Sleep-endocrine effects of mifepristone and megestrol acetate in healthy men

Abstract

Administration of steroid hormones was demonstrated to modulate the sleep electroencephalogram (EEG) and sleep-associated hormonal secretion in specific ways. The present study was conducted to compare the effects of mifepristone (Mif), a mixed glucocorticoid (GR) and progesterone 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 adrenocorticotropic hormone (ACTH), cortisol, and growth hormone concentrations were registered every 30 min; sleep EEG recordings were obtained continuously. Administration of Mif increased the morning plasma ACTH and cortisol surges, whereas Meg had the opposite effect. Growth hormone secretion 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 time awake and a delayed onset of slow-wave sleep. Meg led to a reduction of rapid-eye-movement sleep. Simultaneous administration of Mif and Meg showed a synergism in increasing time awake and shallow sleep: it therefore may be concluded that the sleep EEG effects are mediated by an interaction of GR and PR in unknown mechanisms.

Blocking Mineralocorticoid Receptors Impairs, Blocking Glucocorticoid Receptors Enhances Memory Retrieval in Humans

“…Similarly, consistent with previous findings (Wiedemann et al , 1998), the GR antagonist mifepristone increased morning rises in plasma cortisol and ACTH, resulting in higher concentrations of these hormones during the time of retrieval testing. In contrast, neither spironolactone nor mifepristone affected norepinephrine levels.…”

“…GR blockade likewise did not influence affect, attention or working memory. Sleep prior to retrieval testing was also comparable between the placebo and active agent conditions in both studies except that on the mifepristone condition subjects were longer awake and showed reduced time in REM sleep, replicating previous findings (Wiedemann et al , 1992, 1998). However, the size of the change was small and sleep disturbing effects like increased time awake or decreased REM sleep are expected to diminish rather than enhance executive functions like retrieval (Durmer and Dinges, 2005; Killgore, 2010) making it highly unlikely that these changes in sleep contributed to the improved retrieval performance during GR blockade.…”

Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

“…For instance, synthetic progestins reduced REM/paradoxical sleep (PS) [40] and our data showed that mifepristone decreased the duration of PS episodes in male rats [12]. This suggests that progesterone must be involved in REM/PS regulation and that it may play a functional role in regulating genital mechanisms in males.…”

Sleep, Hormones, and Circadian Rhythms throughout the Menstrual Cycle in Healthy Women and Women with Premenstrual Dysphoric Disorder

“…Specifically, progesterone, as well as its neuroactive metabolites, can affect sleep architecture, as was illustrated by the findings that exogenous progesterone [69] or megestrol acetate, a progesterone-receptor agonist [70], reduced REM sleep in male participants. Likewise, exogenous progesterone in rats reduced REM sleep while lengthening ROL [71].…”