Effect of menopausal hormonal therapy on cardiovascular risks in Korean postmenopausal women: A nationwide cohort study

Objective To evaluate the association between menopausal hormonal therapy (MHT) and the risk of cardiovascular disease (CVD), according to various regimens, dosages, routes of administration and starting ages of MHT. Design A population‐based cohort study using the Korean National Health Insurance Services database. Setting Nationwide health insurance database. Population Women who reported entering menopause at an age of ≥40 years with no history of CVD in the national health examination. Methods The study population comprised 1 120 705 subjects enrolled between 2002 and 2019, categorised according to MHT status (MHT group, n = 319 007; non‐MHT group, n = 801 698). Main outcome measures Incidence of CVD (a composite of myocardial infarction and stroke). Results The incidence of CVD was 59 266 (7.4%) in the non‐MHT group and 17 674 (5.5%) in the MHT group. After adjusting for confounding factors, an increased risk of CVD was observed with the administration of tibolone (hazard ratio, HR 1.143, 95% CI 1.117–1.170), oral estrogen (HR 1.246, 95% CI 1.198–1.295) or transdermal estrogen (HR 1.289, 95% CI 1.066–1.558), compared with the non‐MHT group; the risk was based on an increased risk of stroke. The risk trends were consistent regardless of the age of starting MHT or the physicians’ specialty. Among tibolone users, a longer period from entering menopause to taking tibolone and the use of any dosage (1.25 or 2.5 mg) were linked with a higher risk of CVD, compared with non‐MHT users. Conclusions This nationwide cohort study demonstrated an increased risk of CVD, driven mainly by an increased risk of stroke, among tibolone and oral or transdermal estrogen users, compared with that of non‐MHT users.