Twenty studies were included in the review (458,676 participants): four randomised controlled trials (RCTs) (30,278 participants), eight cohort studies (400,934 participants) and eight case-control studies (27,464 participants). Sample sizes ranged from 168 to 94,505; most studies contained several thousand participants. Follow-up time (where reported) ranged from 3.2 to 15 (units not reported).
Ever use of oestrogen therapy was associated with a decreased risk of colorectal cancer (RR 0.74, 95% CI 0.68 to 0.81; 17 studies) as was ever use of combined oestrogen-progestogen therapy (RR 0.79, 95% CI 0.69 to 0.91; 14 studies). There was evidence of significant heterogeneity for the oestrogen only analysis (Ι²=69.2%). When studies were pooled there were no significant differences between oestrogen therapy and combined oestrogen-progestogen therapy for risk of colorectal cancer.
Current use of oestrogen therapy had a significantly lower risk of colorectal cancer (five studies) compared to former use (five studies). There were no significant differences between current (five studies) and former (five studies) use of combined oestrogen-progestogen therapy.
Risk of colorectal cancer was lower than risk of rectal cancer for both oestrogen therapy and combined oestrogen-progestogen therapy, but this difference was not statistically significant.
Other subgroup analyses were reported. Sensitivity analyses did not significantly alter the overall results. There was no evidence of publication bias.