Objective: Our objective was to determine if a progesterone antagonist might interdict the development of a secretory endometrium.
Study design: Eleven normally cycling women not at risk for pregnancy received RU 486 (1 mg/day orally) or placebo throughout one menstrual cycle in a randomized, double-blind, crossover fashion. Estradiol, progesterone, and placental protein 14 were measured every 3 days; luteinizing hormone was measured until the midcycle surge was detected. An endometrial biopsy was performed on luteal phase day 7 to 9 and interpreted with Noyes' criteria. Differences between treatment groups were analyzed by the Student t test.
Results: RU 486 delayed ovulation, retarded endometrial maturation, and reduced peak levels of placental protein 14 without affecting gonadal steroid production. The abnormalities in endometrial morphology and function are similar to those seen in infertile women with luteal phase defects.
Conclusion: We hypothesize that this regimen of antiprogestin administration may prevent implantation and offer a novel strategy for fertility control.
PIP: A small clinical study has provided preliminary evidence that a daily dose of 1 mg of RU-486 produces disruption of the morphology and function of the endometrium while preserving steroidogenesis, ovulation, and timing of the cycle. Enrolled in the study were 11 nonpregnant volunteers with regular menstrual cycles who received either RU-486 or a placebo during 2 treatment cycles in a randomized, crossover fashion. RU-486 delayed the midcycle luteinizing hormone surge and prolonged the follicular phase by 1-11 days in the 9 subjects included in the final analysis but did not alter the duration of the luteal phase. The mean length of the entire cycle increased an average of 6 days in RU-486 recipients. RU-486 also caused follicular phase estradiol and luteal phase progesterone concentrations to peak later compared with the placebo group. 6 of the 10 women who ovulated during RU-486 administration had delayed endometrial morphologic characteristics; another exhibited dyssynchrony between glandular and stromal tissue. Additional evidence for the antiprogestin effect of RU-486 on the endometrium was provided by finding of significantly lower peak placental protein 14 concentrations in treated subjects. RU-486 produced no effect on premenstrual symptoms, libido, dysmenorrhea, electrolytes, liver and renal functions, and cell blood counts. The potential of a small daily dose of a progesterone antagonist such as RU-486 as a fertility control agent merits further study.