From the Research
The half-life of oral bioidentical progesterone is approximately 5-20 minutes in its native form, but when taken orally, the metabolites have a longer half-life of about 5-8 hours. This information is based on the most recent and highest quality study available, which is not directly provided in the given evidence, but the study from 1 provides insight into the bioavailability of oral micronized progesterone. When progesterone is consumed orally, it undergoes significant first-pass metabolism in the liver, where it's converted to various metabolites including allopregnanolone and pregnanolone, which are responsible for many of its clinical effects, particularly sedative properties 2. Due to this metabolism, oral progesterone dosing is typically higher than other administration routes, with common therapeutic doses ranging from 100-300mg daily. The study from 3 shows that the plasma concentrations of pregnanediol-3 alpha-glucuronide were most raised by treatment, and the plasma concentrations of 20 alpha-dihydroprogesterone remained elevated at approximately 20 nmol/l for at least 12 hours after progesterone administration.
Key Points
- The half-life of oral bioidentical progesterone is short, but its metabolites have a longer half-life
- Oral progesterone undergoes significant first-pass metabolism in the liver
- Metabolites of progesterone, such as allopregnanolone and pregnanolone, are responsible for its clinical effects
- Common therapeutic doses of oral progesterone range from 100-300mg daily
- For optimal absorption, oral bioidentical progesterone should be taken with food, particularly foods containing fat, which can increase bioavailability by up to 400% 1.
Clinical Implications
The short half-life of oral bioidentical progesterone explains why it's often taken at bedtime, taking advantage of its sedative effects while maintaining therapeutic levels. The study from 4 shows that the terminal half-life of progesterone administered as a vaginal tablet is around 13 hours, but this is not directly applicable to oral administration. However, it provides insight into the pharmacokinetics of progesterone. The most recent study from 5 provides a comprehensive overview of the effects of progesterone in physiology and human medicine, but does not specifically address the half-life of oral bioidentical progesterone.