Twenty-five studies (including one case series with 735 users, one RCT with 168 women, 12 case control studies with over 14,760 women; and 11 cohort studies with at least 1,030,905 person-years of use) were included.
Studies were excluded from summary calculations if they had fewer than five colorectal cancer cases or use of an inappropriate control group.
All but one of the studies was observational. It was not possible to assess the effects of dose, type of oestrogen preparation, and use of combined HRT on colorectal cancer due to insufficient published data.
No difference was found in risks of developing colorectal cancer for ever users of HRT compared to never users (17 studies): RR = 0.89 (95%CI: 0.76, 1.05). No difference was found in risks of developing colon cancer for ever users of HRT compared to never users (15 studies): RR = 0.92 (95%CI: 0.79, 1.08). Significant heterogeneity was found. After omitting the one study accounting for most of the heterogeneity, the remaining studies were homogeneous (P = 0.11) and RR for colon cancer and ever use of HRT = 0.88 (95%CI: 0.80, 0.97). Rectal cancer use was not affected by HRT use (11 studies): RR = 0.97 (95%CI: 0.85, 1.11).
Recency of HRT use and colon cancer: The risk of developing colon cancer was less in recent HRT users than in nonusers (7 studies): RR = 0.67 (95%CI: 0.59, 0.77). No difference was found in risks of developing colon cancer for former users of HRT compared to never users (6 studies): RR = 0.93 (95%CI: 0.82, 1.06).
Duration of use of HRT and colon cancer (4 studies): No difference was found in RR of colon cancer in women who had used HRT for less than 5 years: RR = 1.03 (95%CI: 0.74, 1.44) and those who had used it for five or more years: RR = 0.89 (95%CI% 0.70, 1.14), compared to never users.
Colon cancer subsite: No difference was found in risk of right colon cancer in ever users of HRT with RR = 0.85 (95%CI: 0.65, 1.11) or in left colon cancer with RR = 0.90 (95%CI% 0.75, 1.08), compared to never users.
Fatal colon cancer was less common in ever users of HRT compared to never users (3 cohort studies): RR = 0.72 (95%CI: 0.64, 0.81).