Background: Colorectal cancer incidence was reduced among women assigned to active treatment in the Women's Health Initiative (WHI) estrogen plus progestin-randomized trial, but the interpretation was obscured by an associated later stage of diagnosis. In contrast, the estrogen-alone trial showed no incidence reduction or differential stage at diagnosis. Here, data from the WHI observational study are considered, in conjunction with colorectal cancer mortality data from the hormone therapy trials, in an attempt to clarify postmenopausal hormone therapy effects.
Participants and methods: Postmenopausal women ages 50 to 79 years at WHI enrollment. Estrogen-alone analyses include 21,552 and 10,739 women who were posthysterectomy from the observational study and clinical trial, respectively. Estrogen plus progestin analyses include 32,084 and 16,608 observational study and clinical trial women with uterus. Colorectal cancers were verified by central medical and pathology report review.
Results: Hazard ratios (95% confidence intervals) from the WHI observational study were 0.80 (0.53-1.20) for estrogen and 1.15 (0.74-1.79) for estrogen plus progestin, with, respectively, 168 and 175 women diagnosed with colorectal cancer. Delayed diagnosis with estrogen plus progestin is not evident in the observational study. No protective effect on colorectal cancer mortality in the estrogen plus progestin trial is seen over an 8-year intervention and follow-up period.
Conclusion: Hazard ratio patterns in the WHI clinical trial and observational study do not provide strong evidence of a clinically important colorectal cancer benefit with either estrogen-alone or estrogen plus progestin over 7 to 8 years of treatment and follow-up.
Trial registration: ClinicalTrials.gov NCT00000611.