Effect of Oestrogen During Menopause on Risk and Age at Onset of Alzheimer's Disease

Abstract

Background Oestrogen use by postmenopausal women has many health benefits, but findings on the effect of oestrogen in Alzheimer's disease are conflicting. Oestrogen promotes the growth and survival of cholinergic neurons and could decrease cerebral amyloid deposition, both of which may delay the onset or prevent Alzheimer's disease. To investigate whether use of oestrogen during the postmenopausal period affects the risk of Alzheimer's disease, we studied 1124 elderly women who were initially free of Alzheimer's disease, Parkinson's disease, and stroke, and who were taking part in a longitudinal study of ageing and health in a New York City community.Methods Relative risks and age-at-onset distributions were calculated from simple and adjusted Cox proportional hazards models. Standard annual clinical assessments and criterion-based diagnoses were used in follow-up (range 1-5 years).Findings Overall, 156 (12•5%) women reported taking oestrogen after onset of menopause. The age at onset of Alzheimer's disease was significantly later in women who had taken oestrogen than in those who did not and the relative risk of the disease was significantly reduced (9/156 [5•8%] oestrogen users vs 158/968 [16•3%] nonusers; 0•40 [95% CI 0•22-0•85], p<0•01), even after adjustment for differences in education, ethnic origin, and apolipoprotein-E genotype. Women who had used oestrogen for longer than 1 year had a greater reduction in risk; none of 23 women who were taking oestrogen at study enrolment has developed Alzheimer's disease.Interpretation Oestrogen use in postmenopausal women may delay the onset and decrease the risk of Alzheimer's disease. Prospective studies are needed to establish the dose and duration of oestrogen required to provide this benefit and to assess its safety in elderly postmenopausal women.

Amyloid β-protein toxicity and oxidative stress in Alzheimer's disease

“…The loss of these steroids at menopause has been postulated to account for some of the cognitive decline and neurodegeneration that can be seen in AD (Simpkins et al 1994). The results of population-based studies suggesting that the increased incidence of AD in older women may be partially due to estrogen deficit and that the use of estrogen replacement can lower the risk of AD in this group (Henderson et al 1994;Tang et al 1996) are consistent with this hypothesis. In neuronal systems, estrogens have long-term effects via a genomic mode of action on various cellular functions that are important for neuronal survival, including the secretase metabolism of APP (Jaffe et al 1994; for a review, see Honjo et al 1995).…”

Nutzen-Risiko-Analyse einer Hormonsubstitution

“…Studien der jüngsten Zeit lassen es wahrscheinlich erscheinen, daß eine frühzeitig einsetzende Östrogen-Substitution die unter Östrogen-Einfluß stehenden kognitiven Zonen verbessern, das Risiko einer Alzheimer-Erkrankung vermindern sowie den Verlauf derselben mildern [12,24,30]. Tang et al [30] glauben in ihrer Studie demonstrieren zu können, daß das relative Risiko einer Alzheimer'schen Erkrankung in Abhängigkeit von der Dauer der Östrogengabe bis auf ein relatives Risiko von 0,13 absinkt.…”

“…Tang et al [30] glauben in ihrer Studie demonstrieren zu können, daß das relative Risiko einer Alzheimer'schen Erkrankung in Abhängigkeit von der Dauer der Östrogengabe bis auf ein relatives Risiko von 0,13 absinkt.…”

Hormonveränderungen im Alter: genitale und extragenitale Auswirkungen

“…Nach tierexperimentellen Untersuchungen kann das Ö stradiol auch die Alpha-Sekretase anregen, die eine Depositionierung des Amyloids verhindern wü rde [29].…”