Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal WomenWomen's Health Initiative Memory Study

Abstract

Dementia is an age-associated illness that imposes severe functional impairment on individuals. In 2000, more than 4 million people in the United States had Alzheimer disease (AD), and that number is expected to increase to 13 million by 2050.¹ Milder cognitive impairment affects between one fifth and one third of older adults² and strongly predicts dementia and subsequent institutionalization.³ Case-control studies,^4,5 cross-sectional studies,⁶ and prospective studies^7-9 have reported an association between lower risk of dementia and postmenopausal estrogen supplementation. Meta-analyses of the potential protective effects of estrogen against dementia have reported risk reductions of 29%¹⁰ and 34%.¹¹ However, prospective observational studies have not found a protective effect of estrogen on either cognition or the incidence of dementia.^12,13 In addition, clinical trials of unopposed estrogen in women with AD showed no benefit on cognitive performance,^14-16 and methodological limitations, including the paucity of large, controlled clinical trials, have prevented clear conclusions.^17,18 The mixed findings to date leave unanswered questions about the efficacy of estrogen therapy in preventing cognitive decline and dementia in postmenopausal women.