Accelerated dissolution of luteal-endometrial integrity by the administration of antagonists of gonadotropin-releasing hormone and progesterone to late-luteal phase women

Abstract

Sequential blockade of gonadotropin-releasing hormone (GnRH) and progesterone (P) receptors by potent antagonists (Nal-Glu GnRH antagonist and RU486) was conducted in late-luteal phase women to develop a once-a-month birth control method by timed advancement of ongoing luteolysis and endometriolysis. Hormonal dynamics and timing of uterine bleeding during the antagonists' imposed luteal-follicular transition were compared with spontaneous (1st to 2nd) and recovery (2nd to 3rd) cycles in 10 normally cycling women. Serum luteinizing hormone (LH) and follicle-stimulating hormone levels declined (47 +/- 4.3% and 24 +/- 3.0%, respectively) by 24 hours after Nal-Glu injection, which accelerated the ongoing luteolytic process, as evidenced by more rapid declines of serum concentrations of estradiol, P, and ir-inhibin, as compared with the corresponding control cycle. This was accompanied by the prompt (16 +/- 3.2 hours after RU486) onset of a single episode of uterine bleeding, which was advanced by 2 days. Whereas the luteal phase length was foreshortened by 2 days, the subsequent follicular phase duration was prolonged by 2 days with a normal sequence of follicular maturation, LH surge, and luteal function during the recovery cycle. We conclude that the late-luteal sequential administration of antagonists of GnRH and P resulted in acceleration of the ongoing luteolytic and endometriolytic processes without functional alterations of the subsequent cycle.