Sleep after intranasal progesterone vs. zolpidem and placebo in postmenopausal women - A randomized, double-blind cross over study.

CONTEXT: The loss of progesterone during menopause is linked to sleep complaints of the affected women. Previously we demonstrated sleep promoting effects of oral progesterone replacement in postmenopausal women. The oral administration of progesterone, however, is compromised by individual differences in bioavailability and metabolism of the steroid. OBJECTIVE: We compared the sleep-endocrine effects after intranasal progesterone (MPP22), zolpidem and placebo in healthy postmenopausal women. DESIGN: This was a randomized double-blind cross-over study. SETTING: German monocentric study PARTICIPANTS: Participants were 12 healthy postmenopausal women. INTERVENTIONS: Subjects received in randomized order four treatments, 2 doses of intranasal progesterone (4.5 mg and 9 mg of MPP22), 10 mg of zolpidem and placebo. OUTCOME MEASURES: Main outcome were conventional and quantitative sleep-EEG variables. Secondary outcomes were the subjective sleep variables and the sleep related concentrations of cortisol, growth hormone (GH), melatonin and progesterone. RESULTS: Sleep promoting effects were found after the higher dosage of MPP22 and after zolpidem. Zolpidem prompted benzodiazepine-like effects on quantitative sleep EEG as expected, whereas no such changes were found after the two dosages of MP22. Nocturnal progesterone levels increased after 9.0 mg MPP22. No other changes of hormone secretion were found. CONCLUSIONS: Our study shows sleep promoting effects after intranasal progesterone. The spectral signature of intranasal progesterone did not resemble the sleep-EEG alterations induced by GABA active compounds. Progesterone levels were elevated after 9.0 mg MPP22. No other endocrine effects were observed.

Low doses of dexamethasone affect immune parameters in the absence of immunological stimulation.

Recent findings suggest an important role of subtle changes in the plasma levels of inflammatory cytokines within the brain-immune interplay. It is unclear how such changes are regulated in the absence of acute inflammatory or infectious stimuli. Endocrine systems are a good candidate, because innate immunity and the hypothalamo-pituitary-adrenal (HPA)-system are closely related: glucocorticoids have immunosuppressive properties and modulate cytokine release from stimulated mononuclear blood cells in vitro and the immune response in vivo, but it still remains unclear, whether they also modulate circulating cytokine levels in the absence of immunological stimuli. We measured the influence of 1.5 or 3.0 mg dexamethasone (DEX) per os at 09:00 or 21:00 hours on body temperature, cortisol plasma levels, differential white blood cell counts, and cytokine plasma levels in 40 healthy male volunteers using a double-blind, placebo-controlled study design. In addition to significant morning-evening differences in tympanic temperature and several immune parameters, we found that DEX-intake significantly increased tympanic temperature, decreased cortisol plasma levels, altered differential white blood cell counts and induced changes in unstimulated plasma cytokine levels. Whereas the levels of TNF-alpha and sTNF-R p75 were reduced, the levels of sTNF-R p55 increased after a transient decrease.

Neuroscience-driven discovery and development of sleep therapeutics.

Until recently, neuroscience has given sleep research and discovery of better treatments of sleep disturbances little attention, despite the fact that disturbed sleep has overwhelming impact on human health. Sleep is a complex phenomenon in which specific psychological, electrophysiological, neurochemical, endocrinological, immunological and genetic factors are involved. The brain as both the generator and main object of sleep is obviously of particular interest, which makes a neuroscience-driven view the most promising approach to evaluate clinical implications and applications of sleep research. Polysomnography as the gold standard of sleep research, complemented by brain imaging, neuroendocrine testing, genomics and other laboratory measures can help to create composite biomarkers that allow maximizing the effects of individualized therapies while minimizing adverse effects. Here we review the current state of the neuroscience of sleep, sleep disorders and sleep therapeutics and will give some leads to promote the discovery and development of sleep medicines that are better than those we have today.

Association of auditory hallucinations and anticonvulsant hypersensitivity syndrome with carbamazepine treatment. A case report.

Carbamazepine is effective in the treatment of acute mania and in the prevention of episodes in bipolar disorder, and it may also be useful in depression, impulse-control disorder and withdrawal from alcohol and benzodiazepine dependence. A potentially life-threatening side effect is the anticonvulsant hypersensitivity syndrome. Here, we describe a patient who developed severe auditory hallucinations followed by a distinct hypersensitivity syndrome most likely induced by carbamazepine treatment.