Effects of hormone replacement therapy on perceptual and cognitive event-related potentials in menopausal insomnia.
The influence of a combined estrogen-progestin regimen (Climodien, Lafamme) on auditory event-related potentials (ERPs) was investigated in a double-blind, placebo-controlled, comparative, randomized 3-arm trial phase (Climodien 2/3=estradiol valerate 2 mg+the progestin dienogest 3 mg, EV=estradiol valerate 2 mg, and placebo), followed by an open-label phase in which all patients received Climodien 2/2 (estradiol valerate 2 mg+dienogest 2 mg). Both the double-blind and the open-label phase lasted 2 months. ERPs were recorded from 19 EEG leads in a two-tone odd-ball paradigm in 49 patients aged between 46 and 67 yr with the diagnosis of insomnia (G 47.0) related to postmenopausal syndrome (N 95.1). Climodien reduced standard N1 and target P300 latencies as compared to placebo, while EV did not affect N1 latency but similarly reduced P300 latency. Climodien increased N1, P2 and P300 amplitudes dose-dependently, predominantly at frontal leads. Estrogen alone had only minor effects on ERP amplitudes. The shortening of standard N1 latency and enhancement of N1 and P2 amplitudes indicates a positive effect of Climodien on perceptual processing, most likely due to vigilance improvements also observed in EEG mapping. Concerning target P300, it seems that estradiol is responsible for the improvement in stimulus evaluation time, as reflected by the shortening of the peak latency, while dienogest seems to account for the improvement in cognitive information processing capacity, whereby 3 mg induced a more pronounced augmentation of P300 amplitudes than 2 mg. Based on the spatial distribution of this increase, it can be speculated that Climodien mainly affects the more frontally distributed P3a subcomponent, which is associated with attention and orientation. Furthermore, the observed changes in ERP-components are consistent with recent studies showing significant positive effects of hormone replacement therapy on cholinergic functions. Thus, Climodien seems to be of interest in preventing cognitive decline and treating cognitive disorders in postmenopausal women. Indeed, there is increasing evidence of beneficial effects of estrogen in dementia. Our present findings suggest that the estrogen effects may be augmented by dienogest.
Anderer
Peter
P
Department of Psychiatry, University of Vienna, Währinger Gürtel 18-20, Austria. peter.anderer@akh-wien.ac.at
Semlitsch
Heribert V
HV
Saletu
Bernd
B
Saletu-Zyhlarz
Gerda
G
Gruber
Doris
D
Metka
Markus
M
Huber
Johannes
J
Gräser
Thomas
T
Oettel
Michael
M
D000339:Affect; D000368:Aged; D004311:Double-Blind Method; D004338:Drug Combinations; D004594:Electrophysiology; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018913:Event-Related Potentials, P300 / Q000187:drug effects*; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D008875:Middle Aged; D009277:Nandrolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009483:Neuropsychological Tests; D017698:Postmenopause / Q000187:drug effects* / Q000502:physiology; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000494:pharmacology*; D011930:Reaction Time; D007319:Sleep Initiation and Maintenance Disorders / Q000503:physiopathology*
D004338:Drug Combinations; D045167:Progesterone Congeners; C454300:estradiol valerate-dienogest; C023635:dienogest; D004958:Estradiol; D009277:Nandrolone