title: Insomnia related to postmenopausal syndrome and hormone replacement therapy: sleep laboratory studies on baseline differences between patients and controls and double-blind, placebo-controlled investigations on the effects of a novel estrogen-progestogen combination (Climodien, Lafamme) versus estrogen alone.
abstract: Differences in sleep and awakening quality between 51 insomniac postmenopausal syndrome patients and normal controls were evaluated. In a subsequent double-blind, placebo-controlled, comparative, randomized, three-arm trial (Climodien 2/3 = estradiol valerate 2 mg + the progestogen dienogest 3 mg = regimen A, estradiol valerate 2 mg = regimen EV, and placebo = regimen P), the effects of 2 months of hormone replacement therapy were investigated, followed by a 2-month open-label phase in which all patients received Climodien 2/2 (EV 2 mg + dienogest 2 mg = regimen A*). Polysomnography at baseline demonstrated significantly deteriorated sleep initiation and maintenance, increased S1 and decreased S2 in patients. Subjective sleep and awakening quality, well-being, morning drive, wakefulness, memory and reaction time performance were deteriorated too. Treatment with both regimen A and regimen EV induced a moderate, although nonsignificant, improvement in the primary efficacy variable wakefulness during the total sleep period compared with baseline, while under placebo no changes occurred. Secondary efficacy variables concerning sleep initiation and maintenance, and sleep architecture showed similar findings. The apnea and apnea-hypopnea indices improved significantly under regimen A, compared with both baseline and placebo. Subjective sleep and awakening quality improved significantly after regimen A and EV compared with baseline, with the drug-induced changes being superior to those induced by placebo. In the open-label phase, subjective sleep quality improved further, significantly in the former regimen A group. Awakening quality, somatic complaints and morning thymopsyche did not yield any significant findings. Concerning morning noopsychic performance, memory improved significantly after regimen A compared with baseline, fine motor activity after regimen EV. Reaction time performance increased with all three compounds. In conclusion, Climodien significantly improved subjective sleep quality, the apnea and apnea-hypopnea indices of insomniac postmenopausal syndrome patients, while it only marginally improved variables concerning objective sleep and awakening quality.
authors.affiliation: Department of Psychiatry, University of Vienna, Vienna, Austria.
authors.forename: Gerda
authors.initials: G
authors.lastname: Saletu-Zyhlarz
authors.forename: Peter
authors.initials: P
authors.lastname: Anderer
authors.forename: Georg
authors.initials: G
authors.lastname: Gruber
authors.forename: Magdalena
authors.initials: M
authors.lastname: Mandl
authors.forename: Doris
authors.initials: D
authors.lastname: Gruber
authors.forename: Markus
authors.initials: M
authors.lastname: Metka
authors.forename: Johannes
authors.initials: J
authors.lastname: Huber
authors.forename: Michael
authors.initials: M
authors.lastname: Oettel
authors.forename: Thomas
authors.initials: T
authors.lastname: Gräser
authors.forename: Manal Hassan
authors.initials: MH
authors.lastname: Abu-Bakr
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Grätzhofer
authors.forename: Bernd
authors.initials: B
authors.lastname: Saletu
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D004338:Drug Combinations; D004958:Estradiol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D009277:Nandrolone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D017286:Polysomnography; D017698:Postmenopause / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D012720:Severity of Illness Index; D012891:Sleep Apnea Syndromes / Q000188:drug therapy; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000628:therapy*; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
chemical_list: D004338:Drug Combinations; C454300:estradiol valerate-dienogest; D004958:Estradiol; D009277:Nandrolone