Menopausal hormone therapy and cognition

Maki, Pauline M.; Girard, Lucille M; Manson, JoAnn E.

doi:10.1136/bmj.l877

Cited by 28 publications

(19 citation statements)

References 11 publications

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“…In this regard, several research studies on interventions aimed at hormone replacement have been conducted. In some cases, hormone supplementation (or HRT, Hormone Replacement Therapy) with estradiol has generated enormous interest for its potentially beneficial effects ( 36 , 37 ). Specifically, menopause-related obesity and loss of lean and skeletal muscle mass have been shown to reverse following estradiol hormone therapy ( 38 ).…”

Section: Future Perspectivesmentioning

confidence: 99%

Sarcopenia and Menopause: The Role of Estradiol

et al. 2021

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During aging and menopausal transition in women, a progressive muscle degeneration (i.e. decrease in quality and muscle function) occurs. This muscle dysfunction, caused by decreased proliferation of muscle satellite cells, increased levels of inflammatory markers, and altered levels of sex hormones, exposes women to a raised incidence of sarcopenia. In this regard, hormonal balance and, in particular, estradiol, seems to be essential in skeletal muscle function. The role of the estradiol on satellite cells and the release of inflammatory cytokines in menopausal women are reviewed. In particular, estradiol has a beneficial effect on the skeletal muscle by stimulating satellite cell proliferation. Skeletal muscle can respond to estrogenic hormonal control due to the presence of specific receptors for estradiol at the level of muscle fibers. Additionally, estradiol can limit inflammatory stress damage on skeletal muscle. In this review, we primarily focused on the role of estradiol in sarcopenia and on the possibility of using Estradiol Replacement Therapy, which combined with nutritional and physical activity programs, can counteract this condition representing a valid tool to treat sarcopenia in women.

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Section: Future Perspectivesmentioning

confidence: 99%

Sarcopenia and Menopause: The Role of Estradiol

et al. 2021

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“…Nevertheless, a recent review has suggested that OVX results in a “blank ovarian hormone state,” which is an ideal model to evaluate the effects of ovarian hormone deprivation and the outcomes of subsequent exogenous hormone treatments on the brain (Koebele and Bimonte-Nelson, 2016 ). Indeed, epidemiological data regarding women who underwent OVX before the onset of natural menopause indicate a long-term increased risk of AD (Rocca et al, 2010 ) and furthermore ERT efficacy is similar in both natural menopause and oophorectomy in women, depending on the timing of treatment initiation (Mosconi et al, 2004 ; Maki et al, 2019 ). Given that female mice continue to experience hormonal cycles with age (Hung et al, 2003 ), the use of OVX can be considered an effective model to mimic human/primate menopause in mice.…”

Section: Discussionmentioning

confidence: 99%

Estradiol Replacement at the Critical Period Protects Hippocampal Neural Stem Cells to Improve Cognition in APP/PS1 Mice

Qin

et al. 2020

Front. Aging Neurosci.

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It has been suggested that there is a critical window for estrogen replacement therapy (ERT) in postmenopausal women with Alzheimer's disease (AD); however, supporting evidence is lacking. To address this issue, we investigated the effective period for estradiol (E2) treatment using a mouse model of AD. Four-monthold female APPswe/PSEN1dE9 (APP/PS1) mice were ovariectomized (OVX) and treated with E2 for 2 months starting at the age of 4 months (early period), 6 months (mid-period), or 8 months (late period). We then evaluated hippocampal neurogenesis, β-amyloid (Aβ) accumulation, telomerase activity, and hippocampaldependent behavior. Compared to age-matched wild type mice, APP/PS1 mice with intact ovaries showed increased proliferation of hippocampal neural stem cells (NSCs) at 8 months of age and decreased proliferation of NSCs at 10 months of age; meanwhile, Aβ accumulation progressively increased with age, paralleling the reduced survival of immature neurons. OVX-induced depletion of E2 in APP/PS1 mice resulted in elevated Aβ levels accompanied by elevated p75 neurotrophin receptor (p75 NTR) expression and increased NSC proliferation at 6 months of age, which subsequently declined; accelerated reduction of immature neurons starting from 6 months of age, and reduced telomerase activity and worsened memory performance at 10 months of age. Treatment with E2 in the early period post-OVX, rather than in the mid or late period, abrogated these effects, and p75 NTR inhibition reduced the overproliferation of NSCs in 6-month-old OVX-APP/PS1 mice. Thus, E2 deficiency in young APP/PS1 mice exacerbates cognitive deficits and depletes the hippocampal NSC pool in later life; this can be alleviated by E2 treatment in the early period following OVX, which prevents Aβ/p75 NTR-induced NSC overproliferation and preserves telomerase activity.

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“…The timing of HRT use may be crucial, such that there is a critical window which exogenous hormone use can confer cognitive bene ts in postmenopausal women. 29,40 Strengths and limitations…”

Section: Exogenous Hormone Usementioning

confidence: 99%

Reproductive Factors and the Risk of Incident Dementia: Results From the UK Biobank

Gong¹,

Peters²,

Woodward³

2021

Preprint

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Background: To examine the risk of incident all-cause dementia associated with reproductive factors in women, and the number of children in both sexes; and whether the effects vary by age, socioeconomic status (SES), smoking status and body mass index in the UK Biobank.Methods: A total of 273,265 women and 228,966 men without prevalent dementia from the UK Biobank were included in the analyses. Cox proportional hazard regressions estimated hazard ratios (HRs) for reproductive factors with incident all-cause dementia.Results: Over a median of 11.3 years follow-up, 1,680 dementia were recorded in women and 2,021 in men. Adjusted HRs (95% confidence intervals (CIs)) for dementia were 1.20 (1.08, 1.35) for menarche <12 years, and 1.24 (1.10, 1.39) for menarche ≥15 years compared to 13 years; 0.86 (0.74, 1.00) for ever been pregnant; 0.80 (0.69, 0.93) for each abortion; 1.29 (1.12, 1.49) for menopause at <47 compared to 50 years; 1.13 (1.01, 1.27) for hysterectomy; 0.80 (0.72, 0.90) for oral contraceptive pills use; and 1.56 (1.40, 1.73) for hormone replacement therapy (HRT) use. The U-shaped associations between the number of children and the risk of dementia were similar for both sexes. There was evidence for early (natural and artificial) menopause, and a greater number of children were associated with a higher risk of dementia among women of relatively lower SES only.Conclusions: Shorter cumulative endogenous estrogen exposure in women is associated with higher dementia risk, although female biological factors involved in childbearing are unlikely to account for risk variation.

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Menopausal hormone therapy and cognition

Abstract: Evidence is reassuring for women needing a few years’ treatment for menopausal symptoms

Cited by 28 publications

References 11 publications

Sarcopenia and Menopause: The Role of Estradiol

Sarcopenia and Menopause: The Role of Estradiol

Estradiol Replacement at the Critical Period Protects Hippocampal Neural Stem Cells to Improve Cognition in APP/PS1 Mice

Reproductive Factors and the Risk of Incident Dementia: Results From the UK Biobank

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