Inhibition of folliculogenesis and ovulation by the antiprogesterone RU 486.

ABSTRACT

Healthy, regularly menstruating women were treated with the antiprogesterone RU 486, Mifepristone (Roussel-Uclaf, Romainville, France) during the follicular phase of the cycle. Three women were given 25 mg of RU 486 on days 1 to 14 of the cycle and five received 25 mg on days 1 to 21 of the cycle. Venous blood samples were collected three times per week during a control cycle and during one treatment cycle in each subject. Serum concentrations of estradiol (E2), progesterone (P), and RU 486 were determined by radioimmunoassays. No drug-related side effects and no spotting or bleeding during RU 486 treatment were observed. Menstrual bleeding was delayed by 8.7 +/- 3.8 days (mean +/- SD) after treatment over days 1 to 14 and by 12.6 +/- 3.2 days after treatment over days 1 to 21. During the treatment with RU 486, the serum concentrations of E2 remained low, indicating effective inhibition of folliculogenesis. After cessation of RU 486 treatment, serum E2 levels rose to similar values as in the control cycle, and subsequently serum P concentrations also reached ovulatory levels in six out of the eight volunteers. The results showed that the antiprogesterone RU 486 delayed folliculogenesis and luteinization even at low doses when given during the follicular phase of the menstrual cycle. It is speculated that this property of RU 486 could be utilized in the design of an estrogen-free combined oral contraceptives.

ABSTRACT

PIP The antiprogesterone RU 486 (mifepristone, Roussel-Uclaf, Romainville, France) was taken by 3 women for days 1-14 of the menstrual cycle, and by 5 women on days 1-21, at a low dose of 25 mg/day, to see whether it would affect ovulation. There is normally a brief progesterone peak before the LH surge that precedes ovulation. To monitor the cycle, women reported bleeding symptoms, and their serum estradiol, progesterone and RU 486 levels were assayed. There were no side effects or bleeding or spotting reported. Serum estradiol levels remained below those recorded in the control cycle, indicating that development of the follicle was inhibited. Estradiol levels rose to follicular phase levels after discontinuation of the drug. Menstruation was delayed by 6, 6 and 14 (mean 8.7) days in the women who took RU 486 for 14 days, and by 8, 12, 12, 13 and 18 days (mean 12.6) days in those who took it for 21 days. The subsequent luteal phase was of normal duration and progesterone level. Based on progesterone level, 2 treatment cycles were anovulatory. Serum RU 486 concentrations ranged from 200 to 1400 ng/ml. It is conceivable that an estrogen-free combined oral contraceptive could be developed based on this property of RU 486.