Cohort Study: Oral Hormone Therapy and Tibolone Increase Cardiovascular Risk in Menopausal Women
28 Nov, 2024 | 18:42h | UTCBackground: Cardiovascular disease is the leading cause of mortality worldwide, with incidence in women increasing notably during the menopausal transition. Menopausal hormone therapy (MHT) effectively alleviates menopausal symptoms but has been associated with cardiovascular risks in previous studies. The impact of contemporary MHT formulations and administration routes on cardiovascular disease risk in women aged 50–58 remains unclear.
Objective: To assess the effect of different types of contemporary MHT on the risk of cardiovascular disease, focusing on various hormone combinations and administration methods.
Methods: This nationwide register-based emulated target trial included 919,614 Swedish women aged 50–58 years between 2007 and 2020 who had not used MHT in the previous two years. Participants were assigned to one of eight treatment groups—including oral and transdermal therapies—or to a non-initiator group. The primary outcomes were hazard ratios (HRs) for venous thromboembolism (VTE), ischemic heart disease (IHD), cerebral infarction, and myocardial infarction, analyzed separately and as a composite cardiovascular disease outcome.
Results: Among the participants, 77,512 were MHT initiators and 842,102 were non-initiators. During follow-up, 24,089 cardiovascular events occurred. In intention-to-treat analyses, tibolone was associated with an increased risk of cardiovascular disease (HR 1.52, 95% CI 1.11 to 2.08) compared with non-initiators. Initiation of tibolone or oral estrogen-progestin therapy was linked to a higher risk of IHD (HRs 1.46 and 1.21, respectively). A higher risk of VTE was observed with oral continuous estrogen-progestin therapy (HR 1.61), sequential therapy (HR 2.00), and estrogen-only therapy (HR 1.57). Per protocol analyses showed that tibolone use was associated with increased risks of cerebral infarction (HR 1.97) and myocardial infarction (HR 1.94).
Conclusions: Use of oral estrogen-progestin therapy was associated with increased risks of IHD and VTE, while tibolone was linked to higher risks of IHD, cerebral infarction, and myocardial infarction but not VTE. These findings underscore the varying cardiovascular risks associated with different MHT types and administration methods.
Implications for Practice: Clinicians should exercise caution when prescribing oral estrogen-progestin therapy or tibolone for menopausal symptom relief, considering the elevated cardiovascular risks. Alternative MHT options, such as transdermal therapies, may offer a safer profile and should be considered.
Study Strengths and Limitations: Strengths include the large, nationwide cohort and the emulated target trial design, which reduces selection bias and confounding. Limitations involve the lack of data on menopausal status, smoking, and body mass index, which may affect cardiovascular risk. Potential misclassification of exposure and adherence could also impact results.
Future Research: Further studies should investigate the cardiovascular effects of specific progestins within MHT formulations and explore the impact of different doses and durations of therapy.