Hippocampal volumes are larger in postmenopausal women using estrogen therapy compared to past users, never users and men: A possible window of opportunity effect

ArticleinNeurobiology of aging 29(1):95-101 · February 2008with8 Reads
DOI: 10.1016/j.neurobiolaging.2006.09.001 · Source: PubMed
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.
    • "The hormone theory provides a useful framework for interpreting this finding. After the age of 30 years, estrogen decreases gradually in women [41] and results in a decline in well-being [42]. Decreased estrogen can also aggravate insomnia. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Poor sleep quality and depression negatively impact the health-related quality of life of patients with type 2 diabetes, but the combined effect of the two factors is unknown. This study aimed to assess the interactive effects of poor sleep quality and depression on the quality of life in patients with type 2 diabetes. Methods Patients with type 2 diabetes (n = 944) completed the Diabetes Specificity Quality of Life scale (DSQL) and questionnaires on sleep quality and depression. The products of poor sleep quality and depression were added to the logistic regression model to evaluate their multiplicative interactions, which were expressed as the relative excess risk of interaction (RERI), the attributable proportion (AP) of interaction, and the synergy index (S). Results Poor sleep quality and depressive symptoms both increased DSQL scores. The co-presence of poor sleep quality and depressive symptoms significantly reduced DSQL scores by a factor of 3.96 on biological interaction measures. The relative excess risk of interaction was 1.08. The combined effect of poor sleep quality and depressive symptoms was observed only in women. Conclusions Patients with both depressive symptoms and poor sleep quality are at an increased risk of reduction in diabetes-related quality of life, and this risk is particularly high for women due to the interaction effect. Clinicians should screen for and treat sleep difficulties and depressive symptoms in patients with type 2 diabetes.
    Full-text · Article · Dec 2016
    • "Further, we examined potential interactions with regard to age, sex, and severity of obesity, and aimed to control for manifesting comorbidities including hypertension, diabetes and intake of antihyperlipidemic medication (Biessels et al., 2008; Elias et al., 2005) in both adjusted and sensitivity statistical analyses, as for example, related medical treatment could have confounded the effects of BMI in older age (Beeri et al., 2008; Jennings and Zanstra, 2009; Nadkarni et al., 2015; Patrone et al., 2014). In addition, we sought to additionally control for various factors known to affect brain structure and cognition, including white matter hyperintensities (Wen et al., 2006), depression (Kirwan et al., 2008), smoking and education status (Garibotto et al., 2008; Karama et al., 2015), intake of estrogen supplements (Lord et al., 2008 ), as well as apolipoprotein E (APOE) e4 genotype (Wishart et al., 2006). We additionally evaluated if BMI indirectly affected cognitive performance through changes in regional GMV using simple mediation analyses, and if this effect was moderated by age. "
    [Show abstract] [Hide abstract] ABSTRACT: Midlife obesity has been associated with increased dementia risk, yet reports on brain structure and function are mixed. We therefore assessed the effects of body mass index (BMI) on gray matter volume (GMV) and cognition in a well-characterized sample of community-dwelled older adults. GMV was measured using 3T-neuroimaging in 617 participants (258 women, 60-80 years, BMI 17-41 kg/m2). Also, cognitive performance and various confounders including hypertension, diabetes and APOE-genotype were assessed. A higher BMI correlated significantly with lower GMV in multiple brain regions, including (pre)frontal, temporal, insular and occipital cortex, thalamus, putamen, amygdala and cerebellum, even after adjusting for confounders. Also, lower GMV in prefrontal and thalamic areas partially mediated negative effects of (1) higher BMI and (2) higher age on memory performance. We here showed that a higher BMI in older adults is associated with widespread gray matter alterations, irrespective of obesity-related co-morbidities and other confounders. Our results further indicate that a higher BMI induces structural alterations that translate into subtle impairments in memory performance in aging.
    Article · Jan 2016 · BMC Family Practice
    • "In contrast to these largely negative findings, two studies of menstrual fluctuations have suggested that gray matter volume in the right anterior hippocampus (Protopopescu et al., 2008) or right parahippocampal/ fusiform gyri (Pletzer et al., 2010 ) is greater in women during the higherestrogen , compared to lower-estrogen phase of the cycle. Similarly, two studies of post-menopausal women found associations between hormone replacement therapy (HRT) and larger right HCV (Eberling et al., 2003; Lord et al., 2008). However, these results could be explained by " healthy user bias, " a significant confound in many observational studies of HRT (Gleason et al., 2012), and they are also contradicted by another study (Raz et al., 2004b), which found that HCV in aging women was not related to HRT. "
    Full-text · Dataset · Sep 2015 · BMC Family Practice
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