EFFECT OF MIFEPRISTONE (RU486) ON THE PITUITARY-RESPONSE TO GONADOTROPIN-RELEASING-HORMONE IN WOMEN

Mifepristone interrupts folliculogenesis in women but the mechanism is not clear, Previous studies have investigated the effect of this comp ound on gonadotrophin secretion and have provided conflicting results. To study further the effect of mifepristone on basal and gonadotrophi n-releasing hormone (GnRH)-induced gonadotrophin secretion, 12 normall y ovulating women were investigated during two consecutive menstrual c ycles, comprising an untreated cycle (control) and a cycle treated wit h mifepristone. All women were treated with mifepristone on days 2-8 a t the dose of 100 mg (group 1, eight women) or 10 mg per day (group 2, six women). Two women were treated with both regimens in two differen t cycles. On day 8 of both cycles, the women received two GnRH pulses of 10 mu g each 2 h apart. Blood samples in relation to the first GnRH pulse were taken at -15, 0, 30, 60, 120, 150, 180 and 240 min. In gro up I, the increase in luteinizing hormone (Delta LH) in response to Gn RH was significantly attenuated from 30 to 180 min, while the increase in follicle stimulating hormone (Delta FSH) was attenuated only in re sponse to the second GnRH pulse. No significant decrease in Delta LH a nd Delta FSH response to Gn:RH was seen during treatment with the 10 m g dose (group 2). In group 1, serum oestradiol and inhibin-A concentra tions after day 8 were lower than in the control cycles and the LH pea k was postponed by 7 days on average. Basal LH values increased signif icantly on day 8 in both groups, while FSH values did not change signi ficantly compared with the control cycles. A significant increase in s erum progesterone and cortisol values occurred during the treatment on ly in group 1. Mid-luteal values of inhibin-A were significantly lower in cycles treated with 100 mg mifepristone than in the control cycles . We conclude that the disruption of folliculogenesis by mifepristone cannot be explained by a decrease in basal FSH concentrations during t he critical period of follicle recruitment and selection. It is possib le that mifepristone exerts its effect at the level of the ovary. It i s also suggested that progesterone during the follicular phase of the cycle may participate in the control of the self-priming action of GnR H on the pituitary.