From the FDA Drug Label
After oral administration of progesterone as a micronized soft-gelatin capsule formulation, maximum serum concentrations were attained within 3 hours. Tmax (hr) 1.5 ± 0.8 2.3 ± 1.4 1.7 ± 0. 6
The peak concentration of oral progesterone is reached within 3 hours after administration, with the time to maximum serum concentration (Tmax) ranging from 1.5 to 2.3 hours 1.
From the Research
Oral progesterone typically reaches its peak concentration in the bloodstream approximately 1-4 hours after ingestion, with most studies showing maximum levels around 2-3 hours post-administration. This timing varies based on the specific formulation used, with micronized progesterone being absorbed more rapidly than non-micronized forms 2. The formulation of oral progesterone, such as micronized progesterone in oil, can significantly impact the peak concentration and time to reach peak levels, with mean peak progesterone levels achieved at 2.0 +/- 0.3 hours after administration 2.
Factors Affecting Absorption
- Food intake significantly affects absorption, with high-fat meals enhancing bioavailability by up to 3-4 times compared to fasting conditions.
- The specific formulation of oral progesterone, such as micronized progesterone, can impact the rate and extent of absorption.
Clinical Implications
- The relatively short half-life of oral progesterone (approximately 5-20 hours) means that divided daily dosing is sometimes necessary for maintaining therapeutic levels throughout the day, especially when used for conditions requiring sustained progesterone effects such as luteal phase support or hormone replacement therapy 3.
- The rapid metabolism of oral progesterone in the liver results in lower bioavailability compared to other administration routes like vaginal or intramuscular formulations 4.
- Oral progesterone may be a clinically effective and well-tolerated alternative to synthetic progestins, with improvements in climacteric symptoms and quality of life 3.
Key Considerations
- The conversion of progesterone into a potent mineralocorticoid, such as deoxycorticosterone, may be a potential disadvantage of oral progesterone therapy 5.
- The effects of progesterone on central and peripheral allopregnanolone and beta-endorphin levels may be relevant to its therapeutic effects and potential side effects 6.