Context The literature provides no clear answer as to whether total oestradiol (E2) concentrations increase the risk of incident cardiovascular disease (CVD) in healthy men.

Objective The authors conducted a systematic review and meta-analysis to estimate the predictive value of E2 for CVD, and to identify study features explaining conflicting results.

Data sources Articles were identified by a Medline and Embase search and citation tracking.

Study selection Eligible articles were prospective population-based cohorts and nested case-control studies on E2 and incident cardiovascular disease (CVD), including myocardial infarction, stroke or death from coronary heart disease.

Data-extraction Independent researchers re-expressed associations of E2 and incident CVD in a uniform manner to be used in meta-regression analyses for identification of study features explaining conflicting results, and to estimate the predictive value of E2 for CVD.

Results and conclusions 14 studies out of 128 electronically identified articles were eligible. Data to be used for meta-analysis could be calculated in seven cases, and in the remaining seven cases, data of three more became available by contacting those authors. Overall, a non-significant association was found with an estimated summary RR of 0.98 for a change of >75th versus <25th percentile in E2 (95% CI 0.74 to 1.31). Mean body mass index (BMI) of the study population (βs −0.8, p<0.004), and quality of E2 assay (βs −0.6, p<0.08) may have modified the relationship between E2 and incident CVD. The present systematic review does not provide evidence for a pronounced harmful or beneficial effect of E2 on risk for incident CVD in healthy men. If present, an effect of E2 on risk for CVD might be modulated by BMI.