Vaginal use of estradiol is associated with a reduced risk of rectal cancer in postmenopausal women: A Finnish nationwide case-control study.

OBJECTIVE

We assessed the impact of vaginal estradiol on the risk of rectal cancer.

STUDY

DESIGN

We identified in this nationwide case-control study primary rectal cancer cases with five age-matched control cases in 1994-2019 from our dataset of 1.1 million Finnish postmenopausal women. We excluded users of systemic hormone therapy. Then we traced users of vaginal estradiol (10-25 μg twice a week) from the reimbursement register in 1994-2013, a period in which users could be accurately traced in the database (which was not the case for 2014-2019).

MAIN OUTCOME MEASURES: Odds ratios with 95 % confidence intervals were calculated for rectal cancer risk with adjusted logistic regression models separately for vaginal estradiol users in 1994-2013 (1640 cases, 7889 controls) and for the whole study period of 1994-2019 (2853 cases, 13865 controls).

RESULTS

During follow-up, 494 rectal cancer patients (17 %) and 2826 controls (20 %) used vaginal estradiol (p < 0.001). Users were diagnosed with rectal cancer on average nine years later than non-users (73.9 vs 65.1 years, p < 0.001). Use for ≥3 years was associated with a reduced risk of rectal cancer (OR 0.79, 95 % CI 0.63-0.97) in the 1994-2013 cohort. In the extended 1994-2019 follow-up, risk reductions were similar (0.79, 0.68-0.92), appeared already with <3 years' use (0.85, 0.74-0.97), and persisted for up to 5 years after cessation of vaginal estradiol (0.80, 0.71-0.91).

CONCLUSIONS

Vaginal estradiol use may be associated with a reduced risk of rectal cancer - perhaps due to estradiol infiltration into the rectal mucosa. This possible protecting effect could be an important additional health benefit of vaginal estradiol.