title: A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women.
abstract: Previous studies in women have shown that the antiprogestin mifepristone delays 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-four normally cycling, healthy women recorded urine LH and vaginal bleeding during pre-treatment, treatment, and post-treatment cycles. At a lead follicle 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 obtained until follicular collapse; an endometrial biopsy was obtained 5-7 days later. Single doses of CDB-2914 were well tolerated. Mid-follicular CDB-2914 suppressed lead follicle growth, causing a dose-dependent delay in folliculogenesis and suppression of plasma oestradiol. At higher doses, a new lead follicle was often recruited. Although luteinized unruptured follicles were observed at the 100 mg dose, all women had follicular collapse. There was a significant delay in endometrial maturation after CDB-2914 at all doses. 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 without major effects on menstrual cyclicity and may have therapeutic utility.
authors.affiliation: Pedriatric and Reproductive Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10 Room 9D42, 10 Center Dr. MSC 1583, Bethesda, MD 20892-1583, USA.
authors.forename: P
authors.initials: P
authors.lastname: Stratton
authors.forename: B
authors.initials: B
authors.lastname: Hartog
authors.forename: N
authors.initials: N
authors.lastname: Hajizadeh
authors.forename: J
authors.initials: J
authors.lastname: Piquion
authors.forename: D
authors.initials: D
authors.lastname: Sutherland
authors.forename: M
authors.initials: M
authors.lastname: Merino
authors.forename: Y J
authors.initials: YJ
authors.lastname: Lee
authors.forename: L K
authors.initials: LK
authors.lastname: Nieman
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002454:Cell Differentiation / Q000187:drug effects; D003283:Contraceptives, Postcoital, Synthetic / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008597:Menstrual Cycle / Q000187:drug effects* / Q000502:physiology; D009649:Norpregnadienes / Q000494:pharmacology*; D010048:Ovarian Cysts; D006080:Ovarian Follicle / Q000187:drug effects*; D010060:Ovulation / Q000187:drug effects
chemical_list: D003283:Contraceptives, Postcoital, Synthetic; D009649:Norpregnadienes; D004958:Estradiol; C094854:ulipristal; D007986:Luteinizing Hormone