title: Hormone therapy dose, formulation, route of delivery, and risk of cardiovascular events in women: findings from the Women's Health Initiative Observational Study.
abstract: OBJECTIVE
  Research comparing hormone therapy (HT) doses, regimens, and routes of delivery in relation to cardiovascular disease (CVD) outcomes has been limited. This study directly compared different estrogen doses, routes of delivery, and HT formulations in postmenopausal women in relation to the risk of coronary heart disease (CHD), stroke, CVD mortality, total CVD, and all-cause mortality.
  
  
  METHODS
  The Women's Health Initiative Observational Study is a multicenter prospective cohort study that was conducted at 40 US sites. Analyses included 93,676 postmenopausal women aged 50 to 79 years at study entry who were recruited from September 1994 to December 1998, with annual follow-up through August 14, 2009.
  
  
  RESULTS
  The mean follow-up was 10.4 years. In direct comparisons, oral estradiol was associated with lower hazard ratios (HRs) for stroke than oral conjugated equine estrogens (CEE; HR, 0.64; 95% CI, 0.40-1.02), but statistical power was limited. Similarly, transdermal estradiol was associated with a moderate but nonsignificantly lower risk of CHD compared with oral CEE (HR, 0.63; 95% CI, 0.37-1.06). For other outcomes, comparisons revealed no appreciable differences by estrogen doses, formulations, or routes of delivery. Absolute risks of CVD events and all-cause mortality were markedly lower in younger women compared with older women.
  
  
  CONCLUSIONS
  In direct comparisons, various HT doses and regimens are associated with similar rates of cardiovascular events and all-cause mortality. However, oral estradiol may be associated with a lower risk of stroke, and transdermal estradiol may be associated with a lower risk of CHD, compared with conventional-dose oral CEE. Additional research is needed to confirm these hypotheses.
authors.affiliation: From the 1Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA; 2Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; 3National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; 4MedStar Health Research Institute, Hyattsville, MD; 5University of Florida College of Medicine-Jacksonville, Jacksonville, FL; 6Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN; 7George Washington University School of Medicine and Health Sciences, Washington, DC; 8Atlanta VA Medical Center, Decatur, GA; 9Division of Endocrinology and Metabolism, Department of Medicine, Emory University School of Medicine, Atlanta, GA; and 10Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Chrisandra L
authors.initials: CL
authors.lastname: Shufelt
authors.forename: C Noel Bairey
authors.initials: CN
authors.lastname: Merz
authors.forename: Ross L
authors.initials: RL
authors.lastname: Prentice
authors.forename: Mary B
authors.initials: MB
authors.lastname: Pettinger
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Rossouw
authors.forename: Vanita R
authors.initials: VR
authors.lastname: Aroda
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Kaunitz
authors.forename: Kamakshi
authors.initials: K
authors.lastname: Lakshminarayan
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Martin
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Phillips
authors.forename: Joann E
authors.initials: JE
authors.lastname: Manson
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000367:Age Factors; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage; D015914:Estrogen Replacement Therapy / Q000379:methods*; D004967:Estrogens / Q000008:administration & dosage*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D009026:Mortality; D017698:Postmenopause; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D016387:Women's Health
chemical_list: D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D004958:Estradiol
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