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

To investigate menopausal hormone therapy's (MHT) overall cancer risks in postmenopausal women.

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.

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).

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.

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.