Progesterone Dosing Regimen Recommendations
For prevention of endometrial hyperplasia in postmenopausal women with a uterus receiving estrogen therapy, progesterone should be administered as a single daily dose of 200 mg orally at bedtime for 12 days sequentially per 28-day cycle. 1
Dosing Regimens Based on Clinical Indication
Prevention of Endometrial Hyperplasia
- Dose: 200 mg oral progesterone daily
- Timing: At bedtime
- Duration: 12 days sequentially per 28-day cycle
- Patient population: Postmenopausal women with a uterus receiving daily conjugated estrogens 1
Treatment of Secondary Amenorrhea
- Dose: 400 mg oral progesterone daily
- Timing: At bedtime
- Duration: 10 days
- Administration tip: Take with a glass of water while standing if swallowing difficulties occur 1
Hormone Replacement Therapy Options
For postmenopausal women requiring hormone replacement therapy, several regimens are available:
- Cyclic regimen with regular bleeding: 300 mg/day at bedtime for 10 days per month 2
- Cyclic regimen with less bleeding: 200 mg/day for 14 days per month 2
- Continuous regimen for amenorrhea: 100 mg/day for 25 days per month 2
Evidence for Efficacy and Safety
Oral micronized progesterone has been shown to provide adequate endometrial protection in a dose-dependent manner:
- 100 mg daily: Suboptimal endometrial effects 3
- 200 mg daily: Moderate endometrial protection 3
- 300 mg daily: Optimal endometrial protection with responses approaching physiological range 3
Bioavailability studies show that a single 200 mg dose of oral micronized progesterone can achieve peak serum concentrations of 17.0 ± 4.9 ng/ml at approximately 2.8 hours after administration, equivalent to midluteal phase levels in normal cycles 4.
Administration Considerations
- Timing: Bedtime administration is recommended to minimize the impact of side effects such as drowsiness 2
- Duration: For endometrial protection, progesterone must be added for at least 10-14 days per month to prevent hyperplasia and adenocarcinoma 2
- Absorption: Oral progesterone undergoes significant first-pass metabolism (>90%), which limits efficacy of once-daily administration 5
Side Effects and Monitoring
- Common side effects: Mild and transient drowsiness (minimized by bedtime administration) 2
- Monitoring: Clinical review should be performed every 3-6 months initially, then annually 6
- Warning signs: Patients should report any persistent or recurring abnormal vaginal bleeding for appropriate diagnostic evaluation 6
Clinical Pearls
- Micronized progesterone is preferred over synthetic progestins due to fewer metabolic and vascular side effects 2
- The Postmenopausal Estrogens/Progestin Intervention trial recommended oral micronized progesterone as the first choice for opposing estrogen therapy in non-hysterectomized postmenopausal women 2
- Over-the-counter progesterone creams can produce significant drug exposure comparable to FDA-approved oral preparations and should be used with caution 7
Contraindications
- History of hormonally mediated cancers
- Breast cancer
- Undiagnosed vaginal bleeding
- Active thromboembolic disorders
- Current or history of arterial thrombotic disease 6