Can progesterone be offered as a vaginal cream?

Can Progesterone Be Offered as a Vaginal Cream?

Yes, progesterone can and should be offered vaginally, specifically as either a 90-mg (8%) progesterone gel or 200-mg micronized progesterone capsules/suppositories, particularly for preventing preterm birth in women with a short cervix. 1

Approved Vaginal Formulations

The most extensively studied and recommended vaginal progesterone formulations are:

• 90-mg (8%) progesterone gel administered daily 1
• 200-mg micronized progesterone capsules/suppositories administered daily (typically twice daily as 400 mg total) 1, 2

Both formulations have demonstrated efficacy in high-quality randomized trials and meta-analyses. 1

Primary Clinical Indication: Short Cervix

For singleton pregnancies with cervical length ≤20 mm diagnosed before 24 weeks of gestation, vaginal progesterone is strongly recommended (GRADE 1A) to reduce preterm birth and improve neonatal outcomes. 1

• Vaginal progesterone reduces preterm birth at <33 weeks (RR 0.64,95% CI 0.48-0.86) and significantly decreases composite neonatal morbidity and mortality (RR 0.59,95% CI 0.38-0.91). 1
• For cervical length 21-25 mm, vaginal progesterone should be considered based on shared decision-making (GRADE 1B). 1

Why Vaginal Route Is Preferred

Vaginal administration is the preferred route over oral progesterone for preterm birth prevention because it has stronger evidence for efficacy. 2

• The vaginal route provides a "first-pass effect" that delivers higher local uterine concentrations while minimizing systemic side effects. 3
• Vaginal progesterone avoids the sedative and other systemic side effects commonly seen with oral administration. 3

Important Clinical Caveats

Off-Label Use Requires Counseling

While ACOG recommends vaginal progesterone for short cervix, the FDA has not approved it for this indication, making it off-label use that requires patient counseling. 1

• The FDA declined approval partly because the PREGNANT Trial showed no benefit when analyzing only U.S. patients, and subgroup analyses suggested reduced efficacy in Black patients and those with obesity. 1
• Despite FDA concerns, ACOG and SMFM recommend offering vaginal progesterone given the preponderance of evidence showing benefit and lack of harm. 1

When NOT to Use Vaginal Progesterone

Do not offer vaginal progesterone in:

• Multiple gestations (twins/triplets) - no proven benefit 2
• Active preterm labor - no proven benefit 2
• Preterm premature rupture of membranes - no proven benefit 2
• Women with prior spontaneous preterm birth as primary prevention - use 17-OHPC 250 mg IM weekly instead 1, 2

Dosing Algorithm

For short cervix without prior preterm birth:

• Start vaginal progesterone (90-mg gel daily OR 200-mg capsule twice daily) when short cervix is diagnosed at 18-24 weeks 1
• Continue until 36 weeks of gestation 1

For prior spontaneous preterm birth:

• Use 17-OHPC 250 mg IM weekly starting at 16-20 weeks, NOT vaginal progesterone 1, 2
• If cervical length shortens to ≤25 mm despite 17-OHPC, consider adding cerclage 1

Safety Profile

Vaginal progesterone has an excellent safety profile with no significant adverse effects on maternal or fetal outcomes. 1

• Long-term follow-up studies show no adverse effects on child development or physical examination. 2
• No short-term safety concerns identified in large trials. 2