Numerous studies have shown that PGE2, PGF2α, and their analogs effectively initiate and stimulate labor, but PGF2α is one tenth as potent as PGE2. There appears to be no difference in the efficacy of PGE2 and PGF2α when they are administered intravenously; however, the most common usage is local application of PGE2 analogs (dinoprostone) to promote labor through ripening of the cervix. These agents and oxytocin have similar success rates and comparable induction-to-delivery intervals. The adverse effects of the prostaglandins are moderate, with a slightly higher incidence of nausea, vomiting, and diarrhea than that produced by oxytocin. PGF2α has more gastrointestinal toxicity than PGE2. Neither drug has significant maternal cardiovascular toxicity in the recommended doses. In fact, PGE2 must be infused at a rate about 20 times faster than that used for induction of labor to decrease blood pressure and increase heart rate. PGF2α is a bronchoconstrictor and should be used with caution in women with asthma; however, neither asthma attacks nor bronchoconstriction have been observed during the induction of labor. Although both PGE2 and PGF2α pass the fetoplacental barrier, fetal toxicity is uncommon.
For the induction of labor or softening of the cervix, dinoprostone is used either as a gel (0.5 mg PGE2 every 6 hours; maximum 24-hour cumulative dose of 1.5 mg) or as a controlled-release vaginal insert (10 mg PGE2) that releases PGE2 over 12 hours. The softening of the cervix for induction of labor substantially shortens the time to onset of labor and the delivery time. An advantage of the controlled-release formulation is a lower incidence of gastrointestinal effects (<1% versus 5.7%).
The effects of oral PGE2 administration (0.5–1.5 mg/h) have been compared with those of intravenous oxytocin and oral demoxytocin, an oxytocin derivative, in the induction of labor. Oral PGE2 is superior to the oral oxytocin derivative and in most studies is as efficient as intravenous oxytocin. Oral PGF2α causes too much gastrointestinal toxicity to be useful by this route.
Theoretically, PGE2 and PGF2α should be superior to oxytocin for inducing labor in women with preeclampsia-eclampsia or cardiac and renal diseases because, unlike oxytocin, they have no antidiuretic effect. In addition, PGE2 has natriuretic effects. However, the clinical benefits of these effects have not been documented. In cases of intrauterine fetal death, the prostaglandins alone or with oxytocin seem to cause delivery effectively.
C. Dysmenorrhea
Primary dysmenorrhea is attributable to increased endometrial synthesis of PGE2 and PGF2α during menstruation, with contractions of the uterus that lead to ischemic pain. NSAIDs successfully inhibit the formation of these prostaglandins (see Chapter 36) and so relieve dysmenorrhea in 75–85% of cases. Some of these drugs are available over the counter. Aspirin is also effective in dysmenorrhea, but because it has low potency and is quickly hydrolyzed, large doses and frequent administration are necessary. In addition, the acetylation of platelet COX, causing irreversible inhibition of platelet TXA2 synthesis, may increase the amount of menstrual bleeding.