Relationship between menopausal hormone therapy and breast cancer: A nationwide population‐based cohort study

Objective To explore the risk of breast cancer associated with menopausal hormone therapy (MHT), including the various progestogens used today. Methods The study included postmenopausal women over 40 years from the National Health Insurance Database in South Korea (2011–2014) who either used MHT for over 6 months (MHT group) or never used MHT (non‐MHT group) and were matched 1:1 based on several variables using propensity score matching. Both groups were followed until 2020. Results The non‐MHT and MHT groups comprised 153 736 women each. In Cox proportional hazard analysis with time‐dependent covariates, MHT was associated with an increased risk of breast cancer (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.15–1.3). Tibolone, estradiol valerate (EV)/medroxyprogesterone acetate (MPA), EV/norethisterone acetate (NETA), conjugated equine estrogen (CEE), EV, estradiol hemihydrate (EH), CEE/micronized progesterone (MP), CEE/MPA, EV/MP, EV/MPA, and EH/MP did not increase the risk of breast cancer compared with the non‐MHT group. However, EH/drospirenone (DRSP) (HR 1.51, 95% CI 1.38–1.66), EH/NETA (HR 1.66, 95% CI 1.34–2.06), EH/dydrogesterone (DYD) (HR 1.37, 95% CI 1.12–1.68), and EV/cyproterone acetate (CPA) (HR 1.74, 95% CI 1.54–1.96) increased the risk of breast cancer compared with the non‐MHT group. Conclusions MHT was linked to increased breast cancer risk, but not all MHTs. Specific combined therapies (EH/DRSP, EH/DYD, EH/NETA, and EV/CPA) were associated with higher risk, whereas estrogen alone and tibolone were not. Synopsis Specific progestogens in menopausal hormone therapy were associated with breast cancer risk.