Menopausal Hormone Therapy and the Risk of Stroke: A Nationwide Cohort Study

• Published in: Yonsei medical journal Vol. 66; no. 7; pp. 429 - 437
• Main Authors: Choo, Sung Pil, Park, Hyunji, Park, Hyemin, Lee, Inha, Cho, Sihyun, Kim, Changsoo, Lee, Kyung-Yul, Lee, Jae Hoon, Kim, Jong-Youn
• Format: Journal Article
• Language: English
• Published: Korea (South) Yonsei University College of Medicine 01.07.2025; 연세대학교의과대학
• Subjects: Cohort Studies; Estrogen Replacement Therapy - adverse effects; Estrogens - adverse effects; Female; Hormone Replacement Therapy - adverse effects; Humans; Menopause - drug effects; Middle Aged; Norpregnenes - adverse effects; Original; Republic of Korea - epidemiology; Retrospective Studies; Risk Factors; Stroke - chemically induced; Stroke - epidemiology; Stroke - etiology; 의학일반; Republic of Korea; Estrogen replacement therapy; ischemic attack; transient; ischemic stroke
• ISSN: 0513-5796; 1976-2437; 1976-2437
• DOI: 10.3349/ymj.2024.0053

Most studies have reported that the risk of coronary heart disease decreases when menopausal hormone therapy (MHT) is initiated before the age of 60 years or within 10 years of menopause. However, the findings regarding stroke risk remain conflicting. This study investigated the association between the risk of ischemic stroke and MHT, categorized by the type of MHT. This population-based, retrospective cohort study was based on the Korean National Health Insurance Service-National Sample Cohort (2004-2015). Participants were aged 45-60 years with no cardiovascular disease or preexisting stroke, classified as never, past, and current users of MHT. Among the study participants, 16915 (88.77%) women had never undergone MHT, 1437 (7.54%) had previously undergone MHT, and 703 (3.69%) were currently using MHT. During the study period, with a mean follow-up of 11.23±2.13 years, the risk of ischemic events was significantly higher among current users [hazard ratio (HR): 2.98, 95% confidence interval (CI): 1.95-4.57, <0.001], particularly in those using estrogen-only MHT (HR: 3.49, 95% CI: 1.12-10.90, =0.032) and tibolone (HR: 3.52, 95% CI: 2.05-6.03, <0.001), compared to never users. Meanwhile, no significant difference in the risk of ischemic events was observed between past users and never users, even after analyses accounting for estrogen type and progestin co-administration. Women currently receiving MHT without underlying cardiovascular disease exhibited an increased risk of ischemic stroke, particularly those treated with E-only MHT or tibolone. However, this increased risk returned to baseline after discontinuing MHT, indicating that past use of MHT was not associated with an increased risk of ischemic stroke.