Analysis of a study of menses induction using a vaginal suppository containing 3.0 mg 15(S)-15-methyl-PGF2α methyl ester

Abstract

Peripheral blood levels of 15-methyl-PGF2α, human chorionic gonadotropin (hCG) and progesterone were determined in patients treated for the induction of menses with a single vaginal suppository containing 3.0 mg 15(S)-15-methyl-PGF2α methyl ester. The mean blood levels of 15-methyl-PGF2α were higher in the successful cases than in the failures or in cases that were defined as partial successes. The plasma level of 15-methyl-PGF2α increased faster in the successful cases than in the failure cases, and was maintained at elevated levels longer in the successful cases than in the partially successful cases. Serum concentrations of hCG declined following treatment in both the successful and unsuccessful cases. At the follow-up visit (approximately 2 weeks after treatment), the level of hCG was significantly lower in the successful cases than in the unsuccessful cases. Serum concentrations of progesterone did not change significantly in any of the groups during the first 10 hr after treatment. However, at the follow-up visit the concentration of progesterone in the successful cases was significantly lower than in the failure cases. A larger percentage of the patients in whom menses was successfully induced had gastrointestinal side effects than patients who were considered treatment failures. This analysis has demonstrated a distinct relationship between blood levels of 15-methyl-PGF2α and the efficacy of these vaginal suppositories for menses induction. The successful induction of menses was associated with a more rapid increase in the plasma concentration of 15-methyl-PGF2α and with mean concentrations of drug that were significantly higher than in the cases that were considered failures. The higher blood levels of drug were also associated with a higher incidence of gastrointestinal side effects. The experience accumulated to date indicates that a vaginal delivery system for 15(S)-15-methyl-PGF2α methyl ester that releases the drug faster and in a more predictable fashion than the vaginal suppository is required for the successful induction of menses.