Leuprolide (leuprorelin) is a synthetic GnRH (gonadotropin-releasing hormone) agonist nonapeptide (MW ~1209.4 g/mol) that is one of the most widely prescribed hormonal therapies in oncology and reproductive medicine. It is FDA-approved for advanced prostate cancer, endometriosis, uterine fibroids, central precocious puberty, and as part of assisted reproductive technology protocols. Available as depot injections (monthly, 3-month, 4-month, 6-month) and subcutaneous implants, leuprolide provides sustained GnRH receptor stimulation leading to desensitization and profound suppression of gonadotropins and sex steroids.
Category: Reproductive / Hormonal. Evidence rating: A (strong human clinical data).
Clinical status: FDA-approved (Lupron Depot for prostate cancer, endometriosis, uterine fibroids, central precocious puberty; Eligard for prostate cancer; Fensolvi for central precocious puberty)
Leuprolide is a GnRH agonist approximately 15-100 times more potent than native GnRH. It operates through a "flare then suppression" mechanism: initial administration causes a transient stimulation ("flare") of pituitary gonadotropin release (LH and FSH surge), leading to a temporary increase in…
Safety considerations: Hot flashes/vasomotor symptoms (most common, up to 55-80% of patients); Bone mineral density loss with prolonged use (limit treatment to 6 months for endometriosis without add-back therapy); Initial testosterone/estrogen flare during first 1-2 weeks: may worsen bone pain or urinary symptoms in prostate cancer (can be prevented by concurrent anti-androgen).
Reviewed by the PeptideAtlas Editorial Team.
| Amino-acid sequence | pGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt |
|---|---|
| Molecular weight | ~1209.4 g/mol |
| CAS number | 53714-56-0 |
| Half-life | ~3 hours (subcutaneous); effective duration 1-6 months (depot formulations) |
| Production method | synthetic |
| Anti-doping status | Prohibited in sport (WADA) |
| US regulatory status | FDA-approved. Lupron Depot (1-month, 3-month, 4-month, 6-month depot): prostate cancer, endometriosis, uterine fibroids, CPP. Eligard (1-month, 3-month, 4-month, 6-month): prostate cancer. Fensolvi (6-month): CPP. |
Related peptides: Kisspeptin, Gonadorelin, Oxytocin.
Compare: Leuprolide vs Gonadorelin.
Leuprolide is a GnRH agonist that initially stimulates pituitary GnRH receptors, causing a surge of LH and FSH release and a temporary rise in testosterone. With continued daily receptor stimulation, the pituitary GnRH receptors become desensitized and downregulated, leading to profound suppression of gonadotropins and testosterone within 2-4 weeks. The initial flare can be blunted by starting…
FDA labeling limits initial treatment to 6 months, with retreatment for another 6 months permitted if used with add-back therapy (norethindrone acetate 5 mg daily). Prolonged use without add-back is limited by bone mineral density loss, typically not exceeding 1-2% per 6-month course, which is partially reversible.
Both contain leuprolide acetate but use different sustained-release technologies. Lupron Depot uses PLGA microspheres reconstituted with diluent for IM injection. Eligard uses the Atrigel delivery system (PLGA dissolved in a biocompatible solvent) that forms a solid depot after subcutaneous injection. Both achieve comparable testosterone suppression.
Leuprolide is used off-label to suppress puberty in transgender and gender-diverse adolescents, providing time for gender identity assessment before irreversible pubertal changes. This use follows Endocrine Society guidelines but remains a subject of ongoing medical and policy discussion.
Coverage on this site: Tag-Assisted Peptide Synthesis: How TAPS Works and Its Benefits, FDA Peptide Vote Health Question, Leuprolide Acetate's Key Role in Reproductive Disorders.