Progesterone Therapy: Indications and Dosing Regimens
Progesterone therapy is indicated primarily for prevention of preterm birth in specific high-risk populations, with 17-alpha-hydroxyprogesterone caproate (17P) recommended for women with prior spontaneous preterm birth and vaginal progesterone for women with short cervical length. 1, 2
Primary Indications for Preterm Birth Prevention
Singleton Pregnancies with Prior Spontaneous Preterm Birth
- Recommended regimen: 17P 250 mg intramuscularly weekly
- Timing: Start at 16-20 weeks gestation until 36 weeks gestation or delivery
- Evidence: Significantly reduces rates of preterm birth <37 weeks and <32 weeks, as well as neonatal morbidity and mortality 1, 2
Singleton Pregnancies with Short Cervical Length
- Recommended regimen: Vaginal progesterone 90 mg gel or 200 mg suppository daily
- Timing: From diagnosis of short cervical length (≤20 mm at ≤24 weeks) until 36 weeks gestation
- Evidence: Significantly reduces preterm birth rates and perinatal morbidity/mortality 1, 2
Populations Where Progesterone Is NOT Effective
Progesterone therapy has shown no benefit in the following scenarios:
- Multiple gestations (twins, triplets) without other risk factors
- Preterm labor (for tocolysis)
- Preterm premature rupture of membranes (PPROM)
- Singleton pregnancies without prior spontaneous preterm birth or short cervix 1, 2
Route-Specific Considerations
Intramuscular 17P (250 mg weekly)
- Preferred for: Women with history of spontaneous preterm birth
- Advantages: Well-studied in large trials
- Disadvantages: Local injection site pain, requires weekly office visits 1
Vaginal Progesterone
- Preferred for: Women with short cervical length
- Formulations:
- 90 mg gel daily
- 200 mg suppository daily
- Advantages: Fewer systemic side effects, self-administration 1, 2
Special Situations
Women with Both Prior Preterm Birth and Short Cervix
- Continue 17P if already initiated
- If cervix shortens to ≤25 mm while on 17P, reasonable to continue 17P rather than switching to vaginal progesterone 1
- Consider cervical cerclage in women with cervical length ≤15 mm 1
PPROM in Women Already on Progesterone
- Reasonable to continue 17P if already being used for prior spontaneous preterm birth 1
Monitoring and Follow-up
- For women with prior preterm birth: Start 17P at 16-20 weeks
- For women at risk of short cervix: Consider transvaginal ultrasound cervical length screening at 18-24 weeks
- If short cervix is identified, begin vaginal progesterone immediately
Comparative Efficacy
While some small studies suggest similar efficacy between vaginal progesterone and 17P for prevention of recurrent preterm birth 3, the Society for Maternal-Fetal Medicine recommends 17P specifically for women with prior spontaneous preterm birth, stating that "vaginal progesterone should not be considered a substitute for 17OHP-C in these patients" 1.
Pitfalls and Caveats
- Do not use progesterone for tocolysis in active preterm labor
- Do not use in multiple gestations without other risk factors
- Ensure proper timing of initiation (16-20 weeks for 17P)
- Recognize that progesterone therapy will reduce preterm birth rates by less than 0.5% in general population screening programs 4
- For women with prior preterm birth who develop cervical shortening while on 17P, continuing 17P rather than switching to vaginal progesterone is recommended 1