Menopausal hormone therapy and the risk of type 2 diabetes mellitus: Health Insurance Database in South Korea–based retrospective cohort study

Menopausal hormone therapy (MHT) is known to reduce the incidence of type 2 diabetes mellitus (T2DM); however, since the Women's Health Initiative study, the types and doses of female hormones used for MHT have changed considerably. Therefore, this study was conducted to determine whether MHT, which is currently widely prescribed, increases the risk of T2DM.We performed a retrospective cohort study based on national health insurance data and cancer screening data from 2002 to 2019. We included the MHT group as postmenopausal women older than 40 years who used at least one MHT for at least 6 months between 2003 and 2011. We subclassified the MHT group into five categories; tibolone, combined estrogen plus progestin by the manufacturer (CEPM), oral estrogen, combined estrogen plus progestin by the physician (CEPP), and transdermal estrogen. We selected the non-MHT group as postmenopausal women who had never been prescribed MHT from 2002 to 2019. We compared the incidence of T2DM between the MHT group and the non-MHT group.We enrolled 330,771 women in the MHT group and 798,550 women in the control group. T2DM was diagnosed in 15.2% of the non-MHT group, 16.6% of the tibolone group, 12.1% of the CEPM group, 16.6% of the oral estrogen group, 15.4% of the CEPP group, and 17% of the transdermal estrogen group. In Cox proportional hazard analysis adjusted for variable factors, tibolone, oral estrogen, CEPP, and transdermal estrogen increased the incidence of T2DM. In contrast, there was no change in the risk of T2DM in the CEPM group.MHT, including tibolone, which is currently the most prescribed agent, increased the risk of T2DM; however, CEPM did not increase the risk of T2DM. Only tibolone increased the risk of T2DM in participants older than 70 years.