Objective: To review the relation in midlife and beyond between estrogen exposures and episodic memory in women.
Background: Episodic memory performance declines with usual aging, and impairments in episodic memory often portend the development of Alzheimer disease. In the laboratory, estradiol influences hippocampal function and animal learning. However, it is controversial whether estrogens affect memory after a woman's reproductive years.
Method: Focused literature review, including a summary of a systematic search of clinical trials of estrogens in which outcomes included an objective measure of episodic memory.
Results: The natural menopause transition is not associated with the objective changes in episodic memory. Strong clinical trial evidence indicates that initiating estrogen-containing hormone therapy after the age of about 60 years does not benefit episodic memory. Clinical trial findings in middle-aged women before the age of 60 years are limited by smaller sample sizes and shorter treatment durations, but these also do not indicate substantial memory effects. Limited short-term evidence, however, suggests that estrogens may improve verbal memory after surgical menopause. Although hormone therapy initiation in old age increases dementia risk, observational studies raise the question of an early critical window during which midlife estrogen therapy reduces late-life Alzheimer disease. However, almost no data address whether midlife estrogen therapy affects episodic memory in old age.
Conclusions: Episodic memory is not substantially impacted by the natural menopause transition or improved by the use of estrogen-containing hormone therapy after the age of 60 years. Further research is needed to determine whether outcomes differ after surgical menopause or whether episodic memory later in life is modified by midlife estrogenic exposures.
Departments of Health Research and Policy (Epidemiology), and of Neurology and Neurological Sciences, Stanford University, Stanford, CA
Reprints: Victor W. Henderson, MD, MS, Stanford University, 259 Campus Drive, HRP Redwood Building, Stanford, CA 94305-5405 (e-mail firstname.lastname@example.org).
Received for publication November 27, 2008; accepted March 4, 2009
Conflicts of interest: None.
Supported in part by National Institutes of Health R01-AG023038, R01-AG17160.
Off-label use: There is no approved indication for estrogens for the prevention or treatment of memory loss.