This nationwide retrospective cohort study used South Korea's National Health Insurance Service database (2007–2020) to evaluate how the type and duration of menopausal hormone therapy (MHT) affect endometrial cancer risk in women aged ≥40 presenting with menopausal symptoms, enrolled 2011–2014 and followed through 2020, after propensity score matching.
Manufacturer-combined estrogen-progestogen (CEPM) was associated with **lower** endometrial cancer risk (HR 0.592, 95% CI 0.437–0.801). Tibolone used for ≤4 years showed no increased risk (HR 0.90, 95% CI 0.61–1.314), but tibolone used >4 years was associated with **significantly higher** risk (HR 1.518, 95% CI 1.152–1.999). MHT use lasting 3–6 years overall was also associated with increased risk (HR 1.499, 95% CI 1.061–2.117). Background incidence was 19 per 100,000 person-years in both MHT and non-MHT groups.
- Physician-combined estrogen-progestogen (CEPP) analysis was underpowered (very wide CI: 0.472–4.607), limiting conclusions for that regimen. - Claims-based data may miss unmeasured confounders (e.g., BMI, smoking, family history) not captured in insurance records. - Findings are from a single-country database and may not generalize to non-Korean populations with different MHT prescribing practices.
For postmenopausal women needing MHT, manufacturer-combined estrogen-progestogen formulations appear to reduce endometrial cancer risk and should be preferred over tibolone for longer-term use. Women using tibolone beyond 4 years warrant closer endometrial surveillance given the observed risk increase.
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