Effects of hormone replacement therapy on cognitive aging and dementia risk in postmenopausal women: a review of ongoing large-scale, long-term clinical trials

The aim of this review is to discuss the purpose, design, and expected findings of several ongoing large-scale, long-term clinical trials studying the effects of hormone replacement therapy (HRT) on cognitive aging and risk of developing dementia. The Women's Health Initiative Study of Cognitive Aging (WHISCA) and the cognitive component of the Women's International Study of long Duration Oestrogen after Menopause--Cognition (WISDOM-COG) (to be completed in 2005 and 2006, respectively) will provide information about the effects of HRT on cognitive aging. The Preventing Postmenopausal Memory Loss and Alzheimer's with Replacement Estrogens study (PREPARE), the Women's Health Initiative Memory Study (WHIMS) and the dementia component of WISDOM-COG (to be completed in 2003, 2005 and 2009, respectively) will address the question of whether estrogens can delay or prevent dementia. These ongoing clinical trials will also be the first to study the effects of estrogen with and without progesterone, and the effects of HRT in women with natural versus surgical menopause, on cognitive aging and risk of dementia. Based on the existing literature, we discuss which specific cognitive areas are most likely to be affected by HRT. We also raise the issue that the type of estrogen agent may affect the outcome of these studies.