Measurements of Postmenopausal Serum Estradiol Levels and Cardiovascular Events: A Systematic Review.

Background: Cardiovascular disease (CVD) is the leading cause of death among female patients and its likelihood increases following menopause. However, whether estradiol levels are related to CVD remains unknown. We aimed to determine the association between serum estradiol levels and cardiovascular (CV) events in postmenopausal females. Methods: Electronic databases (MEDLINE, Embase) were searched systematically from inception to October 2022. Studies were eligible for inclusion if they included the following: (i) postmenopausal females; (ii) examination of the association between total serum estradiol levels and CV events (CV mortality, CVD, coronary heart disease, myocardial infarction, stroke, venous thromboembolism, heart failure, and CV hospitalization); (iii) original data (randomized controlled trial, quasi-experimental, cohort, case-control, or cross-sectional study). A narrative synthesis was completed because the data were not amenable to meta-analysis. Results: Of the 9026 citations retrieved, 8 articles were included, representing a total of 5635 women. The risk-of-bias was fair, and considerable heterogeneity was present. In those not using menopausal hormone therapy, 3 studies demonstrated mixed results between estradiol levels and risk of coronary heart disease, and 1 study showed that higher estradiol levels were associated with an increased risk of myocardial infarction. No significant associations were present between estradiol levels and the remaining events (ie, CV mortality, heart failure, CVD, and stroke). Conclusions: The association between serum estradiol levels and CV events in postmenopausal females remains unclear. Further studies assessing this association are warranted, given the elevated CVD risk in this population.