Cognitive benefits of hormone therapy: cardiovascular factors and healthy-user bias.
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.


METHODS
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.
Wharton
Whitney
W
School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA. wlwharto@medicine.wisc.edu
Dowling
Maritza
M
Khosropour
Christine M
CM
Carlsson
Cynthia
C
Asthana
Sanjay
S
Gleason
Carey E
CE
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015982:Bias; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology*; D016022:Case-Control Studies; D003071:Cognition / Q000187:drug effects*; D003704:Dementia / Q000517:prevention & control*; D004522:Educational Status; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000523:psychology; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006306:Health Surveys; D006801:Humans; D006937:Hypercholesterolemia / Q000209:etiology; D016015:Logistic Models; D017698:Postmenopause; D015995:Prevalence; D012016:Reference Values; D012307:Risk Factors; D011795:Surveys and Questionnaires
D004966:Estrogens, Conjugated (USP)