title: Effects of postmenopausal hormone therapy on incident atrial fibrillation: the Women's Health Initiative randomized controlled trials.
abstract: BACKGROUND
  Atrial fibrillation (AF) is less prevalent in women versus men, but associated with higher risks of stroke and death in women. The role hormone therapy plays in AF is not well understood.
  
  
  RESULTS
  The Women's Health Initiative randomized postmenopausal women to placebo or conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) if they had a uterus (N=16 608) or to conjugated equine estrogens only if they had prior hysterectomy (N=10 739). Incident AF was identified by ECG and diagnosis codes from Medicare claims or hospitalization records. Hazard ratios for incident AF were estimated using Cox proportional hazards regression. After excluding participants with baseline AF, there were 611 incident AF cases over a mean of 5.6 years among 16 128 estrogen plus progestin participants, and 683 cases over a mean of 7.1 years among 10 251 conjugated equine estrogens alone participants. Incident AF was more frequent in the active groups of both trials, reaching statistical significance in the trial of conjugated equine estrogens alone in women with prior hysterectomy (hazard ratio, 1.17; CI, 1.00-1.36; P=0.045) and in the pooled analysis (hazard ratio, 1.12; CI, 1.00-1.24; P=0.05), but not in the estrogen plus progestin trial (hazard ratio, 1.07; CI, 0.91-1.25; P=0.44). These results were only minimally affected by adjustment for incident stroke, coronary heart disease, and heart failure.
  
  
  CONCLUSIONS
  Incident AF was modestly elevated in hysterectomized women randomized to postmenopausal E-alone, and in the pooled group randomized to E-alone or estrogen plus progestin. The trend in women with intact uterus receiving estrogen plus progestin, considered separately, was not statistically significant.
  
  
  BACKGROUND
  ClinicalTrials.gov; Identifier: NCT00000611.
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA. mvperez@stanford.edu
authors.forename: Marco V
authors.initials: MV
authors.lastname: Perez
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Wang
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Larson
authors.forename: Beth A
authors.initials: BA
authors.lastname: Virnig
authors.forename: Barbara
authors.initials: B
authors.lastname: Cochrane
authors.forename: J David
authors.initials: JD
authors.lastname: Curb
authors.forename: Liviu
authors.initials: L
authors.lastname: Klein
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Martin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Robinson
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wassertheil-Smoller
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000453:epidemiology*; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011372:Progestins / Q000009:adverse effects*; D016016:Proportional Hazards Models; D013997:Time Factors
chemical_list: D004967:Estrogens; D011372:Progestins