Actions of progestins for the inhibition of cervical ripening and uterine contractions to prevent preterm birth

The importance of progesterone (P4) for maintenance of pregnancy, its role in cervical ripening and uterine contractions is at least partly established and therefore, not surprisingly, the basis for the concept to use P4 as a treatment for preterm birth. Due to the complexity of the condition of preterm birth there are still questions concerning the optimal population that might benefit, timing of treatment, dosage, vehicle and route of administration. Recently vaginal P4 and intramuscular 17-alpha-hydroxyprogesterone caproate (17P) have been used to prevent preterm birth in patients with a high risk for early delivery. The aim of this study was to assess cervical changes throughout pregnancy in rats and the timing of term and preterm delivery after various progestin treatments given by different routes and vehicles in hope of identifying better treatment regimens. This paper presents results that suggest that there are better routes of treatment than the vaginal route (e.g. topical), that the vehicle used in many of the clinical studies (Replens®) is not appropriate due to a low release of the steroid and consequently low uptake of P4, and that inhibition of birth is primarily due to inhibition of uterine contractility that can be achieved by supplementation of P4 but not with 17P.