title: Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women's Health Initiative Randomized Trial.
abstract: BACKGROUND
  While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use.
  
  
  METHODS
  The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided.
  
  
  RESULTS
  After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22).
  
  
  CONCLUSIONS
  In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence.
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM) rowanchlebowski@gmail.com.
authors.forename: R T
authors.initials: RT
authors.lastname: Chlebowski
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
authors.forename: G L
authors.initials: GL
authors.lastname: Anderson
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
authors.forename: G E
authors.initials: GE
authors.lastname: Sarto
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
authors.forename: R
authors.initials: R
authors.lastname: Haque
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
authors.forename: C D
authors.initials: CD
authors.lastname: Runowicz
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
authors.forename: A K
authors.initials: AK
authors.lastname: Aragaki
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
authors.forename: C A
authors.initials: CA
authors.lastname: Thomson
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
authors.forename: B V
authors.initials: BV
authors.lastname: Howard
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
authors.forename: J
authors.initials: J
authors.lastname: Wactawski-Wende
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
authors.forename: T E
authors.initials: TE
authors.lastname: Rohan
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
authors.forename: M S
authors.initials: MS
authors.lastname: Simon
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
authors.forename: S D
authors.initials: SD
authors.lastname: Reed
authors.affiliation: Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (GLA, AKA, CC ); Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA (GES, SDR); Department of Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA (RH); Herbert Wertheim College of Medicine Florida International University, Miami, FL (CDR); Department of Nutritional Sciences and Arizona Cancer Center, University of Arizona, Tucson, AZ (CAT); Star Research Institute / Howard University, Washington, DC (BVH); Department of Social and Preventive Medicine, State University of New York, Memphis, TN (JWW); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (TER); Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI (MSS); Brigham and Women's Health Hospital, Harvard Medical School, Boston, MA (JEM).
authors.forename: J E
authors.initials: JE
authors.lastname: Manson
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000453:epidemiology* / Q000401:mortality / Q000601:surgery; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D015994:Incidence; D053208:Kaplan-Meier Estimate; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000009:adverse effects*; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause; D014481:United States / Q000453:epidemiology; D016387:Women's Health
chemical_list: D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate