A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women

Previous studies in women have shown that the antiprogestin mifepristone de lays or inhibits folliculogenesis. The purpose of this study was to explore whether a new analogue, CDB-2914, has similar effects on folliculogenesis, ovulation, or on subsequent luteal phase endometrial maturation. Forty-fou r normally cycling, healthy women recorded urine LH and vaginal bleeding du ring pre-treatment, treatment, and post-treatment cycles. At a lead follicl e diameter of 14-16 mm, a single oral dose (10, 50, 100 mg) of CDB-2914 or placebo was given, and daily ultrasound, oestradiol and progesterone were o btained until follicular collapse; an endometrial biopsy was obtained 5-7 d ays later. Single doses of CDB-2914 were well tolerated. Mid-follicular CDB -2914 suppressed lead follicle growth, causing a dose-dependent delay in fo lliculogenesis and suppression of plasma oestradiol. At higher doses, a new lead follicle was often recruited. Although luteinized unruptured follicle s were observed at the 100 mg dose, all women had follicular collapse. Ther e was a significant delay in endometrial maturation after CDB-2914 at all d oses. The treatment cycle was lengthened by 1-2 weeks in 30% at 100, 27% at 50 and 9% at 10 mg. CDB-2914 altered ovarian and endometrial physiology wi thout major effects on menstrual cyclicity and may have therapeutic utility .