First approved 1985
- Endometriosis: 6-month maximum use
- Uterine Fibroids
- Central Precocious Puberty
- IVF Protocols
Formulations
| Product | Dose | Duration |
|---|---|---|
| Lupron Depot | 7.5mg | 1 month |
| Lupron Depot | 22.5mg | 3 months |
| Lupron Depot | 30mg | 4 months |
| Lupron Depot | 45mg | 6 months |
Safety
FDA warnings (2010-2013): increased risk of diabetes, CV events, bone loss, thromboembolism. Hot flashes common.