Leuprolide (Lupron) - GnRH Agonist for Androgen Deprivation Therapy — Reproduction
FDA-approved GnRH agonist for advanced prostate cancer, endometriosis, uterine fibroids, and precocious puberty via testosterone/estrogen suppression.
Overview
Leuprolide acetate (Lupron) is a synthetic gonadotropin-releasing hormone (GnRH) agonist FDA-approved for advanced prostate cancer (androgen deprivation therapy), endometriosis, uterine fibroids, and central precocious puberty. Paradoxical mechanism: initial GnRH receptor stimulation causes brief testosterone/estrogen surge, followed by receptor downregulation and sustained suppression of LH/FSH secretion. Phase 3 trials show 99.4% achieve castrate testosterone levels (≤50 ng/dL) by day 28, with 94% maintaining ≤20 ng/dL throughout treatment. Available in 1-month, 3-month, 4-month, and 6-month depot formulations for convenience. In men, induces medical castration for prostate cancer. In women, suppresses estrogen for endometriosis/fibroids. Standard first-line hormonal therapy for advanced/metastatic prostate cancer.
Indications
- Advanced prostate cancer (palliative androgen deprivation therapy)
- Endometriosis (pre-surgical or symptom management)
- Uterine leiomyomata (fibroids) - pre-operative shrinkage
- Central precocious puberty (children)
- Gender-affirming hormone therapy (off-label, feminizing regimens)
Mechanism of Action
Prostate cancer: testosterone-dependent growth. Endometriosis/fibroids: estrogen-dependent
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Leuprolide acetate 7.5 mg depot | 7.5 mg IM | Every 4 weeks (monthly) | Add bicalutamide 50 mg PO daily for first 4 weeks to prevent testosterone flare |
| Leuprolide acetate 22.5 mg depot | 22.5 mg SC or IM | Every 12 weeks (quarterly) | Equivalent efficacy to monthly; reduces injection frequency; add antiandrogen for first dose |
| Leuprolide acetate 45 mg depot | 45 mg SC | Every 24 weeks (semi-annually) | Only 2 injections/year; 93.4% achieve testosterone ≤50 ng/dL from week 4-48 |
| Leuprolide acetate 3.75 mg depot | 3.75 mg IM | Every 4 weeks | Maximum 6 months duration; add-back therapy (estrogen/progesterone) to reduce bone loss and hot flashes |
| Leuprolide acetate 11.25 mg depot | 11.25 mg IM | Every 12 weeks | Pre-operative shrinkage; maximum 3-6 months |
Evidence Grade
GRADE A
Safety & Contraindications
- ⚠️ PRESCRIPTION MEDICATION - Oncology/endocrinology supervision required
- TESTOSTERONE FLARE in first 2-3 weeks: Initial LH surge causes transient ↑testosterone (may worsen bone pain, urinary obstruction, spinal cord compression in prostate cancer) - add antiandrogen (bicalutamide) for first 4 weeks
- Cardiovascular risks: Increased risk of myocardial infarction, stroke, sudden cardiac death with long-term ADT - monitor cardiovascular risk factors
- Metabolic syndrome: Weight gain, insulin resistance, dyslipidemia, diabetes risk
- Bone loss: Significant osteoporosis risk with long-term use - DEXA screening, calcium/vitamin D, consider bisphosphonates
- Hot flashes (80%): Most common side effect; may use low-dose estrogen patch or venlafaxine
- Sexual dysfunction: Erectile dysfunction, loss of libido (expected effect)
- Depression, cognitive changes, fatigue: Common with long-term ADT
- In women: Menopausal symptoms, bone loss, mood changes
- NOT for pregnancy (Category X); use contraception during treatment