Endocrinologic Effects of the Antiprogesterone RU 486 in the Luteal Phase of Normal Women

Abstract

RU 486 is a new synthetic antiprogesterone with anti-glucocorticoid activity. This study was designed to assess the tolerance of a single oral dose of RU 486 in normal cycling women during the luteal phase and to assess its effect on bleeding, gonadotropin and steroid patterns. Either 200, 400, 600 or 800 mg of the compound was orally administered to groups of five women at 0800 hours, and blood was sampled over a 48 hour period. There were no untoward clinical effects. Menses were induced in all but one patient within three days after ingestion of RU 486. This bleeding occurred in association with high levels of estradiol and progesterone. There was a further bleeding episode at the time of the expected menses. Plasma levels of RU 486 were maximum between 1 and 4 hours and remained elevated for 48 hours, indicating a prolonged disappearance time. Significant increases in prolactin were noted between 4 and 10 hours. Luteinizing hormone and estradiol were unchanged with the two lower dosages, but there was a transient decrease after the 600 and 800 mg dosage. Cortisol remained unchanged except for a late rise at 24 and 48 hours after the 400 mg and 800 mg dosage. There were no changes in follicle stimulating hormone, progesterone or ACTH.

We conclude that RU 486 is well-tolerated as a single oral dose in normal women and causes induction of menses. It also produces a transient elevation in serum prolactin, a delayed elevation in cortisol, and in higher dosages a decrease in luteinizing hormone and estradiol.