The effect of the antiprogestin RU 486 on uterine contractility and sensitivity to prostaglandin and oxytocin.
The effect of RU 486, a steroid acting as an antiprogestin at the receptor level, on uterine contractility and sensitivity to the prostaglandin analogue, 16-phenoxy-PGE2 methyl sulfonylamide (16-phenoxy-PGE2) and to oxytocin was studied in 29 women in early pregnancy. Seven untreated women at the same stage of pregnancy served as controls. In the untreated women no spontaneous uterine contractility was recorded and the response to 0.25 mg 16-phenoxy-PGE2 was characterized by an increase in uterine tonus with superimposed irregular contractions of low amplitude. Treatment with 25 mg RU 486 twice daily resulted in the appearance of regular uterine contractions at 24 h in two out of five patients and in all patients at 36, 48 and 72 h after the start of RU 486 treatment. The withdrawal of progesterone influence changed the inactive early pregnant uterus into an active organ. Administration of 16-phenoxy-PGE2 caused an obvious stimulation of both frequency and amplitude of the contractions. In addition, the significantly increased sensitivity to the prostaglandin analogue, but not to oxytocin, was already apparent 24 h after the start of RU 486 treatment. We have previously shown that the addition of one intramuscular injection of 16-phenoxy-PGE2 on the fourth day of treatment with RU 486 (25 mg twice daily) significantly increased the abortifacient effect of the antiprogestin during early pregnancy. The present study suggests that a shorter treatment may be possible.
Swahn
M L
ML
Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden.
Bygdeman
M
M
D000032:Abortion, Therapeutic; D000328:Adult; D015232:Dinoprostone / Q000031:analogs & derivatives*; D004357:Drug Synergism; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015735:Mifepristone; D009215:Myometrium / Q000187:drug effects*; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D011372:Progestins / Q000037:antagonists & inhibitors*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D013997:Time Factors; D014590:Uterine Contraction / Q000187:drug effects*
D004963:Estrenes; D011372:Progestins; D011459:Prostaglandins E, Synthetic; D015735:Mifepristone; D010121:Oxytocin; C016767:sulprostone; D015232:Dinoprostone