Author Affiliations: Evidence-based Practice Center (Drs LeBlanc and Nelson and Mr Chan) and the Departments of Medicine (Dr LeBlanc) and Neurology (Dr Janowsky), and Division of Medical Informatics and Outcomes Research (Dr Nelson and Mr Chan), Oregon Health Sciences University, and Medical Service (Dr Nelson), Veterans Affairs Medical Center, Portland.
Context Some observational data suggest that hormone replacement therapy (HRT)
may reduce the risk of cognitive decline and dementia but results have been
Objective To review and evaluate studies of HRT for preventing cognitive decline
and dementia in healthy postmenopausal women.
Data Sources Studies with English-language abstracts identified in MEDLINE (1966-August
2000), HealthSTAR (1975-August 2000, PsychINFO (1984-August 2000); Cochrane
Library databases; and articles listed in reference lists of key articles.
Study Selection Randomized controlled trials and cohort studies were reviewed for the
effects of HRT on cognitive decline; cohort and case-control studies were
reviewed for dementia risk. No randomized controlled trials regarding dementia
risk were identified.
Data Extraction Twenty-nine studies met inclusion criteria and were rated. Two reviewers
rated study quality independently and 100% agreement was reached on Jadad
scores and 80% agreement was reached on US Preventive Services Task Force
quality scores. A final score was reached through consensus if reviewers disagreed.
Data Synthesis Studies of cognition were not combined quantitatively because of heterogeneous
study design. Women symptomatic from menopause had improvements in verbal
memory, vigilance, reasoning, and motor speed, but no enhancement of other
cognitive functions. Generally, no benefits were observed in asymptomatic
women. A meta-analysis of observational studies suggested that HRT was associated
with a decreased risk of dementia (summary odds ratio, 0.66; 95% confidence
interval, 0.53-0.82). However, possible biases and lack of control for potential
confounders limit interpretation of these studies. Studies did not contain
enough information to assess adequately the effects of progestin use, various
estrogen preparations or doses, or duration of therapy.
Conclusions In women with menopausal symptoms, HRT may have specific cognitive effects,
and future studies should target these effects. The meta-analysis found a
decreased risk of dementia in HRT users but most studies had important methodological
LeBlanc ES, Janowsky J, Chan BKS, Nelson HD. Hormone Replacement Therapy and Cognition: Systematic Review and Meta-analysis. JAMA. 2001;285(11):1489–1499. doi:10.1001/jama.285.11.1489
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