Endocrinology: Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women

Mifepristone interrupts folliculogenesis in women but the mechanismis not clear. Previous studies have investigated the effectof this compound on gonadotrophin secretion and have providedconflicting results. To study further the effect of mifepristoneon basal and gonadotrophin-releasing hormone (GnRH)-inducedgonadotrophin secretion, 12 normally ovulating women were investigatedduring two consecutive menstrual cycles, comprising an untreatedcycle (control) and a cycle treated with mifepristone. All womenwere treated with mifepristone on days 2–8 at the doseof 100 mg (group 1, eight women) or 10 mg per day (group 2,six women). Two women were treated with both regimens in twodifferent cycles. On day 8 of both cycles, the women receivedtwo GnRH pulses of 10 µg each 2 h apart. Blood samplesin relation to the first GnRH pulse were taken at –15,0, 30, 60, 120, 150, 180 and 240 min. In group 1, the increasein luteinizing hormone (LH) in response to GnRH was significantlyattenuated from 30 to 180 min, while the increase in folliclestimulating hormone (FSH) was attenuated only in response tothe second GnRH pulse. No significant decrease in LH and FSHresponse to GnRH was seen during treatment with the 10 mg dose(group 2). In group 1, serum oestradiol and inhibin-A concentrationsafter day 8 were lower than in the control cycles and the LHpeak was postponed by 7 days on average. Basal LH values increasedsignificantly on day 8 in both groups, while FSH values didnot change significantly compared with the control cycles. Asignificant increase in serum progesterone and cortisol valuesoccurred during the treatment only in group 1. Mid-luteal valuesof inhibin-A were significantly lower in cycles treated with100 mg mifepristone than in the control cycles. We concludethat the disruption of folliculogenesis by mifepristone cannotbe explained by a decrease in basal FSH concentrations duringthe critical period of follicle recruitment and selection. Itis possible that mifepristone exerts its effect at the levelof the ovary. It is also suggested that progesterone duringthe follicular phase of the cycle may participate in the controlof the self-priming action of GnRH on the pituitary.