Effects of Hormone Therapy on Brain Volumes Changes of Postmenopausal Women Revealed by Optimally-Discriminative Voxel-Based Morphometry

Zhang, Tianhao; Casanova, Ramon; Resnick, Susan M.; Manson, Jo Ann E.; Baker, Laura D.; Padual, Claudia B.; Kuller, Lewis H.; Bryan, R. Nick; Espeland, Mark A.; Davatzikos, Christos

doi:10.1371/journal.pone.0150834

Cited by 29 publications

(32 citation statements)

References 67 publications

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“…There are recent reports of decreased frontal gray matter in MHT users versus nonusers, and several studies have focused on the hippocampus, with one showing a positive short‐term (i.e., 3‐month) treatment effect of relatively high doses of estradiol compared with low doses and placebo, but two others reporting null effects when comparing current, past, and nonusers . The pattern of findings could reflect MHT formulation (e.g., studies reporting null effects grouped users of estrogen‐only and combined therapies), or neural plasticity occurring around the MHT transition.…”

Section: Menopausal Hormone Therapymentioning

confidence: 99%

“…There are also conflicting reports of enlarged ventricular volumes, reflecting brain aging and cognitive decline, and increased white matter hyperintensities in MHT, with some studies finding effects and others not . Again, discrepancies may be due to transitional versus persisting effects of MHT, as studies reporting null results were based on longitudinal WHIMS‐MRI data collected several years after MHT cessation, and a key study reporting effects was a long‐term (i.e., 48‐month) randomized trial.…”

Section: Menopausal Hormone Therapymentioning

confidence: 99%

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Ovarian hormones: a long overlooked but critical contributor to cognitive brain structures and function

Beltz

Moser

2019

Annals of the New York Academy of Sciences

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Cognitive neuroscience research has traditionally overlooked half of the population. Arguing that variability in ovarian hormones confounds empirical findings, girls and women have been excluded from research for decades. But times are changing. This review summarizes historical trends that have led to a knowledge gap in the role of ovarian hormones in neuroscience, synthesizes recent findings on ovarian hormone contributions to cognitive brain structures and function, and highlights areas ripe for future work. This is accomplished by reviewing research that has leveraged natural experiments in humans across the life span that focus on puberty, the menstrual cycle, hormonal contraceptive use, menopause, and menopausal hormone therapy. Although findings must be considered in light of study designs (e.g., sample characteristics and group comparisons versus randomized crossover trials), across natural experiments there is consistent evidence for associations of estradiol with cortical thickness, especially in frontal regions, and hippocampal volumes, as well as with frontal regions during cognitive processing. There are also emerging investigations of resting state connectivity and progesterone along with exciting opportunities for future work, particularly concerning biopsychosocial moderators of and individual differences in effects in novel natural experiments. Thus, delineating complex ovarian hormone contributions to cognitive brain structures and function will advance neuroscience.

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Section: Menopausal Hormone Therapymentioning

confidence: 99%

Section: Menopausal Hormone Therapymentioning

confidence: 99%

Ovarian hormones: a long overlooked but critical contributor to cognitive brain structures and function

Beltz

Moser

2019

Annals of the New York Academy of Sciences

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“…Menopausal hormone therapy (HT; 0.625 mg/day conjugated equine estrogens (CEE) therapy alone (CEE-Alone) and in combination with 2.5 mg/day medroxyprogesterone acetate (CEE + MPA)) has recently been shown to produce significant Gray Matter (GM) losses compared to the placebo groups in the anterior cingulate and the adjacent medial frontal gyrus, and the orbitofrontal cortex and risk for cognitive impairment and dementia in older women [255]. …”

Section: Mechanisms Of Actions Of Estrogenic Endocrine Disruptors mentioning

confidence: 99%

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

Preciados

Yoo

Roy

2016

IJMS

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During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1) signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2) and NRF1. Some of these genes are involved with brain diseases, such as Alzheimer’s Disease (AD), Parkinson’s Disease, Huntington’s Disease, Amyotrophic Lateral Sclerosis, Autism Spectrum Disorder, and Brain Neoplasms. For example, the search of enriched pathways showed that top ten E2 interacting genes in AD—APOE, APP, ATP5A1, CALM1, CASP3, GSK3B, IL1B, MAPT, PSEN2 and TNF—underlie the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) AD pathway. With AD, the six E2-responsive genes are NRF1 target genes: APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1. These genes are also responsive to the following EEDs: ethinyl estradiol (APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1), BPA (APBB2, EIF2S1, ENO1, MAPT, and PAXIP1), dibutyl phthalate (DPYSL2, EIF2S1, and ENO1), diethylhexyl phthalate (DPYSL2 and MAPT). To validate findings from Comparative Toxicogenomics Database (CTD) curated data, we used Bayesian network (BN) analysis on microarray data of AD patients. We observed that both gender and NRF1 were associated with AD. The female NRF1 gene network is completely ...

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“…There were 23 more dementia cases per 10 000 person-years in the CEE plus progestin arm than in the placebo group (hazard ratio (HR) 2.1; 95% CI 1.2-3.5), and 12 more cases per 10 000 person-years in the CEE-alone arm (HR 1.5; 95% CI 0.8-2.7). The WHIMS-MRI ancillary study looked at structural changes in the brain of the WHI study participants 10 . Results actually were in line with the clinical data since they demonstrated that women assigned to HT had significant losses of gray matter compared to the placebo groups in several brain areas, while there were no regions where HT was significantly associated with larger volumes compared to placebo.…”

mentioning

confidence: 99%

Alzheimer's disease, menopause and the impact of the estrogenic environment

Pines

2016

Climacteric

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Decades ago, postmenopausal hormone replacement was considered the panacea for midlife women. Prevention of the age-related cognitive decline was among the top alleged benefits of this therapy. However, the data from the Women's Health Initiative Memory Study (WHI-WHIMS) study showed the opposite, indicating worsening of several cognitive domains in hormone users. Since WHIMS recruited women who were 65 years or older, it became crucial to investigate the effects of hormone therapy in the early menopause as well. Recent studies, such as WHIMS-Young, the Kronos Early Estrogen Prevention Study and the Early versus Late Intervention Trial with Estradiol targeted the younger women, and indeed showed that hormone therapy may have positive cognitive outcomes in this age group. Whether or not hormone therapy has an effect on already demented women remains to be further explored, as data are scarce.

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Effects of Hormone Therapy on Brain Volumes Changes of Postmenopausal Women Revealed by Optimally-Discriminative Voxel-Based Morphometry

Cited by 29 publications

References 67 publications

Ovarian hormones: a long overlooked but critical contributor to cognitive brain structures and function

Ovarian hormones: a long overlooked but critical contributor to cognitive brain structures and function

Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases

Alzheimer's disease, menopause and the impact of the estrogenic environment

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