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

• Published in: Fertility and sterility Vol. 54; no. 5; p. 805
• Main Authors: Roseff, S J, Kettel, L M, Rivier, J, Burger, H G, Baulieu, E, Yen, S S
• Format: Journal Article
• Language: English
• Published: United States 01-11-1990
• Subjects: Adult; Corpus Luteum - drug effects; Corpus Luteum - physiology; Endometrium - drug effects; Endometrium - physiology; Estradiol - blood; Female; Gonadotropin-Releasing Hormone - administration & dosage; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropin-Releasing Hormone - antagonists & inhibitors; Gonadotropin-Releasing Hormone - pharmacology; Humans; Inhibins - blood; Luteal Phase - drug effects; Luteal Phase - physiology; Luteinizing Hormone - blood; Luteolysis - drug effects; Luteolysis - physiology; Mifepristone - administration & dosage; Mifepristone - pharmacology; Progesterone - antagonists & inhibitors; Progesterone - blood; Estrogens; Menstrual Cycle; Biology; Hormones; Research Methodology; Urogenital System; Ovary; Reproduction; Luteinizing Hormone > analysis; Clinical Research; Time Factors; Population; Physiology; Demographic Factors; Ru-486 > administraction and dosage; Progestational Hormones; Genitalia; Progesterone > analysis; Menstruation; Laboratory Examinations And Diagnoses; Gonadotropins; Examinations And Diagnoses; Hormone Antagonists > administraction and dosage; Endocrine System; Genitalia, Female; Gonadotropins, Pituitary; Luteolytic Effects > analysis; Estradiol > analysis; Follicle Stimulating Hormone > analysis; Corpus Luteum; Population Dynamics
• ISSN: 0015-0282
• DOI: 10.1016/S0015-0282(16)53936-3

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.