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 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.
Stratton
P
P
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.
Hartog
B
B
Hajizadeh
N
N
Piquion
J
J
Sutherland
D
D
Merino
M
M
Lee
Y J
YJ
Nieman
L K
LK
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
D003283:Contraceptives, Postcoital, Synthetic; D009649:Norpregnadienes; D004958:Estradiol; C094854:ulipristal; D007986:Luteinizing Hormone