What is the recommended dose of leuprolide (GnRH agonist) for a 3-month regimen?

Leuprolide 3-Month Depot Dosing for Ovarian Suppression

For a 3-month leuprolide depot regimen in premenopausal women requiring ovarian suppression (such as for fertility preservation during cyclophosphamide therapy or adjuvant endocrine therapy for breast cancer), administer 11.25 mg intramuscularly every 3 months. 1

Dosing Rationale

• The 11.25 mg dose every 3 months is the standard formulation recommended by the American College of Rheumatology for ovarian suppression in women receiving cyclophosphamide therapy for rheumatic and musculoskeletal diseases. 1

• This dosing achieves adequate gonadotropin suppression and ovarian protection comparable to monthly administration schedules. 2

• The 2020 ACR guideline specifically addresses GnRH agonist co-therapy (typically leuprolide acetate) for ovarian protection during monthly intravenous cyclophosphamide, with monthly administration being the studied regimen. 1

Clinical Context and Timing

• Optimal timing is 10-14 days prior to the first cyclophosphamide dose, though logistical challenges may prevent this in urgent situations. 1

• For breast cancer patients requiring ovarian suppression with aromatase inhibitors, the 22.5 mg every 3 months formulation has also demonstrated equivalent efficacy to monthly 7.5 mg dosing, with 99-100% achieving ovarian ablation (estradiol <40 pg/mL and FSH 23-116 mU/mL). 2

Alternative Dosing Considerations

• The 22.5 mg every 3 months dose may be considered if more robust suppression is desired, particularly in patients where ensuring complete ovarian suppression is critical. 2

• Research in breast cancer patients showed that 22.5 mg every 3 months achieved ovarian ablation in 99% of patients compared to 100% with monthly dosing, with comparable disease-free survival (97% vs 95% at 1 year). 2

• However, 11.25 mg remains the guideline-recommended dose for fertility preservation contexts based on the ACR recommendations. 1

Important Caveats

• Cessation of menses alone does not confirm adequate ovarian suppression. 1

• Patients should be monitored for signs of incomplete suppression, including resumption of menses or cyclical climacteric symptoms. 1

• While routine estradiol monitoring was not used in clinical trials to alter care, finding premenopausal estradiol levels indicates incomplete suppression. 1

• The Euro-Lupus cyclophosphamide regimen (lower cumulative dose) may theoretically not require GnRH agonist co-therapy, though this remains uncertain. 1

Administration Details

• Duration: 5 years when used for adjuvant endocrine therapy in breast cancer. 1

• Route: Intramuscular injection every 3 months. 1, 2

• Most common adverse effects include hot flashes, musculoskeletal pain, fatigue, and insomnia, which are comparable between monthly and 3-monthly formulations. 2