Association between type and duration of menopausal hormone therapy and endometrial cancer risk: A population‐based study

OBJECTIVE: To evaluate the association between various types and durations of menopausal hormone therapy (MHT) and the risk of endometrial cancer. METHODS: This nationwide retrospective population-based cohort study used the Korean National Health Insurance Service database from 2007 to 2020. Eligible participants, defined as women aged over 40 years who sought care for menopausal symptoms, were enrolled during 2011-2014 and followed for the development of endometrial cancer until the end of 2020. After propensity score matching, participants were categorized as MHT users or non-users. MHT regimens were classified as tibolone, combined estrogen-progestogen therapy by the manufacturer (CEPM), combined estrogen-progestogen therapy by a physician (CEPP), and others. RESULTS: The incidence of endometrial cancer was 19 per 100 000 person-years (95% confidence interval [CI]: 17-21) in both MHT and non-MHT groups. Use of manufacturer-combined estrogen and progestogen therapy was associated with a significantly lower risk of endometrial cancer (hazard ratio [HR] 0.592, 95% CI: 0.437-0.801), while physician-combined therapy showed no significant association (HR 1.474, 95% CI: 0.472-4.607). Tibolone use was not associated with increased risk when used for four years or less (HR 0.9, 95% CI: 0.61-1.314), but showed a significantly increased risk when used for more than four years (HR 1.518, 95% CI: 1.152-1.999). In duration-based analysis, MHT therapy use between three and six years was also associated with increased risk (HR 1.499, 95% CI: 1.061-2.117). CONCLUSION: Endometrial cancer risk in postmenopausal women is influenced by hormone therapy type and duration. Combined estrogen-progestogen regimens are associated with lower risk, whereas prolonged tibolone use is associated with higher risk, supporting individualized and duration-based monitoring.