From the Guidelines
The half-life of oral progesterone is approximately 16-18 hours due to its micronized formulation, which undergoes extensive first-pass metabolism in the liver. This significant difference in half-life occurs because natural progesterone has a short half-life, but when taken orally in its micronized form, it is converted to various metabolites with longer half-lives, contributing to the overall duration of action 1. When considering the pharmacokinetics of oral progesterone, it's essential to note that its bioavailability can be increased by taking it with food, particularly a fatty meal, which can enhance its absorption by approximately 2-3 times compared to fasting conditions. Key points to consider when prescribing oral progesterone include:
- Typical dosing ranges from 100-200 mg daily or twice daily
- Higher doses are often used for specific conditions like luteal phase support or hormone replacement therapy
- The micronized formulation is designed to improve absorption and extend the therapeutic effect
- Taking progesterone with food or at bedtime can help manage its sedative side effects and improve bioavailability. In clinical practice, understanding the pharmacokinetics of oral progesterone, including its half-life and factors influencing its bioavailability, is crucial for effective treatment and minimizing side effects, as seen in studies like the one on preterm birth prevention, where oral progesterone was used as an adjunct to tocolysis 1.
From the Research
Half-Life of Oral Progesterone
The half-life of oral progesterone is not explicitly stated in the provided studies as a single, definitive value. However, we can look at the duration for which progesterone levels remain elevated after administration to infer its half-life.
- In the study 2, after a single dose of 100 mg, serum concentrations of progesterone were around 50-60 nM and elevated levels persisted for 8-12 hours.
- The study 3 found that after administering 200 mg of micronized progesterone, peak concentrations were reached at an average of 2.8 hours, and significant elevation of progesterone over baseline levels persisted for at least 6 hours after the single oral dose and returned to initial levels by 24 hours.
- The study 4 showed that mean peak progesterone levels were achieved with micronized progesterone in oil at 2.0 hours after administration, and significant serum progesterone levels were maintained for several hours, though the exact duration varied based on the formulation and vehicle used.
Factors Influencing Half-Life
The half-life and absorption of oral progesterone can be influenced by several factors, including:
- Vehicle: The use of oil or other vehicles can enhance absorption 4.
- Particle size: Micronization of progesterone can improve absorption 3, 4.
- Dosing regimen: The timing and amount of doses can affect peak levels and duration of action 5.
Pharmacokinetics
The pharmacokinetics of oral progesterone, including its absorption, distribution, metabolism, and excretion, play a crucial role in determining its half-life. Studies have shown that oral progesterone is rapidly absorbed, with peak levels reached within a few hours 5, 3, 4. However, the specific half-life value is not consistently reported across these studies.