Disruption of follicular maturation and delay of ovulation after administration of the antiprogesterone RU486.
To investigate the role of progesterone in the follicular phase, we examined the effects of RU486 in eight normal cycling women studied with daily and frequent blood sampling (every 10 min for 10 h) during three menstrual cycles (control-treatment-recovery). RU486 (3 mg/kg, orally) was administered for 3 consecutive days after ultrasound documentation of a dominant follicle. In six of the eight women, RU486 was given after emergence of the dominant follicle, while in two women, RU486 was initiated during the preovulatory period when estradiol levels had exceeded 917 pmol/L. In the six women given RU486 after emergence of the dominant follicle, RU486 significantly prolonged the follicular phase duration from 15.6 +/- 1.9 (+/- SD) to 28.6 +/- 9.3 days (P less than 0.01) and extended the treatment cycle length to 42.3 +/- 9.1 (+/- SD) days (P less than 0.01). During RU486 treatment, mean serum estradiol levels decreased from 385 +/- 43 to 228 +/- 28 pmol/L (P less than 0.01), while LH, FSH, ACTH, cortisol, and progesterone levels changed little. LH pulse frequency and amplitude on the last day of RU486 administration did not differ from control values. Collapse of the dominant follicle was evident on ultrasound after RU486 administration and was not accompanied by uterine bleeding. In the two women treated during the preovulatory period, the follicular phase was not prolonged, and RU486 failed to delay the onset of the LH surge. Our findings indicate that RU486 treatment during the follicular phase interrupts normal follicular development, resulting in a delay of ovulation and a reinitiation of follicular recruitment.
Liu
J H
JH
Department of Reproductive Medicine, School of Medicine, University of California-San Diego, La Jolla 92093.
Garzo
G
G
Morris
S
S
Stuenkel
C
C
Ulmann
A
A
Yen
S S
SS
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000818:Animals; D004958:Estradiol / Q000097:blood; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005498:Follicular Phase / Q000187:drug effects*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008252:Macaca fascicularis; D015735:Mifepristone; D010060:Ovulation / Q000187:drug effects*; D011374:Progesterone / Q000037:antagonists & inhibitors* / Q000097:blood
D004963:Estrenes; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone