Objective: The Women's Health Initiative (WHI) study and its ancillary Memory Study (WHIMS) revealed increased rates of cardiovascular risk, cognitive decline and dementia with opposed conjugated equine estrogens (CEE). As a result, previously accepted observational data suggesting cardiovascular and cognitive benefits and reduced risk for dementia with hormone therapy (HT) were largely attributed to 'healthy-user' bias. The present observational, community-based, case-controlled study examined the 'healthy-user' bias theory by comparing cognitive task performance in two groups of postmenopausal women, who were either HT users or non-users.
Design: Participants were 213 non-demented, postmenopausal women residing in the community and in assisted-living facilities who completed a self-report health questionnaire and underwent a 1-h cognitive test battery. To study the independent contribution of variables in the prediction of cognitive performance, we employed a series of hierarchical regression models adding terms in three stages. The first stage included only HT, the second stage added demographics, and the last stage added alcohol, depression and a cardiovascular risk factor (CVRF) composite derived from a confirmatory factor analysis. The CVRF composite consisted of: stroke, diabetes, hypertension, and hypercholesterolemia.
Results: Although independent samples t-tests revealed no statistically significant differences in the CVRF composite and its individual components between the two groups, HT users tended to possess fewer CVRF than non-users. Conversely, HT users were younger and more educated than non-users. HT users outperformed non-users on 7/9 cognitive variables. The full regression model controlling for CVRF, demographic variables, and mood showed HT users outperformed non-users on measures of verbal memory and abstract reasoning.
Conclusions: While there is some evidence HT users possess fewer preexisting CVRF than non-users, the observed positive association between HT and cognition is not completely explained by this trend.