What is the recommended dosage and administration of progesterone (a steroid hormone) for therapeutic use?

Recommended Dosage and Administration of Progesterone for Therapeutic Use

For therapeutic use, progesterone should be administered according to specific indications, with oral progesterone given as 200 mg daily at bedtime for 12 days per 28-day cycle for prevention of endometrial hyperplasia, and 400 mg daily at bedtime for 10 days for treatment of secondary amenorrhea. 1

Oral Progesterone Administration

Prevention of Endometrial Hyperplasia

• 200 mg oral progesterone capsules once daily at bedtime
• Given for 12 days sequentially per 28-day cycle
• Indicated for postmenopausal women with a uterus who are receiving daily conjugated estrogen therapy 1
• Should be taken with a glass of water while standing if swallowing difficulties occur 1

Treatment of Secondary Amenorrhea

• 400 mg oral progesterone capsules once daily at bedtime
• Given for 10 days
• Approximately 80% of women experience withdrawal bleeding within 7 days of completing treatment 2

Vaginal Progesterone Administration

For Prevention of Preterm Birth

• For women with singleton pregnancy and prior spontaneous preterm birth:

  • 17-alpha hydroxyprogesterone caproate (17P) 250 mg IM weekly from 16-20 weeks until 36 weeks 3

• For women with singleton pregnancy without prior preterm birth but with short cervical length:

  • Cervical length ≤20 mm: Vaginal progesterone 90 mg gel or 200 mg suppository daily from diagnosis until 36 weeks 3
  • Cervical length 21-25 mm: Consider vaginal progesterone based on shared decision-making 3

For Threatened Miscarriage

• For women with previous miscarriage and threatened miscarriage in early pregnancy:
  • Vaginal micronized progesterone twice daily until 12 weeks of pregnancy 4
  • Note: While some guidelines recommend continuing until 16 weeks, evidence suggests benefits are complete by 12 weeks 4

Administration Considerations

Oral Progesterone

• Should be taken at bedtime due to potential drowsiness and dizziness 2, 5
• May cause blurred vision or difficulty speaking/walking in some women 2
• Has >90% first-pass metabolism, limiting efficacy of once-daily administration 5
• Taking with water while standing may help with swallowing difficulties 1

Vaginal Progesterone

• Provides better bioavailability than oral administration 5
• Allows for secretory transformation of the endometrium despite lower systemic progesterone concentrations 5
• Formulations include gel and suppositories, with bioadhesive characteristics providing controlled release 5
• In pregnancy, vaginal progesterone produces only minimal increases in systemic levels (median 24% increase over baseline) 6

Contraindications and Precautions

• Progesterone therapy is contraindicated in:
  • Known or suspected pregnancy (except for specific indications)
  • Undiagnosed vaginal bleeding
  • Active thromboembolic disorders
  • History of arterial thrombotic disease
  • Current or history of hormone-dependent cancers
  • Liver problems
  • Peanut allergy (for formulations containing peanut oil) 2

Monitoring Recommendations

• Initial evaluation at 3-6 months after starting therapy
• Subsequent annual clinical reviews
• Monitor for persistent or recurrent abnormal vaginal bleeding
• Assess symptom control and compliance 2

Clinical Pearls

• Natural (micronized) progesterone has a better safety profile than synthetic progestins, with lower risk of breast cancer and no negative impact on lipid profiles 2
• Progesterone is ineffective for multiple gestations, preterm labor, or preterm premature rupture of membranes 3, 2
• For women with prior preterm birth receiving 17P who experience preterm premature rupture of membranes, it is reasonable to continue 17P 3
• Vaginal administration provides preferential uterine uptake of progesterone through direct vagina-to-uterus transport 5

By following these specific dosing recommendations based on indication, healthcare providers can optimize progesterone therapy while minimizing potential side effects.