What is the recommended dosage and administration of progesterone (P4) for supporting early pregnancy or managing menopausal symptoms?

Recommended Dosage and Administration of Progesterone for Early Pregnancy Support and Menopausal Symptoms

For prevention of preterm birth in singleton pregnancies with prior spontaneous preterm birth, 17-alpha-hydroxyprogesterone caproate (17P) 250 mg IM weekly starting at 16-20 weeks until 36 weeks is recommended; for menopausal symptoms, oral micronized progesterone 200 mg daily for 12 days per 28-day cycle is the preferred regimen when combined with estrogen therapy. 1, 2

Progesterone for Prevention of Preterm Birth

Singleton Pregnancies with Prior Spontaneous Preterm Birth (SPTB)

• First-line therapy: 17P 250 mg IM weekly 1
  • Start: 16-20 weeks gestation
  • Continue until: 36 weeks gestation
  • Evidence shows significant reduction in recurrent preterm birth rates

Singleton Pregnancies with Short Cervical Length (CL) but No Prior SPTB

• Recommended regimen: Vaginal progesterone for women with CL ≤20 mm at 24 weeks 1
  • Option 1: 90 mg vaginal gel daily until 36 weeks
  • Option 2: 200 mg vaginal suppository daily until 36 weeks
  • Both formulations show reduction in preterm birth and perinatal morbidity/mortality

Important Clinical Considerations

• If a woman with prior SPTB develops short cervix (≤25 mm) at 24 weeks while on 17P, cervical cerclage may be offered 1
• For women with PPROM who were already receiving 17P for prior SPTB, it's reasonable to continue 17P after membrane rupture 1
• Progesterone is NOT recommended for:
  • Multiple gestations (twins, triplets)
  • Preterm labor
  • Women without risk factors
  • Primary tocolysis

Progesterone for Menopausal Symptoms

Hormone Replacement Therapy

• Standard regimen: Progesterone capsules 200 mg daily for 12 days per 28-day cycle in combination with conjugated estrogens 2
  • This regimen significantly reduces the risk of endometrial hyperplasia compared to estrogen-only therapy (6% vs 64%)
  • Must be combined with estrogen for symptom relief

Secondary Amenorrhea Management

• Recommended regimen: 300-400 mg oral progesterone daily for 10 days 2
  • 300 mg daily induces withdrawal bleeding in 73.8% of women
  • 400 mg daily induces withdrawal bleeding in 76.8% of women

Route of Administration Considerations

Vaginal Progesterone

• Preferred for preterm birth prevention with short cervix
• Better local effect on cervix
• Fewer systemic side effects
• Options: gel (90 mg) or suppository (200 mg)

Intramuscular 17P

• Preferred for history of prior preterm birth
• Weekly administration improves compliance
• More consistent blood levels

Oral Micronized Progesterone

• Preferred for menopausal symptoms
• Better bioavailability than older oral formulations
• Take at bedtime to minimize drowsiness side effect 3
• More favorable metabolic and vascular profile than synthetic progestins 3

Safety Considerations and Contraindications

• Progesterone therapy should be avoided in women with:

  • Current or past ER+ breast cancer
  • High risk for developing breast cancer (BRCA1/2 mutations)
  • History of thromboembolic disorders 4

• Side effects of oral micronized progesterone are generally mild:

  • Transient drowsiness (minimized by bedtime administration)
  • Less metabolic and vascular side effects compared to synthetic progestins 3

Monitoring

• For preterm birth prevention: Regular cervical length monitoring, especially in high-risk women
• For menopausal symptoms: Monitor for breakthrough bleeding and endometrial changes
• Discontinue if adverse effects occur or if contraindications develop

The evidence strongly supports these specific dosing regimens for the prevention of preterm birth and management of menopausal symptoms, with the choice of formulation and route dependent on the specific indication.