FOLLICLE-STIMULATING HORMONE-GRANULOSA CELL AXIS INVOLVEMENT IN THE ANTIFOLLICULOTROPHIC EFFECT OF LOW-DOSE MIFEPRISTONE (RU486)

This study was designed to assess the involvement of follicle stimulat ing hormone (FSH)-granulosa and luteinizing hormone (LH)-theca axes in the antifolliculotrophic effect of mifepristone. Plasma gonadotrophin s, including plasma LH bioactivity and pulsatility, oestradiol, testos terone and inhibin concentrations, and follicular growth were monitore d in volunteer women treated with placebo or mifepristone in two conse cutive cycles. Mifepristone was given either as a single dose of 5 mg (n = 7) when the leading follicle had reached a diameter between 12 an d 14 mm, or as a multiple dose of 5 mg/day for 3 days, beginning when the leading follicle had reached a diameter between 14 and 16 mm (n = 5) or between 6 and 11 mm (n = 5), Following the single dose of mifepr istone, follicular growth and the accompanying increase in plasma oest radiol were arrested at 12 and 36 h respectively without changes in go nadotrophin or testosterone serum concentrations. The 3 day regimen ar rested follicular growth and oestradiol rise and decreased plasma inhi bin concentrations when follicles were larger than 12 mm at the onset of treatment. These results indicate that the antifolliculotrophic act ion of mifepristone is associated with a selective compromise of the F SH-granulosa axis of dominant follicles that have passed a critical st age of growth.