Leuprorelin
Synthetic GnRH agonist — depot formulations FDA-approved for prostate cancer, endometriosis, central precocious puberty, and uterine fibroids.
🔬 Mechanism of Action
Leuprorelin (leuprolide) is a synthetic GnRH superagonist — it binds pituitary GnRH receptors with greater affinity and duration than endogenous GnRH. Initial administration causes a paradoxical "flare" with transient increases in LH, FSH, and gonadal steroids (testosterone/estrogen) lasting 1-2 weeks. Continuous exposure then desensitizes and downregulates GnRH receptors, producing chemical castration: LH/FSH suppression to castrate levels within 2-4 weeks, with testosterone dropping to <50 ng/dL in men. Depot formulations (microsphere or in-situ gel) provide sustained release over 1-6 months.
Source: PMID: 8613886
📜Background & History
Leuprorelin (leuprolide acetate) is one of the most prescribed GnRH agonists worldwide. Originally developed for prostate cancer, its ability to suppress gonadal steroids has expanded applications to endometriosis, uterine fibroids, central precocious puberty, and assisted reproduction. Depot formulations (Lupron Depot, Eligard) allow monthly, quarterly, or biannual administration.
🎯 Research Use Cases
- ✓Advanced prostate cancer
- ✓Endometriosis
- ✓Central precocious puberty
- ✓Uterine fibroids
- ✓Assisted reproduction
💉 Dosing Protocol
| Typical Dose | 3.75-22.5 mg depot (monthly-quarterly) |
| Frequency | Monthly or every 3-6 months (depot) |
| Half-Life | 3 hours |
⚠️Safety & Considerations
Initial flare can worsen symptoms in prostate cancer (bone pain, urinary obstruction) — co-administer an antiandrogen for first 2-4 weeks. Hot flashes, loss of bone density, and metabolic syndrome are common with prolonged use. Monitor bone density annually.
⚡Interactions & Contraindications
Anti-androgens co-administered during first 2-4 weeks to prevent flare. May reduce efficacy of some antidiabetic agents due to metabolic changes. Monitor bone density with prolonged use.
🔗Synergies & Common Stacks
Leuprorelin is a synthetic super-agonist of endogenous GnRH (gonadorelin). They share the same receptor but leuprorelin produces sustained downregulation rather than pulsatile stimulation.