The Effect of 3‐Year Treatment with 0.25 mg/day of Micronized 17β‐Estradiol on Cognitive Function in Older Postmenopausal Women

Pefanco, Mary Ann; Kenny, Anne M.; Kaplan, Richard F.; Kuchel, George A.; Walsh, Stephen J.; Kleppinger, Alison; Prestwood, Karen M.

doi:10.1111/j.1532-5415.2007.01085.x

Cited by 42 publications

(31 citation statements)

References 41 publications

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“…Consistent with the redox-sensitivity of AKT, 4-OH-E2- or H2O2-induced NRF-1 phosphorylation was inhibited by the glutathione peroxidase mimic, ebselen. AKT activity depends on its phosphorylation, which is positively regulated by PI3K and negatively regulated by a class of protein phosphatases [52]. AKT controls translocation of NRF-1 to the nucleus, because translocation of NRF-1 to the nucleus does not occur in PTEN deficient cells.…”

Section: Discussionmentioning

confidence: 99%

“…Another finding from Resnick et al (2009), showed estrogen alone, as conjugated equine estrogen, did not improve cognitive functioning and lowered certain cognitive functions in women with prior hysterectomy [48]. Other studies have indicated that no visible improvement has been observed in using estrogen only treatments for cognitive function [49,50,51,52]. Other studies that administered estrogen only treatments to younger surgically menopausal women have shown benefits to memory [53,54], which may show an age-related effect of estrogen only treatments.…”

Section: Epidemiologic and Experimental Evidence Of Brain Health Dmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Epidemiologic and Experimental Evidence Of Brain Health Dmentioning

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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“…Studies examining estradiol therapy specifically initiated in older women (70+) have not shown significant benefit (Almeida et al, 2006; Buckwalter et al, 2004; Espeland et al, 2004; Pefanco et al, 2007; Yaffe et al, 2006), whereas studies of hormone treatment in women initiating at midlife or in the early postmenopausal period, tend to show improvement (MacLennan et al, 2006; Shaywitz et al, 2003; Stevens et al, 2005a; Stevens et al, 2005b). This has been formulated as the “critical period hypothesis” (Maki, 2005b; Pinkerton and Henderson, 2005; Sherwin, 2007) suggesting that there is a limited window of time to initiate hormone treatment for an undefined period after menopause if beneficial effects on brain function are to be seen (Singh et al, 2013).…”

Section: Implications and Discussionmentioning

confidence: 99%

Estrogen–cholinergic interactions: Implications for cognitive aging

Newhouse

Dumas

2015

Hormones and Behavior

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While many studies in humans have investigated the effects of estrogen and hormone therapy on cognition, potential neurobiological correlates of these effects have been less well studied. An important site of action for estrogen in the brain is the cholinergic system. Several decades of research support the critical role of CNS cholinergic systems in cognition in humans, particularly in learning and memory formation and attention. In humans, the cholinergic system has been implicated in many aspects of cognition including the partitioning of attentional resources, working memory, inhibition of irrelevant information, and improved performance on effort-demanding tasks. Studies support the hypothesis that estradiol helps to maintain aspects of attention and verbal and visual memory. Such cognitive domains are exactly those modulated by cholinergic systems and extensive basic and preclinical work over the past several decades has clearly shown that basal forebrain cholinergic systems are dependent on estradiol support for adequate functioning. This paper will review recent human studies from our laboratories and others that have extended preclinical research examining estrogen-cholinergic interactions to humans. Studies examined include estradiol and cholinergic antagonist reversal studies in normal older women, examinations of the neural representations of estrogen-cholinergic interactions using functional brain imaging, and studies of the ability of selective estrogen receptor modulators such as tamoxifen to interact with cholinergic-mediated cognitive performance. We also discuss the implications of these studies for the underlying hypotheses of cholinergic-estrogen interactions and cognitive aging, and indications for prophylactic and therapeutic potential that may exploit these effects.

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“…These observations indicate that ovarian hormones critically mediate depressive-like symptoms. It should be noted, however, that some clinical studies show no effects of estrogen replacement therapy on reversing depressive-like symptoms for postmenopausal women (Almeida et al, 2006; Goldstein et al, 2005; Martel et al, 2009; Morrison et al, 2004; Pefanco et al, 2007; Schmidt and Rubinow, 2002). …”

Section: MDmentioning

confidence: 99%

Sex-dependent mental illnesses and mitochondria

Shimamoto

Rappeneau

2017

Schizophrenia Research

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The prevalence of some mental illnesses, including major depression, anxiety-, trauma-, and stress-related disorders, some substance use disorders, and later onset of schizophrenia, is higher in women than men. While the higher prevalence in women could simply be explained by socioeconomic determinants, such as income, social status, or cultural background, extensive studies show sex differences in biological, pharmacokinetic, and pharmacological factors contribute to females’ vulnerability to these mental illnesses. In this review, we focus on estrogens, chronic stress, and neurotoxicity from behavioral, pharmacological, biological, and molecular perspectives to delineate the sex differences in these mental illnesses. Particularly, we investigate a possible role of mitochondrial function, including biosynthesis, bioenergetics, and signaling, on mediating the sex differences in psychiatric disorders.

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The Effect of 3‐Year Treatment with 0.25 mg/day of Micronized 17β‐Estradiol on Cognitive Function in Older Postmenopausal Women

Abstract: This small study, which had adequate power to detect change in some but not all domains of cognition tested, revealed that low-dose estrogen neither benefits nor harms cognitive function in older women after 3 years of treatment, but confirmation is needed from larger trials.

Cited by 42 publications

References 41 publications

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

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

Estrogen–cholinergic interactions: Implications for cognitive aging

Sex-dependent mental illnesses and mitochondria

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