What are the progesterone options and formulations for treating threatened abortion?

Progesterone Options and Formulations for Threatened Abortion

For threatened abortion, oral micronized progesterone at 400 mg daily (200 mg twice daily) is the most evidence-supported option, with the addition of intramuscular progesterone 500 mg/day showing superior anti-inflammatory effects in severe cases. 1

Progesterone Formulations Available

Oral Progesterone

• Micronized progesterone capsules:
  • Available in 100 mg and 200 mg strengths 2
  • Contains peanut oil (important contraindication in patients with peanut allergy) 2
  • Typical dosing: 200 mg twice daily (400 mg/day) 1
  • Advantages: Non-invasive, convenient administration

Vaginal Progesterone

• Vaginal suppositories/gel:
  • Dosing options:
    • 400 mg daily 3, 4
    • 90 mg gel or 200 mg suppository 3
  • Advantages: Higher bioavailability, direct delivery to target tissue
  • Particularly effective in cases with short cervical length ≤20 mm 3

Injectable Progesterone

• Intramuscular (IM) progesterone:
  • Options include:
    • 17P (17-alpha-hydroxyprogesterone caproate): 250-500 mg weekly or 341 mg twice weekly 3
    • Depot progesterone: 500 mg/day 1
  • Used as adjunctive therapy in severe cases or when oral/vaginal routes are insufficient 1

Evidence-Based Treatment Protocols

First-Line Therapy

• Oral micronized progesterone: 200 mg twice daily (400 mg/day) for threatened abortion 1
  • Studies show this dose reduces proinflammatory cytokines (IL-6, TNF-α) and increases anti-inflammatory cytokines (IL-10) 1
  • Demonstrated increased placental volume compared to control groups (336% vs 141%, p=0.007) 5

For More Severe Cases

• Combined therapy: Oral micronized progesterone 200 mg twice daily PLUS intramuscular depot progesterone 500 mg/day 1
  • Shows superior anti-inflammatory effects compared to oral therapy alone 1
  • Greatest reduction in TNF-α and IL-6 levels, with highest increase in IL-10 1

For Maintenance After Threatened Abortion

• Continue progesterone until bleeding stops (typically within one week) 4
• For patients with history of recurrent abortion, consider continuing through first trimester 6

Monitoring and Efficacy Assessment

• Serum progesterone levels can guide therapy:
  • Levels below 15 ng/ml in first 10 weeks of gestation suggest corpus luteum dysfunction 6
  • Target progesterone levels should be normalized to reduce abortion risk 6
• Elevated IL-6 (>12.01) and TNF-α (>11.04) levels increase abortion risk and may indicate need for more aggressive therapy 1

Important Considerations

• Progesterone treatment for threatened abortion has not been associated with increased risk of pregnancy complications, preterm birth, or low birth weight 7
• Treatment success is measured by pregnancy continuation beyond 20 weeks gestation 4
• Peanut oil in oral formulations is a contraindication for patients with peanut allergies 2
• While vaginal progesterone shows good efficacy, oral administration with appropriate dosing may be more acceptable to some patients

Clinical Pitfalls to Avoid

• Underdosing progesterone (doses below 400 mg/day show less efficacy) 1
• Discontinuing therapy too early (continue until bleeding resolves completely)
• Failing to consider combined therapy (oral + IM) in severe cases with high inflammatory markers 1
• Not monitoring serum progesterone levels in patients with recurrent abortion history 6

By following these evidence-based recommendations, the likelihood of successful pregnancy continuation beyond 20 weeks can be significantly improved in women experiencing threatened abortion.