Study links menopausal hormone therapy to various risks for heart and blood clots

Research shows that oral estrogen-progestin therapy increases the risk of heart disease and blood clots, while tibolone increases the risk of stroke and heart attack but not blood clots

In a recent study published in BMJ, Researchers evaluated the results of 138 nested trials (between 2007 and 2018) investigating the effects of conventional menopausal hormone therapy on cardiovascular disease (CVD) risk.

The cohort of more than 919,000 women across eight combinations of hormone types and routes of administration revealed that up to 43.0% of hormone users experienced adverse cardiovascular events, with ischemic heart disease (43%) and venous thromboembolic events being the most common .

Tibolone and oral estrogen-progestin therapy were found to be associated with the highest risk of ischemic heart disease. Tibolone significantly increased the risk of stroke and myocardial infarction.

These findings highlight the relative risks of several conventional hormone therapies during menopause, providing physicians and users with the knowledge needed to make safer choices.

About the study

The present study addresses existing knowledge gaps by utilizing a large (N = 919,614) nationwide Swedish cohort (age = 50–58 years) to investigate the relative CVD risk correlates of the current spectrum of systemic menopausal hormone therapy.

Since different methods of hormone delivery target different physiological pathways, this targeted trial research may provide clues to mechanistically support hormone-CVD risk associations, allowing clinicians to recommend the safest choice among the wide range of available interventions.

Study data were obtained from Statistics Sweden, a comprehensive public health registry of Swedish citizens, which includes demographic, socioeconomic, anthropometric, and medical history datasets. Mortality information and hormone prescriptions were obtained from the Swedish National Board of Health and Welfare and the Anatomical Therapeutic Chemical Codes repository.

The present study included 138 nested tests performed monthly between July 2007 and December 2018, each with a two-year follow-up period. Age-appropriate participants with no prior history of prolonged hormone use were included in the data set. Conversely, those who reported significant prior adverse cardiovascular events were excluded for improved accuracy of results.

International Classification of Diseases (ICD-10) codes were used to assign CVD events to participants during the study period, with an emphasis on myocardial infarction (I21, I22), cerebral infarction (I63), and venous thromboembolism (I26, I80, I81, I82).

Cox proportional hazard modeling was used to calculate the relative risks of different hormones and routes of administration, both for individual diseases and for CVD overall.

Study findings

The study revealed that 24,089 of the 919,614 participants suffered a CVD event during the study period. Ischemic heart disease (43.0%; n = 10,360) and toxic thromboembolic events (38.2%; n = 9,196) were the most prevalent, followed by myocardial infarction (17.9%; n = 4,312) and cerebral infarctions (4%, 97 = 1). ).

Surprisingly, in the holistic assessment of CVD risk, no statistically significant differences could be found between initiators (participants receiving hormone therapy) and non-initiators. However, when considering specific routes of administration or hormonal options, tibolone and oral estrogen-progestin therapy were found to be associated with a significantly higher risk of ischemic heart disease (HR = 1.46 and 1.21, respectively).

Results by different routes of administration varied similarly, with continuous oral estrogen-progestin therapy and sequential therapy significantly increasing the risk of VTE (HR = 1.61 and 2.00, respectively), compared with no with estrogen alone (HR = 1.57).

Together, these findings help explain the confounding results from previous single-hormone comparisons and highlight how some hormones and routes of administration are safer choices related to CVD compared to others.

conclusions

The present study highlights differences in CVD risk outcomes following various conventional approaches to menopausal hormone therapy, which are further exacerbated by specific hormone choices.

Oral estrogen-progestin therapy was found to significantly increase the risk of venous thromboembolism, while the hormone tibolone contributed significantly to ischemic heart disease and myocardial and cerebral infarction outcomes.

Together, these findings help explain previous discrepancies in research findings and highlight the need for holistic, multivariate assessments in studies involving complex physiological interactions. Proceeds from these findings will help clinicians and public health agencies recommend the safest therapeutic interventions from the available spectrum, thereby potentially reducing the burden of the prevalence of female menopausal-related cardiovascular disease.