Hippocampal volumes are larger in postmenopausal women using estrogen therapy compared to past users, never users and men: a possible window of opportunity effect.
ABSTRACT Considerable evidence suggests that estrogen can have neuroprotective effects. However, recent results raised important questions regarding the conditions under which hormone therapy (HT) following menopause can be beneficial. It has been suggested that variables such as time of initiation and duration of HT use are of critical importance for beneficial cognitive effects to be observed. The aim of the present study was to investigate the potential neuroprotective effects of estrogens in aging on brain regions with high levels of estrogen receptors, namely the hippocampus (HC) and the amygdala (AG). In order to better characterize the punctual and long-term effects of estrogens, we tested postmenopausal women currently using estrogen therapy alone (ET), past HT users, never users, and men. Age at menses, age at menopause, HT duration and age were included as covariates in the analysis. Results demonstrate that women using ET had larger left and right HC volumes compared to men, and larger right HC volumes compared to past users and never users. Importantly, we found a significant negative relationship between ET duration and HC volume in this group. The observed effects were region-specific since no significant differences could be observed for the AG. In summary, these findings support a treatment duration dependent neuroprotective role of estrogen on HC volume in aging.
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ABSTRACT: Findings from clinical studies in postmenopausal women with late initiation of hormone replacement therapy (HRT) that test whether HRT protects cognitive functions in women are inconsistent. The aim of this study was to investigate the effects of HRT on brain metabolite ratios when initiated in the early postmenopausal period (critical window). Proton magnetic resonance spectrometry (1H MRS) was performed in 4 brain regions of 47 healthy postmenopausal women (21 received HRT, 26 did not). The subjects were aged between 45 and 65 years. The duration of HRT ranged from 1 to 12 years (mean: 6.3 years). The duration of menopause was 2-12 years (mean: 6.1 years) for HRT users and 1-20 years (mean: 7.8 years) for non-HRT users. Metabolite ratios [N-acetyl aspartate/choline (NAA/Cho), NAA/creatine (Cr), and Cho/Cr] were evaluated. Cho/Cr ratios were significantly increased and NAA/Cho ratios significantly decreased in all 4 regions in the HRT user group compared to the other group after elimination of the effects of age and menopause duration. Regression analysis revealed an association only between NAA/Cho and duration of menopause. HRT-related changes in metabolite ratios are found in all brain regions. Decreased NAA/Cho and increased Cho/Cr levels do not support the neuroprotective role of HRT in the critical window.Turkish Journal of Medical Sciences 01/2014; 44(5):853-61. · 0.84 Impact Factor
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ABSTRACT: The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. The present review summarizes the findings of thirty-five studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri- and postmenopausal women treated with estrogen, or estrogen-progestagen replacement therapy. Seven studies using gonadotropin-releasing hormone agonist intervention as a model of hormonal withdrawal are also included. Cognitive paradigms are employed by the majority of studies evaluating the effect of unopposed estrogen or estrogen-progestagen treatment on peri- and postmenopausal women's brain. In randomized-controlled trials, estrogen treatment enhances activation of fronto-cingulate regions during cognitive functioning, though in many cases no difference in cognitive performance was present. Progestagens seems to counteract the effects of estrogens. Findings on cognitive functioning during acute ovarian hormone withdrawal suggest a decrease in activation of the left inferior frontal gyrus, thus essentially corroborating the findings in postmenopausal women. Studies of the cholinergic and serotonergic systems indicate these systems as biological mediators of hormonal influences on the brain. More, hormonal replacement appears to increase cerebral blood flow in several cortical regions. On the other hand, studies on emotion processing in postmenopausal women are lacking. These results call for well-powered randomized-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal variations on the brain.Frontiers in neuroscience. 01/2014; 8:388.
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ABSTRACT: To determine whether smaller brain volumes in older women who had completed Women's Health Initiative (WHI)-assigned conjugated equine estrogen-based hormone therapy (HT), reported by WHI Memory Study (WHIMS)-MRI, correspond to a continuing increased rate of atrophy an average of 6.1 to 7.7 years later in WHIMS-MRI2. A total of 1,230 WHI participants were contacted: 797 (64.8%) consented, and 729 (59%) were rescanned an average of 4.7 years after the initial MRI scan. Mean annual rates of change in total brain volume, the primary outcome, and rates of change in ischemic lesion volumes, the secondary outcome, were compared between treatment groups using mixed-effect models with adjustment for trial, clinical site, age, intracranial volumes, and time between MRI measures. Total brain volume decreased an average of 3.22 cm(3)/y in the active arm and 3.07 cm(3)/y in the placebo arm (p = 0.53). Total ischemic lesion volumes increased in both arms at a rate of 0.12 cm(3)/y (p = 0.88). Conjugated equine estrogen-based postmenopausal HT, previously assigned at WHI baseline, did not affect rates of decline in brain volumes or increases in brain lesion volumes during the 4.7 years between the initial and follow-up WHIMS-MRI studies. Smaller frontal lobe volumes were observed as persistent group differences among women assigned to active HT compared with placebo. Women with a history of cardiovascular disease treated with active HT, compared with placebo, had higher rates of accumulation in white matter lesion volume and total brain lesion volume. Further study may elucidate mechanisms that explain these findings.Neurology 02/2014; 82(5):427-34. · 8.30 Impact Factor