Pharmacokinetics of progesterone and its metabolites allopregnanolone and pregnanolone after oral administration of low-dose progesterone.
Level 4 - case-series / case-control
Uncontrolled single-arm pharmacokinetic study
PubMed 16406399 · doi:10.1016/j.maturitas.2005.11.005
What was done
Eight postmenopausal women were administered a single oral dose of 20 mg of micronised progesterone on Day 1 and 20 mg twice daily on Days 2-7. Blood samples were collected to measure progesterone, allopregnanolone, and pregnanolone plasma concentrations and calculate pharmacokinetic parameters.
What was found
After a single dose, AUC (0-12 h) was 127% higher for progesterone, 196% higher for allopregnanolone, and 119% higher for pregnanolone compared to estimated endogenous baseline production. Cmax and AUC were significantly lower for pregnanolone than for progesterone and allopregnanolone. Steady-state trough concentrations (Css) were significantly higher than baseline for all measured compounds, and allopregnanolone Css reached levels normally seen during the menstrual cycle. Absolute concentrations and measures of variance were not reported in the abstract.
Why it matters
This study demonstrates that low-dose oral progesterone produces allopregnanolone concentrations comparable to physiological premenopausal levels, indicating it can serve as an oral prodrug to study allopregnanolone effects in humans.
Limits
The study is limited by a very small sample size (n = 8) and an uncontrolled, single-arm design. Absolute pharmacokinetic values, confidence intervals, and clinical or physiological efficacy outcomes were not reported in the abstract.
Cited by
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