Interventions Associated With Decreased Risk
Use of combination oral contraceptives (COC) for at least 1 year reduces endometrial cancer risk by approximately 40%, as demonstrated by case-control studies and prospective cohort studies.[9,10,11] This decrease in risk persists for at least 15 years after discontinuation of COCs. A meta-analysis of ten case-control studies and one prospective study found an association between risk reduction and duration of use. Overall, 4 years of COC use was associated with a risk reduction of approximately 56%; 8 years, 67%; and 12 years, 72%. The single-prospective study did not show a duration response, but the risk was reduced by 80% after 9 years of follow-up.
A Swedish population-based case-control study confirms these findings. Women who used any type of oral contraceptive had a 30% risk reduction (odds ratio [OR] = 0.7; 95% CI, 0.5–0.9) and women who used progestin-only pills had a 60% risk reduction (OR = 0.4; 95% CI, 0.2–1.4). Women who used COCs for at least 3 years had a 50% risk reduction (OR = 0.5; 95% CI, 0.3–0.7) and those who used COCs for at least 10 years had an 80% risk reduction (OR = 0.2; 95% CI, 0.1–0.4). Overall, risk decreased by 10% per year of COC use and was observed for atypical hyperplasias as well as all grades of invasive tumors.
Several cohort [14,15] and case-control [16,17,18,19,20,21,22,23,24] studies of physical activity and endometrial cancer reveal a weak to moderate inverse relationship, despite varying methods of assessing physical activity levels. For postmenopausal women enrolled in The Netherlands Cohort Study on Diet and Cancer, a 46% reduction (RR = 0.54; 95% CI, 0.34–0.85; P = .002) in risk of endometrial cancer was reported in those women who were physically active 90 minutes or more per day compared with less than 30 minutes each day. One case-control study of 822 endometrial cancer cases and 1,111 population controls showed that regular exercise was associated with a 38% decrease in risk (OR = 0.62; 95% CI, 0.51–0.76) without a trend for increasing duration or intensity of physical activity. The Breast Cancer Detection Project Follow-up Study, using a prospective cohort, did not confirm an association between recent physical activity levels and risk. It is unknown whether physical activity reduces endometrial cancer risk by reducing obesity, by reducing serum estrone levels, or by another mechanism.