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Human Reproduction, Vol. 15, No. 5, 1092-1099, May 2000
© 2000 European Society of Human Reproduction and Embryology

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

Pamela Stratton1,6, Beth Hartog2, Negin Hajizadeh1, Johann Piquion1, Dorett Sutherland3, Maria Merino4, Young Jack Lee5 and Lynnette K. Nieman1

1 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, 2 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, George Washington University Medical Center, Washington DC, 3 Department of Nursing, Warren Grant Magnusen Clinical Center, 4 Surgical Pathology, National Cancer Institute, National Institutes of Health, and 5 Division of Epidemiology, Statistics, and Prevention, National Institute of Child Health and Human Development, Bethesda, MD 20892–1583, USA

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.

Key words: antiprogestin/CDB-2914/endometrium/follicle

6 To whom correspondence should be addressed


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