The role of pre-ovulatory progesterone in the midcycle gonadotrophin surge, ovulation and subsequent luteal phase: studies with RU486 in rhesus monkeys.

Conflicting evidence exists on the possible physiological role of progesterone in the regulation of the midcycle surge of gonadotrophins during the normal primate menstrual cycle. We designed the present study based on the availability of a potent antiprogesterone, RU486, that acts by binding to the progesterone receptor without inducing progestational activity. Regularly cycling rhesus monkeys received daily administration of RU486, 10 mg orally (n = 8) or vehicle (n = 5) from the day of the menstrual cycle in which serum oestradiol was 130 pg/ml or more, and a laparoscopy revealed the presence of a dominant follicle. While vehicle administration did not affect the normal ovulatory pattern nor the hormonal milieu of the menstrual cycles, RU486 induced marked aberrations during the treated cycles. Delay of ovulation with a normal subsequent luteal phase was observed in three animals. Three animals remained anovulatory until the following cycle and two animals that ovulated on days 14 and 16 of the treated cycles had short luteal phases. Analysis of daily FSH, LH, oestradiol and progesterone revealed that the administration of RU486 disrupted the midcycle pattern of gonadotrophins by disrupting them after the surge was initiated. Oestradiol surges were not different from controls and in all animals the ascendant levels of progesterone were interrupted by the administration of the antiprogesterone. This study clearly shows that the pre-ovulatory administration of RU486, a potent antiprogesterone, alters pre-ovulatory gonadotrophin secretion, inducing different degrees of menstrual irregularities such as anovulation, delayed ovulations and short luteal phases.(ABSTRACT TRUNCATED AT 250 WORDS)