Timing of Progesterone Administration for Hormone Replacement Therapy
Take progesterone at bedtime as a single daily dose to minimize side effects, particularly dizziness and drowsiness that can impair your ability to drive or operate machinery. 1
Bedtime Dosing: The Standard Recommendation
The FDA-approved labeling for oral progesterone explicitly states that progesterone capsules should be taken at bedtime because some women experience significant drowsiness, dizziness, blurred vision, difficulty speaking, difficulty walking, and feeling abnormal after taking the medication 1. This timing strategy serves two critical purposes:
- Safety consideration: Taking progesterone while standing with a glass of water at bedtime reduces the risk of experiencing these neurological side effects during waking hours when you need to function normally 1
- Metabolic rationale: Oral progesterone undergoes extensive first-pass hepatic metabolism (>90%), producing high levels of 5-alpha reduced metabolites that cause sedation 2. By timing administration at bedtime, these sedative effects align with your natural sleep cycle
Dosing Regimens Based on Clinical Indication
For Prevention of Endometrial Hyperplasia (Standard HRT)
Sequential regimen: Take 200 mg oral micronized progesterone at bedtime for 12 consecutive days per 28-day cycle 1, 3. This is the FDA-approved dosing for postmenopausal women with a uterus taking estrogen therapy.
Alternative sequential options if micronized progesterone is unavailable:
- Medroxyprogesterone acetate 10 mg daily at bedtime for 12-14 days per month 3
- Dydrogesterone 10 mg daily at bedtime for 12-14 days per month 3
Continuous regimen: If you prefer to avoid monthly bleeding, lower daily doses can be used:
For Secondary Amenorrhea
Take 400 mg oral progesterone as a single daily dose at bedtime for 10 days 1. This higher dose is necessary to induce withdrawal bleeding in women with absent menstrual periods.
Pharmacokinetic Support for Bedtime Dosing
Research demonstrates that when progesterone is administered twice daily (100 mg morning, 200 mg evening), peak plasma concentrations occur 2 hours after ingestion 4. The evening dose produces sustained elevations in biologically active metabolites for at least 12 hours 4. However, the standard clinical practice remains once-daily bedtime dosing rather than split dosing, as this provides adequate endometrial protection while minimizing daytime side effects 1, 5.
Critical Safety Warnings
- Do not drive or operate machinery if you experience dizziness, drowsiness, blurred vision, or difficulty walking after taking progesterone 1
- If you have difficulty swallowing the capsules, take them at bedtime while standing with a full glass of water 1
- The sedative effects are most pronounced during initial therapy and may improve with continued use 2
Why Micronized Progesterone is Preferred
Micronized progesterone is recommended over synthetic progestins because it has a superior safety profile with lower cardiovascular and thrombotic risks 3. When taken at bedtime, the main side effect—transient drowsiness—becomes therapeutic rather than problematic 5. Studies show that 300 mg micronized progesterone taken at bedtime for 10 days per month provides excellent endometrial protection with minimal side effects 5.
Common Pitfall to Avoid
Never take progesterone in the morning unless specifically instructed by your healthcare provider for a particular clinical indication. The sedative metabolites produced by oral progesterone can significantly impair your cognitive and motor function during daytime hours 1, 2. The bedtime dosing strategy is not merely a suggestion—it is a safety measure built into the FDA-approved prescribing information 1.