EFFECT OF LOW DAILY DOSES OF MIFEPRISTONE ON OVARIAN-FUNCTION AND ENDOMETRIAL DEVELOPMENT

The effects of low daily doses of the antiprogestin mifepristone (RU 4 86) on ovarian and endometrial function were studied. The study includ ed one control cycle, three treatment cycles and one follow-up cycle. During the treatment cycles, either 0.1 (n = 5) or 0.5 (n = 5) mg of m ifepristone was administered once daily. Urine samples were collected three times weekly during the control and treatment cycles and pregnan ediol glucuronide and oestrone glucuronide and luteinizing hormone (LI ) were quantified by radioimmunoassay. Blood samples for cortisol meas urement were collected once weekly and for serum glycodelin at the ons et of menstruation. An endometrial biopsy was obtained in the mid-lute al phase in the control cycle and in the first and third treatment cyc les and analysed by morphometric and histochemical methods. Binding of Dolichus biflorus agglutinin (DBA) lectin was measured and expression of progesterone and oestrogen receptors and glycodelin were analysed immunohistochemically. All cycles studied were ovulatory with an LH pe ak and elevated pregnanediol glucuronide concentrations. Follicular de velopment seemed normal as judged by ultrasound examination. The lengt h of the menstrual cycle and the menstrual bleeding were not significa ntly altered. Following administration of 0.5 mg mifepristone/day, end ometrial development appeared to be slightly retarded and glandular di ameter was significantly reduced. Furthermore, significant decreases i n DBA lectin binding and endometrial expression of glycodelin were obs erved. Daily doses of 0.1 mg did not have any significant effect on th e endometrium. No differences in oestrogen or progesterone receptor im munoactivity between control and treatment cycles mere seen. This stud y provides further evidence that endometrial function is sensitive eve n to doses of antiprogestin that are low enough not to disturb ovulati on. It remains to be established whether these effects are sufficient to prevent implantation.