Progesterone clearance after oral, vaginal, or intramuscular administration
Progesterone is metabolized extensively in the liver to pregnanediols and pregnanolones that are then conjugated and eliminated via renal and biliary routes. [1]
Clearance time depends mainly on the route-specific absorption profile and the elimination half-life of systemic progesterone. [1]
Oral micronized progesterone (capsules)
After oral administration of micronized progesterone, the serum elimination half-life is reported as 13 to 17 hours. [2]
Most systemic progesterone is eliminated within about 3 to 4 days after the last dose when clearance is estimated as ~5 elimination half-lives (65 to 85 hours). [2]
Vaginal progesterone (gel; eg, Crinone)
For vaginal progesterone gel (Crinone), progesterone absorption is prolonged with an absorption half-life of about 25 to 50 hours. [3]
For Crinone, systemic elimination of progesterone has an elimination half-life of about 5 to 20 minutes. [3]
Because pharmacokinetics are rate-limited by absorption rather than elimination for Crinone, systemic levels after stopping dosing are expected to decline over several days rather than minutes. [3]
Vaginal progesterone (insert/capsule)
For vaginal inserts, systemic progesterone is absorbed to measurable serum concentrations and steady-state concentrations are reported to be achieved within about 1 day after initiation in studies of progesterone vaginal insert. [4]
The specific elimination half-life for vaginal insert formulations is not provided in the referenced insert labeling excerpt. [4]
Intramuscular progesterone in oil
After intramuscular administration of progesterone in oil (10 mg), maximum plasma concentrations are reached within about 8 hours and plasma concentrations remain above baseline for about 24 hours. [5]
Based on the labeled absorption/above-baseline duration, systemic progesterone is expected to fall substantially within roughly 1 to 2 days after the last intramuscular injection of progesterone in oil. [5]
Key determinants of “cleared from the body”
Progesterone clearance is driven by hepatic metabolism followed by renal and biliary elimination of metabolites. [1]
Route-specific absorption (especially prolonged absorption after some vaginal formulations) determines how long measurable systemic progesterone persists after discontinuation. [3]
Practical timing estimates (systemic progesterone)
- Oral micronized progesterone: typically several days (~3 to 4 days) to be largely eliminated after the last dose. [2]
- Vaginal progesterone gel (Crinone): elimination is rapid, but systemic levels can persist for several days due to prolonged absorption. [3]
- Intramuscular progesterone in oil: systemic concentrations are above baseline for about 24 hours after a 10 mg dose, suggesting substantial decline within about 1 to 2 days after the last injection. [5]
Sources
These estimates are based on elimination half-life and labeled above-baseline/absorption half-life parameters for specific progesterone formulations. [2] [3] [5]