Alzheimer's disease: Review of hormone therapy trials and implications for treatment and prevention after menopause

Abstract

Hormonal changes associated with the menopausal transition and postmenopause have the potential to influence processes linked to Alzheimer’s disease symptoms and pathogenesis, but effects of menopause on Alzheimer risk can be addressed only indirectly. Nine randomized clinical trials of estrogen-containing hormone therapy in Alzheimer’s disease patients were identified by a systematic literature search. Findings suggest that hormone therapy does not improve cognitive symptoms of women with Alzheimer’s disease. No clinical trials of hormone therapy address Alzheimer prevention, but one clinical trial provides moderate evidence that continuous, combined estrogen plus progestogen initiated at age 65 years or older increases the risk of dementia. The timing, or critical window, hypothesis suggests that hormone therapy initiated at a younger age in closer temporal proximity to menopause may reduce the risk of Alzheimer’s disease. This hypothesis is supported by observational research but is not addressed by clinical trial data. Unrecognized confounding is of concern in interpreting observational results, and research that helps resolve this issue will have important public health implications. Well-designed cohort studies, convergent evidence from appropriate laboratory models, and long-term clinical trials using surrogate biomarkers of brain function and neural pathology could provide relevant answers. Other estrogenic compounds are of theoretical interest with respect to Alzheimer treatment and risk. Effects of selective estrogen receptor modulators such as raloxifene may differ from those of estrogens; potential effects of phytoestrogens are not well studied.

In Vivo Imaging of Brain Estrogen Receptors in Rats: A 16α-18F-Fluoro-17β-Estradiol PET Study

“…Hormonal treatment with estradiol was found to enhance or facilitate cognition and reduce depression in postmenopausal women and in animal models of reproductive senescence, that is, ovariectomized (OVX) rats (7)(8)(9). Estrogen replacement therapy in postmenopausal women was also found to reduce the symptoms of dementia and may even protect against the development of Alzheimer disease (10). In addition to the beneficial effects of estrogen treatment in postmenopausal women, estrogen therapy has been suggested to improve mood in perimenopausal women (8).…”

Dementia is More Frequent in Women

“…The comparison between sexes has shown a stronger association with the female sex. The prevention da hormonska terapija započeta u mlađoj dobi vremenski bliže menopauzi može reducirati rizik od AB (62).…”

Effects of black cohosh on estrogen biosynthesis in hippocampus of non-human primates ex vivo in vitro and in human neuroblastoma cells in vitro

“…promoting neuronal survival, neuritogenesis and synaptic function, reducing local inflammation of astrocytes and microglia, and facilitating remyelination, respectively [1]. Specifically, estrogens seem to display these characteristics when initiated during the critical window of opportunity close to menopause [2]. Brain, as other tissues, possesses the enzymes necessary for local formation of active hormones, neurosteroids, from inactive precursor hormones.…”