Effects of metyrapone on hypothalamic-pituitary-adrenal axis and sleep in women with post-traumatic stress disorder.
BACKGROUND
Metyrapone blocks cortisol synthesis which results in removal of negative feedback, a stimulation of hypothalamic corticotropin releasing factor (CRF) and a reduction in delta sleep. We previously reported a diminished delta sleep and hypothalamic-pituitary-adrenal (HPA) response to metyrapone in men with post-traumatic stress disorder (PTSD). In this study, we aimed to extend these findings to women.


METHODS
Three nights of polysomnography were obtained in 17 women with PTSD and 16 controls. On day 3, metyrapone was administered throughout the day up until bedtime. Plasma adrenocorticotropic hormone (ACTH), cortisol, and 11-deoxycortisol were obtained the morning following sleep recordings the day before and after metyrapone administration.


RESULTS
There were no significant between-group differences in hormone concentration and delta sleep at baseline. Relative to controls, women with PTSD had decreased ACTH and delta sleep responses to metyrapone. Decline in delta sleep was associated with the magnitude of increase in ACTH across groups.


CONCLUSIONS
Similar to our previous findings in men, the ACTH and sleep electroencephalogram response to metyrapone is attenuated in women with PTSD. These results are consistent with a model of downregulation of CRF receptors in an environment of chronically increased CRF activity or with enhanced negative feedback regulation in PTSD.
Otte
Christian
C
Department of Psychiatry, University of California, San Francisco, California, USA.
Lenoci
Maryann
M
Metzler
Thomas
T
Yehuda
Rachel
R
Marmar
Charles R
CR
Neylan
Thomas C
TC
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000704:Analysis of Variance; D003350:Cortodoxone / Q000097:blood; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008797:Metyrapone / Q000008:administration & dosage*; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D017286:Polysomnography; D012890:Sleep / Q000187:drug effects*; D013313:Stress Disorders, Post-Traumatic / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology
D004791:Enzyme Inhibitors; D000324:Adrenocorticotropic Hormone; D003350:Cortodoxone; D006854:Hydrocortisone; D008797:Metyrapone