Estrogen + Progestin: No Clinical Benefit for Colorectal Cancer
“No suggestion of reduced colorectal cancer mortality emerged with extended follow-up,” Michael S. Simon, MD, MPH, of the Karmanos Cancer Institute, Wayne State University, Detroit, MI, and colleagues noted.
The WHI trial randomly assigned postmenopausal women with an intact uterus to daily 0.625mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n=8,506) or matching placebo (n=8,102). During the intervention phase of the trial, a 44% lower rate of diagnosis of colorectal cancer was observed in the estrogen plus progestin group.
“Consequently, review articles, position statements, and executive summaries of professional societies commonly listed reduction of colorectal cancer risk as a benefit of estrogen plus progestin use,” Dr. Simon noted.
After a mean of 5.6 years of intervention and 11.6 years of total follow-up, fewer cancers were diagnosed in the combined hormone therapy group, 0.12% per year vs the placebo group, 0.16% per year (HR 0.72; 95% CI, 0.56–0.94; P=0.014). In the estrogen plus progestin arm, the cancers detected more commonly had positive lymph nodes, 50.5%, vs 28.6% in the placebo arm (P<0.001) and were detected at a higher stage (regional or distant, 68.8% vs 51.4%; P=0.003).
The higher number of deaths from colorectal cancer in the combined hormone therapy group (37, vs 27 in the placebo arm) was not statistically significant (HR 1.29; 95% CI, 0.78–2.11; P=0.320).
“These findings, in a cancer that can run a fatal course if there is a delay in diagnosis, do not support a clinically meaningful benefit for use of estrogen plus progestin in colorectal cancer. Future studies of estrogen plus progestin use and colorectal cancer should go beyond incidence analyses to address influence on tumor characteristics, stage, and colorectal cancer mortality,” they concluded.