Hydroxyprogesterone Caproate Injection for Preterm Birth Prevention
Critical Update: Market Withdrawal
Hydroxyprogesterone caproate (17-OHPC) has been removed from the U.S. market, and is no longer available for clinical use. 1
Historical Role and Evidence Base
Primary Indication (No Longer Available)
17-OHPC was previously the preferred progestogen for preventing recurrent preterm birth in women with singleton pregnancies and prior spontaneous preterm birth between 20-36 6/7 weeks gestation. 2
The medication was administered as:
- Dose: 250 mg intramuscularly weekly 2, 3
- Timing: Starting at 16-20 weeks gestation until 36 weeks or delivery 2, 3
Supporting Evidence for Efficacy
The landmark 2003 Meis trial demonstrated substantial benefits in 463 women with prior spontaneous preterm birth: 2, 4
- 34% reduction in recurrent preterm birth at <37 weeks (from 54.9% to 36.3%) 2
- Significant reductions in preterm birth at <32 weeks (11.4% vs 19.6%) and <35 weeks (20.6% vs 30.7%) 2, 4
- Improved neonatal outcomes: reduced intraventricular hemorrhage, necrotizing enterocolitis, and need for supplemental oxygen 2, 4
Why 17-OHPC Was Preferred Over Vaginal Progesterone
The Society for Maternal-Fetal Medicine specifically recommended against substituting vaginal progesterone for 17-OHPC in women with prior spontaneous preterm birth based on: 2
- The 2007 O'Brien trial (659 women) showed no benefit of vaginal progesterone in women with prior preterm birth 2
- The 2011 Hassan trial found no significant difference in women with prior preterm birth (15.8% vs 20.6%; RR 0.77, p=0.60) 2
- The 2016 OPPTIMUM study confirmed lack of benefit in the prior preterm birth subgroup 2
Clinical Pearl: Even when women on 17-OHPC developed cervical shortening, guidelines recommended continuing 17-OHPC rather than switching to vaginal progesterone. 2
Current Clinical Alternatives
For Women with Prior Spontaneous Preterm Birth
With 17-OHPC no longer available, clinicians must now consider alternative strategies, though vaginal progesterone was specifically shown to be ineffective in this population. 2
For Women WITHOUT Prior Preterm Birth but Short Cervix
Vaginal progesterone (90 mg gel or 200 mg suppository) remains effective for singleton pregnancies without prior preterm birth but with cervical length ≤20 mm at 24 weeks. 2, 3
This indication is supported by different evidence showing reduction in preterm birth and perinatal morbidity/mortality in this specific population. 2, 3
Populations Where Progesterone Does NOT Work
Do not use progesterone therapy in: 2, 3
- Multiple gestations (twins, triplets) 2, 3
- Women with preterm labor in current pregnancy 2, 3
- Women with preterm premature rupture of membranes 2, 3
Safety Profile
No long-term adverse effects have been identified in children exposed to progesterone in utero. 3
The medication had a well-established safety profile with no teratogenic effects documented. 5