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

Abstract

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.

Keywords: breast cancer; cohort studies; hormone replacement therapy; progestin; tibolone.