title: Women's Health Initiative estrogen plus progestin clinical trial: a study that does not allow establishing relevant clinical risks.
abstract: OBJECTIVE
  This study aims to determine time differences (differences in restricted mean survival times [RMSTs]) in the onset of invasive breast cancer, coronary heart disease, stroke, pulmonary embolism, colorectal cancer, and hip fracture between the placebo group and the conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg group of the Women's Health Initiative (WHI) trial based on survival curves of the original report and to provide adequate interpretation of the clinical effects of a given intervention.
  
  
  METHODS
  Distribution of survival function was obtained from cumulative hazard plots of the WHI report; Monte Carlo simulation was performed to obtain censored observations for each outcome, in which assumptions of the Cox model were evaluated once corresponding hazard ratios had been estimated. Using estimation methods such as numerical integration, pseudovalues, and flexible parametric modeling, we determined differences in RMSTs for each outcome.
  
  
  RESULTS
  Obtained cumulative hazard plots, hazard ratios, and outcome rates from the simulated model did not show differences in relation to the original WHI report. The differences in RMST between placebo and conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg (in flexible parametric modeling) were 1.17 days (95% CI, -2.25 to 4.59) for invasive breast cancer, 7.50 days (95% CI, 2.90 to 12.11) for coronary heart disease, 2.75 days (95% CI, -0.84 to 6.34) for stroke, 4.23 days (95% CI, 1.82 to 6.64) for pulmonary embolism, -2.73 days (95% CI, -5.32 to -0.13) for colorectal cancer, and -2.77 days (95% CI, -5.44 to -0.1) for hip fracture.
  
  
  CONCLUSIONS
  The differences in RMST for the outcomes of the WHI study are too small to establish clinical risks related to hormone therapy use.
authors.affiliation: 1Peñalolén, Campus Oriente, Department of Obstetrics and Gynecology, School of Medicine, University of Chile, Santiago de Chile, Chile 2Department of Public Health and Epidemiology, University of the Andes, Santiago de Chile, Chile 3Campus Sur, Department of Medicine, School of Medicine, University of Chile, Santiago de Chile, Chile 4Institute of Biomedicine, Research Area for Women's Health, Faculty of Medicine, Catholic University of Santiago de Guayaquil, Guayaquil, Ecuador 5Avansalud, Santiago de Chile, Chile 6School of Medicine, University Finis Terrae, Santiago de Chile, Chile 7Quilín Clinic, Clinical University Hospital Network Chile, School of Medicine, University of Chile, Santiago de Chile, Chile.
authors.forename: Sócrates
authors.initials: S
authors.lastname: Aedo
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cavada
authors.forename: Juan E
authors.initials: JE
authors.lastname: Blümel
authors.forename: Peter
authors.initials: P
authors.lastname: Chedraui
authors.forename: Juan
authors.initials: J
authors.lastname: Fica
authors.forename: Patricio
authors.initials: P
authors.lastname: Barriga
authors.forename: Sergio
authors.initials: S
authors.lastname: Brantes
authors.forename: Cristina
authors.initials: C
authors.lastname: Irribarra
authors.forename: María
authors.initials: M
authors.lastname: Vallejo
authors.forename: Ítalo
authors.initials: Í
authors.lastname: Campodónico
mesh_terms: D001943:Breast Neoplasms / Q000401:mortality; D015179:Colorectal Neoplasms / Q000401:mortality; D003327:Coronary Disease / Q000401:mortality; D015914:Estrogen Replacement Therapy / Q000009:adverse effects* / Q000379:methods; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006620:Hip Fractures / Q000401:mortality; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000009:adverse effects*; D009010:Monte Carlo Method; D010919:Placebos; D016016:Proportional Hazards Models; D011655:Pulmonary Embolism / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000401:mortality; D015996:Survival Rate; D016387:Women's Health
chemical_list: D004966:Estrogens, Conjugated (USP); D010919:Placebos; D017258:Medroxyprogesterone Acetate