Estrogens, episodic memory, and Alzheimer's disease: a critical update.
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.
Henderson
Victor W
VW
Departments of Health Research & Policy (Epidemiology) and of Neurology & Neurological Sciences, Stanford University, Stanford, California 94305-5405, USA. vhenderson@stanford.edu
D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects*; D004334:Drug Administration Schedule; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004967:Estrogens / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008568:Memory / Q000187:drug effects*; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D048789:Phytoestrogens / Q000009:adverse effects; D017698:Postmenopause; D018570:Risk Assessment; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects; D016896:Treatment Outcome
D004967:Estrogens; D018696:Neuroprotective Agents; D048789:Phytoestrogens; D020845:Selective Estrogen Receptor Modulators