title: Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.
abstract: BACKGROUND
  Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain.
  
  
  OBJECTIVE
  To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity.
  
  
  METHODS
  Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo.
  
  
  METHODS
  The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects.
  
  
  RESULTS
  In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years.
  
  
  CONCLUSIONS
  The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Wash 98109-1024, USA. garnet@whi.org
authors.forename: Garnet L
authors.initials: GL
authors.lastname: Anderson
authors.forename: Marian
authors.initials: M
authors.lastname: Limacher
authors.forename: Annlouise R
authors.initials: AR
authors.lastname: Assaf
authors.forename: Tamsen
authors.initials: T
authors.lastname: Bassford
authors.forename: Shirley A A
authors.initials: SA
authors.lastname: Beresford
authors.forename: Henry
authors.initials: H
authors.lastname: Black
authors.forename: Denise
authors.initials: D
authors.lastname: Bonds
authors.forename: Robert
authors.initials: R
authors.lastname: Brunner
authors.forename: Robert
authors.initials: R
authors.lastname: Brzyski
authors.forename: Bette
authors.initials: B
authors.lastname: Caan
authors.forename: Rowan
authors.initials: R
authors.lastname: Chlebowski
authors.forename: David
authors.initials: D
authors.lastname: Curb
authors.forename: Margery
authors.initials: M
authors.lastname: Gass
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hays
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.forename: Susan
authors.initials: S
authors.lastname: Hendrix
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.forename: Judith
authors.initials: J
authors.lastname: Hsia
authors.forename: Allan
authors.initials: A
authors.lastname: Hubbell
authors.forename: Rebecca
authors.initials: R
authors.lastname: Jackson
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.forename: Howard
authors.initials: H
authors.lastname: Judd
authors.forename: Jane Morley
authors.initials: JM
authors.lastname: Kotchen
authors.forename: Lewis
authors.initials: L
authors.lastname: Kuller
authors.forename: Andrea Z
authors.initials: AZ
authors.lastname: LaCroix
authors.forename: Dorothy
authors.initials: D
authors.lastname: Lane
authors.forename: Robert D
authors.initials: RD
authors.lastname: Langer
authors.forename: Norman
authors.initials: N
authors.lastname: Lasser
authors.forename: Cora E
authors.initials: CE
authors.lastname: Lewis
authors.forename: JoAnn
authors.initials: J
authors.lastname: Manson
authors.forename: Karen
authors.initials: K
authors.lastname: Margolis
authors.forename: Judith
authors.initials: J
authors.lastname: Ockene
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: O'Sullivan
authors.forename: Lawrence
authors.initials: L
authors.lastname: Phillips
authors.forename: Ross L
authors.initials: RL
authors.lastname: Prentice
authors.forename: Cheryl
authors.initials: C
authors.lastname: Ritenbaugh
authors.forename: John
authors.initials: J
authors.lastname: Robbins
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Rossouw
authors.forename: Gloria
authors.initials: G
authors.lastname: Sarto
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
authors.forename: Linda
authors.initials: L
authors.lastname: Van Horn
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.forename: Robert
authors.initials: R
authors.lastname: Wallace
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wassertheil-Smoller
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology; D002423:Cause of Death; D015179:Colorectal Neoplasms / Q000453:epidemiology; D003327:Coronary Disease / Q000453:epidemiology; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000627:therapeutic use*; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D005260:Female; D006620:Hip Fractures / Q000453:epidemiology; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D017698:Postmenopause; D016016:Proportional Hazards Models; D011655:Pulmonary Embolism / Q000453:epidemiology; D018570:Risk Assessment; D020521:Stroke / Q000453:epidemiology
chemical_list: D004967:Estrogens; D004966:Estrogens, Conjugated (USP)