title: Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial.
abstract: BACKGROUND
  The Women's Health Initiative Estrogen-Alone Trial was stopped early after a mean of 7.1 years of follow-up because of an increased risk of stroke and little likelihood of altering the balance of risk to benefit by the planned trial termination date. Postintervention health outcomes have not been reported.
  
  
  OBJECTIVE
  To examine health outcomes associated with randomization to treatment with conjugated equine estrogens (CEE) among women with prior hysterectomy after a mean of 10.7 years of follow-up through August 2009.
  
  
  METHODS
  The intervention phase was a double-blind, placebo-controlled, randomized clinical trial of 0.625 mg/d of CEE compared with placebo in 10,739 US postmenopausal women aged 50 to 79 years with prior hysterectomy. Follow-up continued after the planned trial completion date among 7645 surviving participants (78%) who provided written consent.
  
  
  METHODS
  The primary outcomes were coronary heart disease (CHD) and invasive breast cancer. A global index of risks and benefits included these primary outcomes plus stroke, pulmonary embolism, colorectal cancer, hip fracture, and death.
  
  
  RESULTS
  The postintervention risk (annualized rate) for CHD among women assigned to CEE was 0.64% compared with 0.67% in the placebo group (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.75-1.25), 0.26% vs 0.34%, respectively, for breast cancer (HR, 0.75; 95% CI, 0.51-1.09), and 1.47% vs 1.48%, respectively, for total mortality (HR, 1.00; 95% CI, 0.84-1.18). The risk of stroke was no longer elevated during the postintervention follow-up period and was 0.36% among women receiving CEE compared with 0.41% in the placebo group (HR, 0.89; 95% CI, 0.64-1.24), the risk of deep vein thrombosis was lower at 0.17% vs 0.27%, respectively (HR, 0.63; 95% CI, 0.41-0.98), and the risk of hip fracture did not differ significantly and was 0.36% vs 0.28%, respectively (HR, 1.27; 95% CI, 0.88-1.82). Over the entire follow-up, lower breast cancer incidence in the CEE group persisted and was 0.27% compared with 0.35% in the placebo group (HR, 0.77; 95% CI, 0.62-0.95). Health outcomes were more favorable for younger compared with older women for CHD (P = .05 for interaction), total myocardial infarction (P = .007 for interaction), colorectal cancer (P = .04 for interaction), total mortality (P = .04 for interaction), and global index of chronic diseases (P = .009 for interaction).
  
  
  CONCLUSIONS
  Among postmenopausal women with prior hysterectomy followed up for 10.7 years, CEE use for a median of 5.9 years was not associated with an increased or decreased risk of CHD, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality. A decreased risk of breast cancer persisted.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00000611.
authors.affiliation: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M3-A410, PO 19024, Seattle, WA 98109. alacroix@whi.org.
authors.forename: Andrea Z
authors.initials: AZ
authors.lastname: LaCroix
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Aragaki
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.forename: Lisa
authors.initials: L
authors.lastname: Martin
authors.forename: Karen L
authors.initials: KL
authors.lastname: Margolis
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
authors.forename: Robert
authors.initials: R
authors.lastname: Brzyski
authors.forename: J David
authors.initials: JD
authors.lastname: Curb
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.forename: Cora E
authors.initials: CE
authors.lastname: Lewis
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology*; D015179:Colorectal Neoplasms / Q000453:epidemiology; D003327:Coronary Disease / Q000453:epidemiology*; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage* / Q000009:adverse effects; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006620:Hip Fractures / Q000453:epidemiology; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D017698:Postmenopause; D012306:Risk; D020521:Stroke / Q000453:epidemiology; D020246:Venous Thrombosis / Q000453:epidemiology
chemical_list: D004967:Estrogens; D004966:Estrogens, Conjugated (USP)