Biomedical subjects

Doris Gruber

Publications and source records attributed to Doris Gruber.

6 recordsLinked to original sources

PubMed2005

Age-related cognitive decline in the menopause: effects of hormone replacement therapy on cognitive event-related potentials.

OBJECTIVE: Although epidemiological and clinical studies suggest that hormone replacement therapy (HRT) may protect against cognitive disorders and neurodegenerative diseases, the relation between estrogen and cognition in postmenopausal women remains controversial. METHODS: In a double-blind placebo-controlled, parallel group design study the effects of HRT with the estrogen-progestogen combination Presomen 1.25 compositum((R)) (1.25mg equine conjugated estrogens administered for 21 days plus the progestogen 5mg medrogeston given for 11 days) on event-related potentials (ERPs) in postmenopausal patients with age-related cognitive decline (DSM-IV code 780.9, ICD-10 code R 41.8) were investigated. After a pre-drug comparison with age-matched normal postmenopausal controls, 48 psychotropic drug-free patients aged 60 +/- 6 years were randomized to receive either placebo or verum for 4 months. ERPs were recorded before as well as on the 91-92 days of the study, which thus fell into the estrogen phase of the treatment during the fourth cycle. RESULTS: At baseline, patients showed a lengthening of P300 latency and an attenuation of P300 amplitudes as compared with normal controls. After HRT with Presomen, a significant shortening of P300 latency as compared with placebo was observed. CONCLUSIONS: The baseline P300 differences suggest that in the patient group the aging process was advanced, while after HRT with Presomen a significant improvement and normalization of information processing as indexed by P300 was observed.

Cognition↗

PubMed2004

Brain regions activated during an auditory discrimination task in insomniac postmenopausal patients before and after hormone replacement therapy: low-resolution brain electromagnetic tomography applied to event-related potentials.

Electrical sources of auditory event-related potentials (ERPs) determined by means of low-resolution brain electromagnetic tomography (LORETA) in 48 unmedicated insomniac postmenopausal patients aged between 46 and 67 years were compared with those obtained in 48 age-matched normal female controls. Subsequently, the patients were included in a double-blind, placebo-controlled, comparative, randomized 3-arm trial phase - Climodien 2/3 [estradiol valerate (EV) 2 mg + the progestin dienogest 3 mg] was compared with EV 2 mg and placebo - followed by an open-label phase in which all of them received Climodien 2/2 (EV 2 mg + dienogest 2 mg). The double-blind and the open-label phase lasted 2 months. ERPs were recorded from 19 EEG leads in a two-tone oddball paradigm and electrical sources of standard N1 and P2 as well as target N2 and P300 components were estimated. In both patients and controls, LORETA revealed an activation of the superior temporal gyrus [auditory cortex, Brodmann areas (BA) 41, 42, 22] for all four components. For standard P2, an additional activation was observed medially parietally in the precuneus (BA 7, 5). For target N2, also a medial frontal source (BA 9, 10, 32) was identified. Finally, for the target P300 component - in addition to the aforementioned sources - activations in the prefrontal cortex (BA 9, 10, 46, 47), the inferior parietal cortex (supramarginal gyrus, BA 40, 39) and the posterior cingulum (BA 31) were found. Thus, patients and controls did not differ in the structural processes engaged in these fundamental aspects of information processing. However, patients demonstrated significantly reduced source strength - for standard ERP components predominantly in the temporal lobe and for target components predominantly in the frontal lobe, indicating reduced energetic resources available for perceptual and cognitive demands of the discrimination task. While, as compared with placebo, estrogen alone had only minor effects on ERP source strength, Climodien generally increased the impressed current density at the ERP peak latencies, predominantly in the temporal lobe, indicating an increased stimulus-induced cortical arousal in the primary and higher-order auditory cortex. Specifically, Climodien enhanced P300 source strength in the left middle temporal gyrus and in the left superior frontal gyrus, brain regions that on the one hand have been shown to be affected by hormone therapy in positron emission tomography and functional magnetic resonance neuroimaging studies and that on the other hand are among those critical for encoding and memory processes.

Acoustic Stimulation↗

PubMed2004

Bazedoxifene (Wyeth).

Bazedoxifene is a tissue-specific selective estrogen receptor modulator being developed by Wyeth Pharmaceuticals (formerly Wyeth-Ayerst Laboratories) to be used alone for the prevention and treatment of osteoporosis in postmenopausal women and in combination with Premarin for menopausal symptoms. As of March and June 2004, worldwide phase III trials for bazedoxifene, and bazedoxifene in combination with Premarin, were ongoing.

Animals↗

PubMed2003

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.

Affect↗

PubMed2003

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.

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.

Aged↗

PubMed2002

Hormone replacement therapy and vigilance: double-blind, placebo-controlled EEG-mapping studies with an estrogen-progestogen combination (Climodien, Lafamme) versus estrogen alone in menopausal syndrome patients.

UNLABELLED: The aim of the double-blind, placebo-controlled study was to investigate the effects of a continuous combined estrogen-progestogen treatment (Climodien, Lafamme) as compared with estrogen alone on vigilance in insomniac postmenopausal syndrome patients, objectified by EEG mapping. METHODS: In a 3-arm, 2-month parallel group design phase, patients received a combination of estradiol valerate 2 mg and the novel progestogen dienogest 3 mg (Climodien 2/3) or estradiol valerate 2 mg alone or placebo. In a subsequent open-label phase, all patients received estradiol valerate 2 mg+dienogest 2 mg (Climodien 2/2). EEG mapping was carried out before and after the 2-month double-blind phase as well as after the 2-month open-label treatment. RESULTS: As compared with placebo, Climodien 2/3 induced a marked and highly significant increase in absolute power in all frequency bands, specifically in alpha-2 activity. Moreover, a significant increase in relative alpha-2 power, a decrease in relative delta and beta power as well as an acceleration of the dominant frequency and of the delta and alpha centroids suggested a marked improvement in vigilance. In contrast, under estradiol valerate 2 mg alone, only a slight augmentation of alpha and attenuation of relative delta and beta power occurred, suggesting only a slight vigilance improvement as compared with placebo. Thus, dienogest 2 mg increased the estrogen effect, which was also confirmed by a statistical evaluation of the differences between Climodien 2/3 and estradiol valerate alone (augmentation of alpha-2, attenuation of relative beta, acceleration of the dominant frequency). Moreover, Climodien 2/2 also markedly increased alpha-2 power, decreased relative beta-2 power and accelerated the alpha centroid. Finally, comparing Climodien 2/3 with Climodien 2/2, there was even a dose-efficacy relation. CONCLUSIONS: Estradiol valerate 2 mg improves vigilance slightly, thereby confirming previous findings. The additional administration of dienogest does not minimize the effect of estrogen, but on the contrary increases it, which makes the combination superior to both placebo and estradiol valerate alone. Vigilance improvement may be of great therapeutic benefit to menopausal syndrome patients at a time when increased adaptability is needed to adjust to increasing sexual, marital, occupational and social difficulties known to occur specifically in this period of life.

Aged↗