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Semin Reprod Med 2009; 27(3): 275-282
DOI: 10.1055/s-0029-1216280
© Thieme Medical Publishers

Endogenous and Exogenous Estrogen, Cognitive Function, and Dementia in Postmenopausal Women: Evidence from Epidemiologic Studies and Clinical Trials

Elizabeth Barrett-Connor1 , 3 , Gail A. Laughlin2 , 3
  • 1Distinguished Professor, Chief Division of Epidemiology, University of California, San Diego School of Medicine, La Jolla, California
  • 2Assistant Professor, Division of Epidemiology, University of California, San Diego School of Medicine, La Jolla, California
  • 3Department of Family and Preventive Medicine, University of California, San Diego School of Medicine, La Jolla, California
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Publication History

Publication Date:
28 April 2009 (online)

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ABSTRACT

There are more than 200 published scientific papers showing that estrogen has favorable effects on brain tissue and physiology in cell culture and animal models including non-human primates. The biological plausibility for a neuroprotective estrogen effect is overwhelming. However, most studies of endogenous estrogen and cognitive decline or dementia in women fail to show protection, and some suggest harm. Failure to find any consistent association might reflect the limitations of a single time of estrogen assay or poor assay sensitivity. More than half of the observational studies of hormone therapy suggest benefit. Nearly all long-term clinical trials fail to show benefit, and the longer trials tend to show harm. Failure to adequately adjust for self-selection of healthier and wealthier women and publication bias could account for some, or all, of the protective effect attributed to estrogen in observational studies. Overall, the evidence does not convincingly support the prescription of early or late postmenopausal estrogen therapy to preserve cognitive function or prevent dementia.

KEYWORDS

Estrogen - cognitive function - dementia

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Elizabeth Barrett-ConnorM.D. 

Departments of Family and Preventive Medicine and Medicine, University of California

San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0607

Email: ebarrettconnor@ucsd.edu

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