Lupron (Leuprolide) Usage and Dosing
Primary Clinical Applications
Leuprolide is a GnRH agonist with established dosing regimens that vary significantly by indication, ranging from 1 mg daily subcutaneous injections to depot formulations of 3.75-30 mg administered monthly to every 4 months. 1, 2
Prostate Cancer (Most Common Indication)
- Standard depot dosing: 7.5 mg IM monthly OR 22.5 mg IM every 3 months OR 30 mg IM every 4 months 3, 4
- Achieves castrate testosterone levels (≤50 ng/dL) within 2-4 weeks in 96% of patients 4
- The 30 mg depot formulation maintains castrate levels throughout 16-week intervals and demonstrates 80% favorable response rates 4
- Daily subcutaneous option: 1 mg (0.2 mL) daily, with injection site rotation 1
Breast Cancer (Premenopausal Hormone Receptor-Positive)
- Recommended regimen: Leuprolide 3.75 mg IM monthly OR 11.25-22.5 mg IM every 12 weeks, combined with aromatase inhibitor 3, 5
- Both monthly and 3-month depot formulations achieve equivalent ovarian ablation (estradiol <40 pg/mL) in 99-100% of patients 5
- Duration: 5 years optimal based on SOFT/TEXT trials, with minimum 2 years recommended 3
- Must initiate at least 1-2 cycles before starting aromatase inhibitor to ensure adequate estradiol suppression 3
Lupus Nephritis (Fertility Preservation During Cyclophosphamide)
- Indication: Women desiring future childbearing who require IV cyclophosphamide 3
- Dosing must be timed in relation to cyclophosphamide exposure 3
- Alternative consideration: Mycophenolate mofetil is now preferred for fertility preservation, as it avoids cyclophosphamide-related gonadotoxicity entirely 3
- Leuprolide use with oral cyclophosphamide is limited due to dosing coordination challenges 3
Endometriosis
- Standard regimen: 3.75 mg IM depot monthly for maximum 6 months 2
- Comparable efficacy to danazol 800 mg/day or buserelin 900 mcg/day 2
- Critical limitation: Duration restricted to 6 months due to bone mineral density reduction 2
Central Precocious Puberty
- Dosing range: 3.75-15 mg IM/SC depot monthly, adjusted by weight and response 2
- Decreases growth velocity and sexual maturation signs while increasing predicted adult height 2
Mechanism and Pharmacodynamics
- Initial effect: Transient gonadotropin surge during first week 1, 2
- Sustained effect: Pituitary desensitization/down-regulation leading to suppressed LH, FSH, and sex hormones 1, 2
- Testosterone levels typically increase above baseline in first week, then decline to castrate levels by weeks 2-4 1
Critical Monitoring Requirements
Breast Cancer Ovarian Suppression
- Essential monitoring: Estradiol and FSH/LH levels in patients <60 years who are amenorrheic ≤12 months 3
- Monitor prior to next GnRH agonist dose, particularly in women <45 years 3
- Warning: Aromatase inhibitors can stimulate ovarian function; vaginal bleeding requires immediate physician contact 3
Prostate Cancer
- Monitor serum testosterone biweekly or weekly for first 32 weeks to confirm castrate levels 4
- Assess PSA and prostatic acid phosphatase for treatment response 4
Pregnancy and Fertility Considerations
Leuprolide is contraindicated in pregnancy (may cause fetal harm) and should be discontinued during breastfeeding. 1
- Mechanism of harm: Animal studies show major fetal malformations at doses 1/600 to 1/6 human dose 1
- Male fertility: May impair fertility in males of reproductive potential; sperm banking recommended before treatment 3, 1
- Female fertility: Causes reversible suppression of reproductive function 1
Common Adverse Effects
- Most frequent: Hot flashes (45%), back pain (16%), arthralgia (14%) 4
- Musculoskeletal pain, fatigue, and insomnia common in breast cancer patients 5
- Rare but serious: Hypersensitivity vasculitis/serum sickness (case reports) 6
Administration Technique
- Inspect solution for discoloration and particulate matter before each injection 1
- Rotate injection sites with chronic subcutaneous administration 1
- Depot formulations: deep IM injection 3, 4