Estrogen Plus Progestin and Colorectal Cancer: Long-Term Findings From the Women's Health Initiative Randomized Clinical Trial.

Abstract

<i>Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in</i> JCO <i>or elsewhere, for which the primary end point has already been reported.</i>We report long-term colorectal cancer findings from the Women's Health Initiative trial where 16,608 postmenopausal women with a uterus were randomly assigned to daily conjugated equine estrogen (CEE) 0.625 mg, plus medroxyprogesterone acetate (MPA) 2.5 mg, or placebo. When intervention ended after 5.6 years, although there were 44% fewer colorectal cancers in the intervention group (43 <i>v</i> 72, <i>P</i> = .003), the cancers were more commonly lymph node-positive (59.0% <i>v</i> 29.4%, <i>P</i> = .003). Now after cumulative 24-year follow-up, with 431 colorectal cancers, CEE plus MPA no longer influenced colorectal cancer incidence (215 [0.15, annualized rate %] <i>v</i> 216 [0.15], hazard ratio [HR], 0.95 [95% CI, 0.79 to 1.15]). Although not statistically significant, there were more colorectal cancer deaths with CEE plus MPA (87 [0.049] <i>v</i> 69 [0.041] deaths, HR, 1.20 [95% CI, 0.87 to 1.65], <i>P</i> = .26). Vaginal bleeding (54.1% <i>v</i> 5.2% at 6 months) and breast changes were more frequent in the intervention group. After adjusting for postrandomization vaginal bleeding and breast changes, bowel examinations were significantly delayed in intervention group participants (<i>P</i> = .005), potentially contributing to diagnostic delay. Taken together, the findings suggest no clinically meaningful benefit for about 5 years of CEE plus MPA use on colorectal cancer outcome.