OBJECTIVE: This work assessed associations between colorectal cancer risk and postmenopausal/contraceptive hormones; subgroup analyses included women with a clinically defined family history of cancer. METHODS: A population based case-control study of incident colorectal cancer was conducted among women aged 20-74 years in Ontario and Newfoundland & Labrador, Canada. Incident cases (n = 1,404) were selected from provincial cancer registries and controls (n = 1,203) were identified through property records, and other means, between January 1997 and April 2006. Family history of cancer, exogenous hormone-use, and other risk factors were collected via self-administered questionnaires. Multivariate unconditional logistic regression analyses were used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs). RESULTS: Decreased risks of colorectal cancer were observed with ever-users of: hormonal contraceptives (OR: 0.77; CI: 0.65-0.91), estrogen-only postmenopausal hormones (OR: 0.60; CI: 0.47-0.75), and estrogen-progestin postmenopausal hormones (OR: 0.70; CI: 0.52-0.95). Risk estimates were similar between women with and without a strong familial history of cancer. Age at initiation of hormonal contraceptives was associated with colorectal cancer risk; women who initiated use at younger ages (age <22 years: OR: 0.60; CI: 0.47-0.77) experienced a greater reduced risk of disease than women who initiated use at later ages (age 30+: OR: 0.92; CI: 0.68-1.24; p (trend): 0.0026). CONCLUSIONS: These results indicate that exogenous hormone-use is linked with reduced risk of colorectal cancer among women with a strong familial risk of cancer, consistent with observations on population samples of sporadic colorectal cancer cases. A potential age-effect for use of hormonal contraceptives warrants further attention.