The Effect of Estrogen Replacement Therapy on Alzheimer's Disease and Parkinson's Disease in Postmenopausal Women: A Meta-Analysis

Song, Yujia; Li, Shu-ran; Li, Xiaowan; Chen, Xi; Wei, Ze-Xu; Liu, Qingshan; Cheng, Yong

doi:10.3389/fnins.2020.00157

Cited by 120 publications

(107 citation statements)

References 49 publications

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“…However, other neuroimaging studies suggest a protective effect of hormone replacement therapy (HRT) on gray matter (Erickson et al, 2005), as well as white matter and ventricle size (Ha et al, 2007). Furthermore, a recent meta‐analysis suggests protective effects of estrogen replacement therapy on the risk of onset and/or development of AD and Parkinson Disease in postmenopausal women (Song et al, 2020). Emerging evidence indicates that oral contraceptives (OC), another source of exogenous estrogen, affect aspects of brain structure and function in young adults (reviewed by [Pletzer & Kerschbaum, 2014]), but despite their widespread use (Christin‐Maitre, 2013), the impact of OCs on brain aging is unknown.…”

Section: Introductionmentioning

confidence: 99%

Women's brain aging: Effects of sex‐hormone exposure, pregnancies, and genetic risk for Alzheimer's disease

Lange

Barth

Kaufmann

et al. 2020

Human Brain Mapping

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Sex hormones such as estrogen fluctuate across the female lifespan, with high levels during reproductive years and natural decline during the transition to menopause. Women's exposure to estrogen may influence their heightened risk of Alzheimer's disease (AD) relative to men, but little is known about how it affects normal brain aging. Recent findings from the UK Biobank demonstrate less apparent brain aging in women with a history of multiple childbirths, highlighting a potential link between sex-hormone exposure and brain aging. We investigated endogenous and exogenous sex-hormone exposure, genetic risk for AD, and neuroimaging-derived biomarkers for brain aging in 16,854 middle to older-aged women. The results showed that as opposed to parity, higher cumulative sex-hormone exposure was associated with more evident brain aging, indicating that i) high levels of cumulative exposure to sex-hormones may have adverse effects on the brain, and ii) beneficial effects of pregnancies on the female brain are not solely attributable to modulations in sexhormone exposure. In addition, for women using hormonal replacement therapy (HRT), starting treatment earlier was associated with less evident brain aging, but only in women with a genetic risk for AD. Genetic factors may thus contribute to how timing of HRT initiation influences women's brain aging trajectories.

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Section: Introductionmentioning

confidence: 99%

Women's brain aging: Effects of sex‐hormone exposure, pregnancies, and genetic risk for Alzheimer's disease

Lange

Barth

Kaufmann

et al. 2020

Human Brain Mapping

View full text Add to dashboard Cite

show abstract

“…In women, higher levels of sex-related hormones (such as estrogen) may be associated with increased risk for age-related neurodegenerative diseases such as AD 2 . On average, women above 40 years of age are at a greater risk of developing AD than age-matched men.…”

Section: Introductionmentioning

confidence: 99%

Exogenous Sex Hormone Effects on Brain Microstructure in Women: A diffusion MRI Study in the UK Biobank

Nabulsi¹,

Lawrence²,

Santhalingam³

et al. 2020

Preprint

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This study used advanced diffusion-weighted MRI (dMRI) to examine the association between exogenous sex-hormone exposure and the brain’s white matter aging trajectories in a large population-based sample of women. To investigate the effect of pre- and post-menopausal sex hormones on brain aging, cross-sectional brain dMRI data from the UK Biobank was analyzed using 3 diffusion models: conventional diffusion tensor imaging (DTI), the tensor distribution function (TDF), and neurite orientation dispersion and density imaging (NODDI). Mean skeletonized diffusivity measures were extracted and averaged across the whole brain, including fractional anisotropy, isotropic volume fraction, intracellular volume fraction and orientation dispersion index. We used general linear models and fractional polynomial regressions to characterize age-related trajectories in white matter measures following hormone therapy (HT) and oral contraceptive (OC) use in women (HT analysis: N=8,301; OC analysis: N=8,913). Sex hormone treatment (HT and OC) was statistically associated with the aging trends in white matter measures. Estrogen therapy alone appeared to exert a neuroprotective effect on age-related white matter processes, compared to HT containing both estrogen and progestin therapy – which was associated with accelerated aging-related processes in women. These results support the hypothesis that exogenous sex hormone exposure may impact white matter aging; white matter metrics may also be sensitive to sex hormone levels in women. Furthermore, we discuss the necessity to test alternative models for lifespan trajectories beyond popular linear and quadratic models, especially when dealing with large samples. Fractional polynomial models may provide a more adaptive alternative to linear or quadratic models.

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“…[286][287][288] In line with this hypothesis, estrogen replacement therapy (ERT) has been shown to significantly reduce the risk of developing AD. 289 The decrease in testosterone in males occurs as a gradual decline, and therefore, it is believed to have a less detrimental effect on mitochondrial function. 287 The decrease in sex hormone levels, characteristic during aging, affects mitochondrial metabolism by decreasing mitochondrial energy production and calcium efflux while increasing oxidative stress and reactive oxygen species (ROS) release.…”

Section: Role Of Age Environmental Factors and Sex In Admentioning

confidence: 99%

The role of innate immunity in Alzheimer's disease

Ennerfelt

Lukens

2020

Immunological Reviews

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The amyloid hypothesis has dominated Alzheimer's disease (AD) research for almost 30 years. This hypothesis hinges on the predominant clinical role of the amyloid beta (Aβ) peptide in propagating neurofibrillary tangles (NFTs) and eventual cognitive impairment in AD. Recent research in the AD field has identified the brain‐resident macrophages, known as microglia, and their receptors as integral regulators of both the initiation and propagation of inflammation, Aβ accumulation, neuronal loss, and memory decline in AD. Emerging studies have also begun to reveal critical roles for distinct innate immune pathways in AD pathogenesis, which has led to great interest in harnessing the innate immune response as a therapeutic strategy to treat AD. In this review, we will highlight recent advancements in our understanding of innate immunity and inflammation in AD onset and progression. Additionally, there has been mounting evidence suggesting pivotal contributions of environmental factors and lifestyle choices in AD pathogenesis. Therefore, we will also discuss recent findings, suggesting that many of these AD risk factors influence AD progression via modulation of microglia and immune responses.

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The Effect of Estrogen Replacement Therapy on Alzheimer's Disease and Parkinson's Disease in Postmenopausal Women: A Meta-Analysis

Cited by 120 publications

References 49 publications

Women's brain aging: Effects of sex‐hormone exposure, pregnancies, and genetic risk for Alzheimer's disease

Women's brain aging: Effects of sex‐hormone exposure, pregnancies, and genetic risk for Alzheimer's disease

Exogenous Sex Hormone Effects on Brain Microstructure in Women: A diffusion MRI Study in the UK Biobank

The role of innate immunity in Alzheimer's disease

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