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From the Departments of Neurology (Drs. Henderson and McCleary), Preventive Medicine (Dr. Paganini-Hill), and Obstetrics and Gynecology (Dr. Shoupe), University of Southern California, Los Angeles; the Department of Neurology, University of California at Los Angeles (Dr. Miller) (currently Department of Neurology, University of California at San Francisco); the Department of Neurology (Dr. Elble), Southern Illinois University, Springfield; the Department of Neurology (Dr. Reyes), Jefferson Medical College, Philadelphia, PA; Wyeth-Ayerst Laboratories (Dr. Klein), St. Davids, PA; and the Department of Neurology (Drs. Hake and Farlow), Indiana University, Indianapolis.
Address correspondence and reprint requests to Dr. Victor W. Henderson, Department of Neurology, University of Southern California, 1420 San Pablo Street, PMB-B105, Los Angeles, CA 90089; e-mail: vhenders{at}hsc.usc.edu
BACKGROUND: AD, the most prevalent cause of dementia, affects twice as many women as men. Therapeutic options are limited, but results of prior studies support the hypothesis that estrogen treatment may improve symptoms of women with this disorder.
METHODS: Forty-two women with mild-to-moderate dementia due to AD were enrolled into a randomized, double-blind, placebo-controlled, parallel-group trial of unopposed conjugated equine estrogens (1.25 mg/day) for 16 weeks.
RESULTS: Outcome data were available for 40 women at 4 weeks and 36 women at 16 weeks. At both 4 and 16 weeks, there were no significant differences or statistical trends between treatment groups on the primary outcome measure (the cognitive subscale of the Alzheimer’s Disease Assessment Scale), clinician-rated global impression of change, or caregiver-rated functional status. Exploratory analyses of mood and specific aspects of cognitive performance also failed to demonstrate substantial group differences.
CONCLUSIONS: Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD. These findings do not address possible long-term effects of estrogen in AD, possible interactions between estrogen and other treatment modalities, or putative effects of estrogen in preventing or delaying onset of this disorder.
Key words: AD—Clinical trial—Cognition—Estrogen—Mood—Women
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K. Rockwood, S. Kirkland, D. B. Hogan, C. MacKnight, H. Merry, R. Verreault, C. Wolfson, and I. McDowell Use of Lipid-Lowering Agents, Indication Bias, and the Risk of Dementia in Community-Dwelling Elderly People Arch Neurol, February 1, 2002; 59(2): 223 - 227. [Abstract] [Full Text] [PDF]
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S. Asthana, L. D. Baker, S. Craft, F. Z. Stanczyk, R. C. Veith, M. A. Raskind, and S. R. Plymate High-dose estradiol improves cognition for women with AD: Results of a randomized study Neurology, August 28, 2001; 57(4): 605 - 612. [Abstract] [Full Text] [PDF]
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D. Cosgrove, C. D. Toran-Allerand, and R. A. Mulnard Estrogen as a Treatment for Alzheimer Disease JAMA, July 19, 2000; 284(3): 307 - 308. [Full Text] [PDF]
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S. S. Petanceska, V. Nagy, D. Frail, and S. Gandy Ovariectomy and 17{beta}-estradiol modulate the levels of Alzheimer's amyloid {beta} peptides in brain Neurology, June 27, 2000; 54(12): 2212 - 2217. [Abstract] [Full Text] [PDF]
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L. Wang, S. Andersson, M. Warner, and J.-A. Gustafsson Morphological abnormalities in the brains of estrogen receptor beta knockout mice PNAS, February 27, 2001; 98(5): 2792 - 2796. [Abstract] [Full Text] [PDF]
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