What are the recommended dosages and uses of progesterone in clinical practice?

Recommended Dosages and Clinical Uses of Progesterone

For prevention of preterm birth and endometrial protection, progesterone should be administered at specific evidence-based dosages tailored to the clinical indication, with 17P 250 mg IM weekly for prior preterm birth and vaginal progesterone 90-200 mg daily for short cervix. 1, 2

Preterm Birth Prevention

Singleton Pregnancies with Prior Spontaneous Preterm Birth (SPTB)

• 17-alpha-hydroxyprogesterone caproate (17P): 250 mg intramuscularly weekly
  • Start: 16-20 weeks gestation
  • Continue until: 36 weeks gestation
  • Evidence shows significant reduction in preterm birth <37 weeks (RR 0.66) and <32 weeks, as well as reduced neonatal morbidity and mortality 1, 2

Singleton Pregnancies with Short Cervical Length (No Prior SPTB)

• Vaginal progesterone: Either 90 mg gel or 200 mg suppository daily
  • Start: At diagnosis of short cervix (≤20 mm on transvaginal ultrasound at ~24 weeks)
  • Continue until: 36 weeks gestation
  • Reduces preterm birth rates by 45% and composite neonatal morbidity/mortality by 43% 1

Management Algorithm for Preterm Birth Prevention

1. For women with prior SPTB: Start 17P at 16-20 weeks
2. For women without prior SPTB but short cervix ≤20 mm: Start vaginal progesterone
3. For women with prior SPTB who develop short cervix <25 mm while on 17P: Continue 17P (insufficient evidence to switch therapies) 1

Populations NOT Benefiting from Progesterone for Preterm Birth Prevention

• Multiple gestations (twins, triplets) without other risk factors
• Preterm labor (for tocolysis)
• Preterm premature rupture of membranes (PPROM)
• Singleton pregnancies without prior SPTB or short cervix 1, 2

Hormone Replacement Therapy

Prevention of Endometrial Hyperplasia

• Oral micronized progesterone: 200 mg daily
  • Administration: At bedtime for 12 continuous days per 28-day cycle
  • Used in postmenopausal women with intact uterus who are receiving estrogen therapy
  • Reduces risk of endometrial hyperplasia from 64% (estrogen alone) to 6% (with progesterone) 3

Secondary Amenorrhea

• Oral micronized progesterone: 400 mg daily
  • Administration: At bedtime for 10 days
  • Results in withdrawal bleeding in approximately 80% of women within 7 days of the last dose 3
  • Alternative dosing: 300-400 mg daily for 10 days during two 28-day treatment cycles 3

Premature Ovarian Insufficiency (POI)

• Begin cyclic progestogens after at least 2 years of estrogen therapy or when breakthrough bleeding occurs 1
• For adolescents with POI (e.g., Turner Syndrome):
  • Start progestogen after 2 years of estrogen or when breakthrough bleeding occurs
  • Oral micronized progesterone: 100-200 mg/day or dydrogesterone 5-10 mg/day during 12-14 days of the month 1

Administration Considerations

• Oral progesterone: Take at bedtime with a glass of water while standing to minimize difficulty swallowing and reduce drowsiness side effects 3
• Vaginal progesterone: Available as gel or suppository formulations, allowing for self-administration with fewer systemic side effects 2
• 17P: Requires weekly office visits for intramuscular injection, may cause local injection site pain 2

Common Side Effects and Precautions

• Oral progesterone: Drowsiness, dizziness, headaches, breast pain, irregular vaginal bleeding, abdominal cramps, nausea 3
• Contraindications: Unusual vaginal bleeding, certain cancers, history of stroke/heart attack, blood clots, liver problems, peanut allergy (oral formulation contains peanut oil) 3

Clinical Pearls

1. When using progesterone for endometrial protection, the minimum effective dose should be prescribed to reduce side effects 4
2. For postmenopausal women, continuous daily progestin maintains the endometrium in an inactive phase in 100% of women, while cyclic progestin achieves this in only 25% 5
3. Vaginal progesterone achieves higher uterine concentrations despite lower systemic levels due to direct vagina-to-uterus transport 6
4. For prevention of miscarriage, progesterone may benefit women with previous miscarriages and current pregnancy bleeding, but is not recommended for the general population 2
5. Take oral progesterone at bedtime to minimize drowsiness side effects 7

By following these evidence-based recommendations for progesterone dosing and administration, clinicians can optimize outcomes while minimizing side effects across various clinical indications.