SLEEP-ENDOCRINE EFFECTS OF MIFEPRISTONE AND MEGESTROL-ACETATE IN HEALTHY-MEN

Administration of steroid hormones was demonstrated to modulate the sl eep electroencephalogram (EEG) and sleep-associated hormonal secretion in specific ways. The present study was conducted to compare the effe cts of mifepristone (Mif), a mixed glucocorticoid (GR) and progesteron e receptor (PR) antagonist, and megestrol acetate (Meg), a PR agonist. Nine healthy men were pretreated with either placebo or 200 mg Mif or 320 mg Meg, or a combination of both. Changes in plasma adrenocortico tropic hormone (ACTH), cortisol, and growth hormone concentrations wer e registered every 30 min; sleep EEG recordings were obtained continuo usly. Administration of Mif increased the morning plasma ACTH and cort isol surges, whereas Meg had the opposite effect. Growth hormone secre tion was lowered by Mif pretreatment and enhanced by Meg. Simultaneous administration of both compounds led to largely compensated effects. The sleep EEG changes induced by Mif were a slight increase in the tim e awake and a delayed onset of slow-wave sleep. Meg led to a reduction of rapid-eye-movement sleep. Simultaneous administration of Mif and M eg showed a synergism in increasing time awake and shallow sleep: it t herefore may be concluded that the sleep EEG effects are mediated by a n interaction of GR and PR in unknown mechanisms.