ABSTRACT
Estrogen-containing hormone therapy initiated during late postmenopause does not improve
episodic memory (an important early symptom of Alzheimer's disease), and it increases
dementia risk. Cognitive consequences of exogenous estrogen exposures during midlife
are less certain. Observational evidence implies that use of hormone therapy at a
younger age close to the time of menopause may reduce risk of Alzheimer's disease
later in life. However, there are concerns that observational findings may be systematically
biased. Partial insight on this critical issue may be gleaned from results of ongoing
clinical trials involving midlife postmenopausal women (Early versus Late Intervention
Trial with Estrogen; Kronos Early Estrogen Prevention Study). The effects of exogenous
midlife estrogen exposures and Alzheimer risk can also be approached through better
animal models, through carefully designed cohort studies, and through use of surrogate
outcomes in randomized controlled trials in midlife women. Selective estrogen receptor
modulators have the potential to affect cognitive outcomes and also merit additional
study.
KEYWORDS
Alzheimer's disease - estrogen - memory - SERM
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Victor W HendersonM.D.
Stanford University, 259 Campus Drive, HRP Redwood Building
Stanford, CA 94305-5405
Email: vhenderson@stanford.edu
