Antiprogestin treatment decreases midluteal luteinizing hormone pulse amplitude and primarily exerts a pituitary inhibition

Abstract

Mifepristone (RU 486), a synthetic steroid with antiprogesterone receptor activity, was given with and without naloxone hydrochloride to six women in the midluteal phase to investigate the role of progesterone in the modulation of endogenous opioid activity and the secretion of luteinizing hormone and cortisol. Subjects were evaluated during four sequential monthly admissions during which multiple blood samples were obtained every 15 minutes for 8 hours. Patients were studied during a baseline cycle, after administration of RU 486 alone (100 mg /day), naloxone with RU 486, and naloxone alone. After administration of RU 486 there was a significant decline in total luteinizing hormone secretion (p<0.01) and luteinizing hormone pulse amplitude (p<0.05), but compared with baseline there was no significant change in luteinizing hormone pulse frequency. After infusion of naloxone there was a significant increase in mean luteinizing hormone values (p<0.05) and luteinizing hormone pulse frequency (p<0.01) but no change in pulse amplitude. There was no significant difference in mean luteinizing hormone values or luteinizing hormone pulse amplitude and frequency between administration of RU 486 and naloxone plus RU 486. Administration of naloxone alone, RU 486 alone, and RU 486 plus naloxone caused a significant increase in cortisol as compared with baseline cycles (p<0.05). These data further support the notion that progesterone is important in the control of luteinizing hormone secretion and suggest that progesterone may primarily influence luteinizing hormone pulse amplitude and pituitary release of luteinizing hormone during the luteal phase.