Association between Menopausal Hormone Therapy and Cancer: A Nationwide Retrospective Cohort Study in South Korea

BACKGROUND: To investigate menopausal hormone therapy's (MHT) overall cancer risks in postmenopausal women. METHODS: This retrospective cohort study used South Korea's National Health Insurance System data, focusing on women aged 40 or older diagnosed with initial menopause (2011-2014), comparing an MHT group (≥6 months) with a propensity score-matched non-MHT group for cancer incidence until 2020. RESULTS: We matched 138,445 women per group, followed for a median of 7.9 years. Breast (28%), thyroid (23%), and colorectal (8%) cancers predominated. MHT increased the overall cancer risk [hazard ratio (HR) 1.104; 95% confidence interval (CI), 1.064-1.145], especially estrogen plus progestogen therapy (EPT; HR, 1.172; 95% CI, 1.119-1.227) and estrogen-alone therapy (ET; HR, 1.142; 95% CI, 1.05-1.244), but not tibolone. Breast (HR, 1.568; 95% CI, 1.448-1.697), colorectal (HR, 1.157; 95% CI, 1.018-1.315), brain (HR, 1.618; 95% CI, 1.6-2.258), and renal (HR, 1.378; 95% CI, 1.053-1.803) cancers were more common in MHT; uterine cancer decreased (HR, 0.865; 95% CI, 0.763-0.981). CONCLUSIONS: MHT increased overall cancer risk, with EPT and ET elevating risks, unlike tibolone. MHT users faced higher risks of breast, brain, renal, and colorectal cancers but a lower risk of uterine cancer. IMPACT: These findings suggest considering lower-potency progestogens in current estrogen/progestogen therapy. This change might increase endometrial cancer risk but reduce breast cancer risk, potentially lowering overall cancer risk.