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The finding that exogenous prostaglandins have a potent and specific stimulatory action on uterine contractility in the human female as well as data suggesting increased concentrations of endogenous prostaglandins in amniotic fluid and blood serum during labor indicate that these compounds may play a role in human parturition. However, earlier results on blood levels of prostaglandin F2α(PGF2α) remain controversial because of the possible formation of PGF2αby platelets and blood cells during isolation of the plasma or serum. It seems that measurement of the PGF2αmetabolite 15-keto-13, 14-dihydro-PGF2αby a gas chromatographic-mass spectrometric technique offers a more reliable method for monitoring PGF2αbiosynthesis. During the last month preceding labor, the concentration of 15-keto-13, 14-dihydro-PGF2αincreased slightly. During active labor the plasma level of the metabolite increased ten- to thirtyfold. One hour after delivery the concentration had decreased by 20 to 75 per cent. The presented data support the view that endogenously produced PGF2αresults in increased uterine activity during the last month of pregnancy and during labor.

15(S)15-methyl-PGF2α-methyl ester was administered as vaginal suppositories to terminate very early gestation in 16 outpatients who were thought to be pregnant. All patients received between 2.5 and 5.0 mg. of the prostaglandin compound. Pregnancy was confirmed later in 10 of the women. In these patients vaginal bleeding started 3 to 6 hours after the start of therapy and continued for an average of 8 days. By subjective assessment, the amount of bleeding during this time was equal to or slightly heavier than that of a normal menstruation for each woman. Patients were followed for 2 to 4 weeks with serial measurements of serum progesterone and HCG. There were no failures at early pregnancy interruption. Gastrointestinal side effects rarely were encountered; no serious complications occurred and no curettage had to be performed because of heavy bleeding. The vaginal use of the methyl ester of 15(S)15-methyl-PGF2αfor the termination of early pregnancy seems promising as a reliable and practical outpatient procedure.

The effect of single intravenous and intramuscular injections as well as intra-amniotic and vaginal administration of PGE1on the motility of the midpregnant human uterus was studied. Recording of uterine motility was made by measuring the amniotic pressure. Intravenous and intramuscular PGE1stimulated the uterus predominantly by elevation of tone. The threshold dose of intravenous injection was found to be around 20 μg. One hundred micrograms caused a long-lasting sustained contracture. The influence of intravenous injection of PGE2was compared with that of PGE1and found to be approximately the same both qualitatively and quantitatively. Intra-amniotic or vaginal administration of PGE1in high doses had no effect whatsoever on the pregnant uterus.

The effect of intravenous infusion of the pure prostaglandin compounds PGE1and PGE2on the motility of the pregnant human uterus was studied. Recording of uterine motility was made by measuring the amniotic pressure. Nine midpregnant and 8 term pregnant patients were studied. Both PGE1and PGE2stimulated uterine motility in all experiments. The potency of PGE1was approximately the same as that of PGE2. The midpregnant uterus was somewhat more sensitive to both compounds than the uterus at term. Threshold dose at midpregnancy was 2 to 4 μg per minute and at term 4 to 8 μg per minute. At midpregnancy the PGE compounds preferably induced an increment of tone but to some extent also an irregular uterine activity. At term the effect on amplitude and frequency of contractions was more dominant but unphysiologic elevation of tone frequently occurred. The latter reaction renders the PGE substances less suitable for induction of labor, whereas their tendency to cause longlasting uterine contracture might offer a group of new pharmacologic agents for the treatment of uterine atonicity after delivery.

The influence of single intravenous injections of two prostaglandin F compounds (PGF1αand PGF2α) on the motility of the pregnant human uterus in situ was studied. It was found that PGF2αand to some minor extent PGF1αhad a stimulatory effect, predominantly in terms of elevation of tone. The threshold dose of PGF2αwas approximately 8 times higher than that of PGE1.