The purpose of this project is to understand better the development of the endometrium and oocyte in women and to investigate the role of gonadal steroids in these processes. Efforts during this reporting period characterized the biologic action of the antiprogestin CDB-2914, showing it to inhibit follicular development when given to women in the follicular phase when the dominant follicle is present. Results in 45 women show a prolongation of days from dosing to collapse of the dominant follicle. All but three women at placebo (n = 1) and 10 mg (n = 2) ovulated within 1 week of treatment, while those at 50 and 100 mg ovulated more than a week after treatment. After placebo or 10 mg, the lead follicle collapsed within 3 days of the LH surge. At 50 and 100 mg, the LH surge occurred more than 3 days before follicular collapse in 4 of 11 and 6 of 10 women respectively (p < 0.0001). There was also a dose-dependent change in lead follicle amd some women with a new lead follicle reported 2 LH surges. 3 women at 100 mg had luteinized unruptured follicles (LUF) and had elevated progesterone levels before the follicle was completely filled in, suggesting early luteinization of the follicle. Estradiol production was suppressed in a dose dependent fashion in the 4 days after treatment and before collapse. There was a significant increase in the number of delayed endometrial biopsies by the Noyes? criteria in all groups of women taking CDB 2914, compared to the placebo group. Despite the delay in ovulation at the higher doses, there was minimal lengthening of the treatment cycle, and any effect on menstrual cycle length was limited to the treatment cycle.
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