Leuprolide

Summary

Leuprolide (leuprorelin) is a GnRH agonist used for the treatment of hormone-sensitive prostate cancer, endometriosis, uterine fibroids, central precocious puberty, and as part of assisted reproduction protocols. After an initial flare in sex hormone levels, continuous use leads to a profound and reversible reduction in gonadal steroid production.

Mechanism of Action

Synthetic analogue of gonadotropin-releasing hormone (GnRH) that, upon continuous administration, causes downregulation and desensitization of pituitary GnRH receptors, leading to suppression of LH and FSH secretion, and subsequent reduction of gonadal sex steroid production (testosterone in males, estrogen in females).

Routes of Administration

Goals & Uses

• Central precocious puberty (CPP)Pediatric EndocrinologyHigh
• Prostate cancer (hormone-sensitive, advanced)OncologyHigh
• Uterine fibroids (leiomyomata)GynecologyHigh
• Assisted reproduction (controlled ovarian stimulation)Reproductive MedicineModerate
• Gender-affirming hormone therapy (puberty suppression)EndocrinologyModerate
• EndometriosisGynecologyHigh

Contraindications

• Undiagnosed vaginal bleedingGynecologicalHigh
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• BreastfeedingPopulationHighPotential transfer into breast milk or insufficient safety data
• Hypersensitivity to GnRH analogues or excipientsImmunologicHigh
• Spinal cord compression risk (prostate cancer)OncologyHigh

Adverse Effects

• Hot flashes / vasomotor symptomsAutonomic / ThermoregulatoryCommon
• Testosterone/estrogen flare (initial)EndocrineCommon
• Injection site reactionsLocalCommon
• Sexual dysfunction (decreased libido, erectile dysfunction)Sexual HealthCommon
• Bone mineral density loss / osteoporosisMusculoskeletalCommon
• QT/QTc prolongationCardiovascularUncommon

Drug Interactions

• Antidiabetic agents (insulin, sulfonylureas)Moderate
• QT-prolonging agents (e.g., antiarrhythmics, antipsychotics)High
• Anticoagulants (warfarin)Moderate

Population Constraints

• Pediatric patients (outside CPP indication)AgeRelative
• Patients with osteoporosis or high fracture riskMusculoskeletalRelative
• Patients with pre-existing cardiovascular diseaseCardiovascularRelative
• Patients with depression or psychiatric disordersPsychiatricRelative

Regulatory Status

• European UnionApprovedApproved: Prostate cancer, Endometriosis, Uterine fibroids, Central precocious puberty, Female infertility (IVF)Approved under various brand names (Prostap, Lucrin, Enantone) across EU member states via national procedures.
• United StatesApprovedApproved: Advanced prostate cancer, Endometriosis, Uterine leiomyomata (fibroids), Central precocious pubertyFDA approved since 1985; multiple brand names and formulations (Lupron, Lupron Depot, Eligard, Viadur) approved; Viadur implant discontinued commercially but approved.
• United KingdomApprovedApproved: Prostate cancer, Endometriosis, Uterine fibroids, Central precocious pubertyApproved by MHRA; available as Prostap SR and Prostap 3 DCS; included in NICE guidance for relevant oncology and gynecological indications.

Approved by FDA in 1985 (Lupron). Multiple formulations approved including daily injections, monthly and 3/4/6-month depot preparations, and a subcutaneous implant (Viadur). Included on WHO Essential Medicines List for specific indications.

Evidence & Sources

No sources recorded yet.