title: Cognitive benefits of hormone therapy: cardiovascular factors and healthy-user bias.
abstract: 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.
authors.affiliation: School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA. wlwharto@medicine.wisc.edu
authors.forename: Whitney
authors.initials: W
authors.lastname: Wharton
authors.forename: Maritza
authors.initials: M
authors.lastname: Dowling
authors.forename: Christine M
authors.initials: CM
authors.lastname: Khosropour
authors.forename: Cynthia
authors.initials: C
authors.lastname: Carlsson
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
authors.forename: Carey E
authors.initials: CE
authors.lastname: Gleason
mesh_terms: 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
chemical_list: D004966:Estrogens, Conjugated (USP)