What are the gynecological indications for progesterone therapy?

Gynecological Indications for Progesterone Therapy

Progesterone therapy is primarily indicated for prevention of preterm birth in women with singleton pregnancies who have a history of spontaneous preterm birth, with 17-alpha hydroxyprogesterone caproate (17OHP-C) being the recommended first-line agent for this indication. 1

Prevention of Preterm Birth

Women with Prior Spontaneous Preterm Birth

• 17OHP-C 250 mg intramuscularly weekly from 16-20 weeks until 36 weeks gestation is the recommended treatment for women with singleton pregnancies and history of spontaneous preterm birth between 20-36 6/7 weeks 1, 2
• This recommendation is based on strong evidence showing:
  • 34% reduction in recurrent preterm birth at <37 weeks
  • Significant reductions in preterm birth at <32 and <35 weeks
  • Significant reductions in infant complications including intraventricular hemorrhage, necrotizing enterocolitis, and need for supplemental oxygen 1

Women with Short Cervical Length

• For women with singleton pregnancies and short cervical length ≤20 mm at 24 weeks (without prior preterm birth):
  • Vaginal progesterone (90 mg gel or 200 mg suppository daily) until 36 weeks is recommended 1, 2, 3
  • This significantly reduces preterm birth rates and perinatal morbidity/mortality 1, 3

Management of Cervical Shortening During Treatment

• If cervix shortens to ≤25 mm while on 17OHP-C, cervical cerclage may be offered 1, 2
• The Society for Maternal-Fetal Medicine emphasizes that vaginal progesterone should not be considered a substitute for 17OHP-C in women with prior spontaneous preterm birth 2

Other Gynecological Indications

Secondary Amenorrhea

• Oral micronized progesterone is FDA-approved for treatment of secondary amenorrhea 4
• This helps restore normal menstrual cycles in women with absent periods not due to pregnancy or menopause

Prevention of Endometrial Hyperplasia

• Progesterone capsules are indicated for prevention of endometrial hyperplasia in non-hysterectomized postmenopausal women receiving conjugated estrogens 4, 5
• Oral micronized progesterone (typically 200 mg for 14 days a month or 100 mg for 25 days a month) is recommended as first-line therapy for opposing estrogen effects on the endometrium 5

Prevention of Miscarriage in Select Populations

• For women with three or more previous miscarriages and current pregnancy bleeding, vaginal micronized progesterone may increase live birth rates (72% vs 57%) 2
• However, progesterone is not recommended for miscarriage prevention in the general population or in women with threatened miscarriage without other risk factors 2

Populations Not Benefiting from Progesterone Therapy

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

Administration Routes and Considerations

• 17OHP-C (intramuscular): Well-studied in large trials but requires weekly office visits and may cause injection site pain 2
• Vaginal progesterone: Fewer systemic side effects, self-administered, but less extensively studied for some indications 2, 6
• Oral micronized progesterone: Useful for endometrial protection and amenorrhea; may cause mild drowsiness (recommended administration at bedtime) 5
• Transdermal progesterone: Insufficient evidence to support use, particularly for endometrial protection 6

Clinical Pitfalls to Avoid

• Do not substitute vaginal progesterone for 17OHP-C in women with prior spontaneous preterm birth, as studies show superior outcomes with 17OHP-C in this specific population 1, 2
• Do not delay initiation of progesterone therapy beyond 20 weeks in high-risk women, as efficacy decreases with later initiation 1
• Avoid using progesterone in populations where it has not shown benefit (multiple gestations, active preterm labor, PPROM) 1, 2
• Do not rely on transdermal progesterone preparations for endometrial protection during estrogen therapy 6