How long does the Lupron (Leuprolide) shot stay in the body?

Duration of Lupron (Leuprolide) in the Body

Lupron (leuprolide acetate) remains active in the body for 1-4 months depending on the specific depot formulation used, with drug effects persisting until the microspheres fully degrade and release all medication.

Pharmacokinetics of Leuprolide Depot Formulations

Leuprolide acetate is a synthetic gonadotropin-releasing hormone (GnRH) agonist that is administered as a depot injection. The duration of action varies based on the specific formulation:

• 1-month depot formulation: Uses polylactic/glycolic acid (PLGA) microspheres and maintains therapeutic plasma concentrations between 0.4-1.4 μg/L for approximately 28 days 1
• 3-month depot formulation: Uses polylactic acid (PLA) microspheres and maintains continuous drug concentrations from 0.43-0.19 μg/L from day 7 until before the next injection 1
• 4-month depot formulation: The 30 mg formulation maintains castrate levels of testosterone for 16 weeks (4 months) 2
• 12-month implant: Can deliver leuprolide continuously for up to 52 weeks with steady mean concentrations of 0.93 μg/L 1

Pharmacodynamic Effects and Duration

The pharmacodynamic effects of leuprolide (suppression of hormone production) follow a predictable pattern:

1. Initial phase: After injection, there is a transient increase in hormone levels (testosterone or estrogen) during the first 1-2 weeks
2. Suppression phase: Hormone levels decrease to castrate levels within 2-4 weeks after administration 3
3. Maintenance phase: Suppression is maintained for the duration of the depot formulation's activity
4. Recovery phase: After the drug effect wears off, normal hormone function typically returns within 4-12 weeks after treatment is discontinued 3

Clinical Considerations for Different Formulations

Monthly (3.75 mg or 7.5 mg) Depot

• Achieves castrate levels of testosterone within 3 weeks (median 22 days) 2
• Maintains suppression for approximately 4-5 weeks
• Used when more frequent dose adjustments may be needed

3-Month (11.25 mg or 22.5 mg) Depot

• Equally effective as monthly injections for hormone suppression 4
• More convenient dosing schedule
• Studies show 99% effectiveness in achieving ovarian ablation compared to 100% with monthly dosing 4

4-Month (30 mg) Depot

• Achieves castrate levels in 96% of patients within 4 weeks
• Maintains suppression for 16 weeks
• Even with a delay of injection by up to 3 weeks, testosterone suppression is maintained 2

Elimination and Clearance

• Leuprolide has a total body clearance of approximately 9.1 L/h after subcutaneous injection 1
• The elimination half-life of the immediate-release formulation is approximately 3 hours 3
• However, the depot formulations provide sustained release from the microspheres, extending the effective duration far beyond the elimination half-life of the drug itself

Important Considerations

• The effects of leuprolide may persist longer than the stated dosing interval
• When planning for pregnancy or discontinuing treatment, allow 4-12 weeks after the last injection for hormonal function to normalize 3
• For patients receiving immunosuppressive therapy, the timing of live vaccines should consider the duration of leuprolide's immunosuppressive effects 5

Special Populations

• No specific dose adjustments are required for hepatic or renal impairment, as pharmacokinetic studies in these populations are limited 3
• The drug's effects may be more prolonged in elderly patients due to age-related changes in metabolism

In summary, Lupron (leuprolide) remains active in the body according to its specific depot formulation (1,3,4, or 12 months), with hormonal effects typically persisting for the full duration of the intended dosing interval and hormonal recovery occurring within 1-3 months after the last injection.