Effect of daily low dose mifepristone on the ovarian cycle and on dynamics of follicle growth.
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.


METHODS
Six healthy female volunteers were given 2mg mifepristone daily for 30 days following an ovulatory control cycle.


METHODS
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.


CONCLUSIONS
These findings add further evidence to support the contraceptive potential of mifepristone through effects on follicular development and on the menstrual cycle.
Cameron
S T
ST
Department of Obstetrics and Gynaecology, University of Edinburgh, UK.
Thong
K J
KJ
Baird
D T
DT
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage* / Q000494:pharmacology; D003864:Depression, Chemical; D004334:Drug Administration Schedule; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D015735:Mifepristone / Q000008:administration & dosage* / Q000494:pharmacology; D006080:Ovarian Follicle / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D010060:Ovulation / Q000187:drug effects* / Q000502:physiology; D014463:Ultrasonography
D003280:Contraceptives, Oral, Synthetic; D015735:Mifepristone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006854:Hydrocortisone