Medroxyprogesterone Acetate Half-Life
The half-life of medroxyprogesterone acetate (MPA) is approximately 50 days for intramuscular depot injection (DMPA-IM), with MPA detectable in serum for 120-200 days after a single 150 mg injection. 1
Intramuscular Depot Formulation (DMPA-IM)
The FDA-approved prescribing information provides the most definitive pharmacokinetic data for depot medroxyprogesterone acetate:
- Apparent half-life: approximately 50 days following intramuscular administration of 150 mg DMPA-IM 1
- Peak concentrations: 1-7 ng/mL, reached approximately 3 weeks after injection 1
- Duration of detection: MPA becomes undetectable (<100 pg/mL) between 120-200 days following a single injection 1
- Pharmacokinetic profile: Concentrations increase for approximately 3 weeks, then decrease exponentially 1
The prolonged half-life explains why DMPA is administered every 3 months (13 weeks) for contraceptive efficacy, with a 2-week grace period (up to 15 weeks from last injection) without requiring additional contraceptive protection 2
Subcutaneous Depot Formulation (DMPA-SC)
The subcutaneous formulation has similar pharmacokinetic properties to the intramuscular formulation:
- Dosing interval: Every 3 months (13 weeks), identical to DMPA-IM 2
- Recommendations for initiation, follow-up, and reinjection intervals are the same for both DMPA-SC and DMPA-IM 2
- Comparative studies demonstrate similar efficacy and pharmacodynamic parameters between SC and IM routes 3
Oral Medroxyprogesterone Acetate
The oral formulation has dramatically different pharmacokinetics compared to depot formulations:
- Half-life: 4-7 hours after intravenous injection in research studies 4
- This short half-life necessitates daily oral dosing, in stark contrast to the quarterly depot injections
- The major metabolite following administration is a glucuronide conjugate 4
Clinical Implications
Return to fertility is delayed for several months after discontinuing DMPA because ovulation resumes only when MPA levels fall below 0.1 ng/mL 5. Women with lower body weights conceive sooner than women with higher body weights after discontinuation 1.
The prolonged half-life of depot formulations creates a sustained contraceptive effect through multiple mechanisms: inhibition of gonadotropin secretion, prevention of follicular maturation and ovulation, and endometrial thinning 1, 5.
Important Caveats
- Drug-drug interactions with CYP3A4 inducers (efavirenz, rifampicin) can increase MPA clearance by 24.7-52.4%, potentially requiring more frequent dosing every 8-10 weeks instead of 12 weeks 6
- Conversely, protease inhibitors like lopinavir/ritonavir decrease clearance by 28.7% but may shorten terminal half-life 6
- The effect of hepatic or renal disease on DMPA pharmacokinetics is unknown 1