title: Estrogen plus progestin and colorectal cancer incidence and mortality.
abstract: OBJECTIVE
  During the intervention phase in the Women's Health Initiative (WHI) clinical trial, use of estrogen plus progestin reduced the colorectal cancer diagnosis rate, but the cancers were found at a substantially higher stage. To assess the clinical relevance of the findings, analyses of the influence of combined hormone therapy on colorectal cancer incidence and colorectal cancer mortality were conducted after extended follow-up.
  
  
  METHODS
  The WHI study was a randomized, double-blind, placebo-controlled clinical trial involving 16,608 postmenopausal women with an intact uterus who were randomly assigned to daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or matching placebo (n = 8,102). Colorectal cancer diagnosis rates and colorectal cancer mortality were assessed.
  
  
  RESULTS
  After a mean of 5.6 years (standard deviation [SD], 1.03 years) of intervention and 11.6 years (SD, 3.1 years) of total follow-up, fewer colorectal cancers were diagnosed in the combined hormone therapy group compared with the placebo group (diagnoses/year, 0.12% v 0.16%; hazard ratio [HR], 0.72; 95% CI, 0.56 to 0.94; P = .014). Bowel screening examinations were comparable between groups throughout. Cancers in the combined hormone therapy group more commonly had positive lymph nodes (50.5% v 28.6%; P < .001) and were at higher stage (regional or distant, 68.8% v 51.4%; P = .003). Although not statistically significant, there was a higher number of colorectal cancer deaths in the combined hormone therapy group (37 v 27 deaths; 0.04% v 0.03%; HR, 1.29; 95% CI, 0.78 to 2.11; P = .320).
  
  
  CONCLUSIONS
  The findings, suggestive of diagnostic delay, do not support a clinically meaningful benefit for combined hormone therapy on colorectal cancer.
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Hudson Webber Cancer Research Building, 4221 HWCRC, 4100 John R, Detroit, MI 48201, USA. simonm@karmanos.org
authors.forename: Michael S
authors.initials: MS
authors.lastname: Simon
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.forename: Andrew
authors.initials: A
authors.lastname: Muskovitz
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kato
authors.forename: Alicia
authors.initials: A
authors.lastname: Young
authors.forename: F Allan
authors.initials: FA
authors.lastname: Hubbell
authors.forename: Ross L
authors.initials: RL
authors.lastname: Prentice
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000401:mortality / Q000473:pathology; D057210:Delayed Diagnosis; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy / Q000379:methods; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage*; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D011372:Progestins / Q000008:administration & dosage*; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D018401:Sample Size; D014481:United States / Q000453:epidemiology; D016387:Women's Health
chemical_list: D004966:Estrogens, Conjugated (USP); D011372:Progestins; D017258:Medroxyprogesterone Acetate