Background and objective: The antiprogestin mifepristone has been shown to disrupt folliculogenesis and endometrial maturation and, therefore, has the potential to be used as a novel form of contraception. The purpose of this study was to investigate further the effects of daily administration of a low dose of mifepristone (2mg) on the ovarian cycle and on the dynamics of follicle growth.
Subjects: Six healthy female volunteers were given 2mg mifepristone daily for 30 days following an ovulatory control cycle.
Measurements: Follicle growth was monitored with transvaginal ultrasonography and hormonal measurements in blood and urine were used to monitor effects on the ovarian cycle. In addition, concentrations of cortisol and ACTH in serum were measured to assess the effects of mifepristone on the pituitary-adrenal axis.
Results: Treatment with mifepristone retarded the follicular growth rate in all women (P = 0.01). Ovulation was inhibited in 4 of 6 subjects and appeared to be mediated through an effect on the hypothalamo-pituitary axis, as no surge of FSH or LH occurred. In these subjects the dominant follicle continued to grow and developed into a persistent follicle. In two cases the persistent follicle remained functional and ovulation occurred soon after stopping treatment. In the remaining two subjects, the dominant follicle developed into a non-functioning cyst ( > 30 mm) which persisted for one month after the end of the post-treatment cycle. In the two subjects who ovulated, the LH surge was delayed by 6 and 7 days but was followed by a luteal phase of normal length. There was no significant change in the concentration of ACTH or cortisol suggesting that treatment with mifepristone in this dose has little if any effect on the pituitary-adrenal axis.
Conclusion: These findings add further evidence to support the contraceptive potential of mifepristone through effects on follicular development and on the menstrual cycle.
PIP: The Centre for Reproductive Biology at the University of Edinburgh, Scotland, recruited six healthy, regularly menstruating women aged 29-36 to a study designed to determine the effects of daily administration of 2 mg mifepristone on the dynamics of follicle growth. The women took a placebo every day during the first menstrual cycle, mifepristone every day, and then a placebo daily for the follow-up cycle. Transvaginal ultrasonography monitored follicle growth. Hormone measurements in the blood and urine as well as pelvic ultrasound monitored the activity of the pituitary-ovarian axis. During the control cycles, all the women had normal ovulation. During the treatment cycle, three patterns of follicle growth emerged: delayed ovulation (2 cases), persistent functional follicle (2 cases), and persistent non-functional cyst (2 cases). Four women did not ovulate during the treatment cycle. In these women, there was no surge of follicle stimulating hormone (FSH) or luteinizing hormone (LH). The dominant follicle still grew and became a persistent follicle. In two of these women, ovulation occurred soon after discontinuation of mifepristone. In the other two women, the dominant follicle became a non-functional cyst of greater than 30 mm in size, which remained for one month after the end of the last control cycle. Mifepristone slowed follicular growth in all women by 5.3 days on average (p = 0.01). It also slowed endometrial growth by 4 days on average (p = 0.04). At the end of both treatment and control cycles, however, the thickness of the endometrium was essentially the same. In the two women who did ovulate, the LH surge took place 6-7 days later than the control cycle, but the length of subsequent luteal phase was normal. Since there was no sizable change in the level of ACTH or cortisol, mifepristone at this low dose has limited influence on the pituitary-adrenal axis. These findings indicate that daily administration of 2 mg mifepristone does not consistently suppress ovulation.