Estrogen plus progestin and colorectal cancer in postmenopausal women

N Engl J Med. 2004 Mar 4;350(10):991-1004. doi: 10.1056/NEJMoa032071.


Background: Although the Women's Health Initiative (WHI) trial of estrogen plus progestin in postmenopausal women identified more overall health risks than benefits among women in the hormone group, the use of estrogen plus progestin was associated with a significant decrease in the risk of colorectal cancer. We analyzed features of the colorectal cancers that developed and their relation to the characteristics of the participants.

Methods: In the WHI trial, 16,608 postmenopausal women who were 50 to 79 years of age and had an intact uterus were randomly assigned to a combination of conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The main outcome measures were the incidence, stages, and types of colorectal cancer, as determined by blinded central adjudication.

Results: There were 43 invasive colorectal cancers in the hormone group and 72 in the placebo group (hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.003). The invasive colorectal cancers in the hormone group were similar in histologic features and grade to those in the placebo group but with a greater number of positive lymph nodes (mean +/-SD, 3.2+/-4.1 vs. 0.8+/-1.7; P=0.002) and were more advanced (regional or metastatic disease, 76.2 percent vs. 48.5 percent; P=0.004). In exploratory analyses, women in the hormone group with antecedent vaginal bleeding had colorectal cancers with a greater number of positive nodes than women in the hormone group who did not have vaginal bleeding (3.8+/-4.3 vs. 0.7+/-1.5 nodes, P=0.006).

Conclusions: Relatively short-term use of estrogen plus progestin was associated with a decreased risk of colorectal cancer. However, colorectal cancers in women who took estrogen plus progestin were diagnosed at a more advanced stage than those in women who took placebo.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / prevention & control*
  • Estrogen Replacement Therapy* / adverse effects
  • Estrogens, Conjugated (USP) / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Medroxyprogesterone Acetate / therapeutic use*
  • Middle Aged
  • Neoplasm Staging
  • Postmenopause
  • Uterine Hemorrhage / etiology


  • Estrogens, Conjugated (USP)
  • Medroxyprogesterone Acetate