Objective  To summarize the available evidence on the cardiovascular effects of cross‐sex steroid use in transsexuals.

Methods  We searched relevant electronic databases and sought additional references from experts. Eligible studies reported on cardiovascular events, venous thromboembolism, blood pressure and fasting serum lipids. Data were extracted in duplicate. We used the random‐effects model to estimate the pooled weighted mean difference (WMD) and 95% confidence intervals (CIs).

Results  We found 16 eligible studies, mostly uncontrolled cohorts of varied follow‐up durations (1471 male‐to‐female (MF) and 651 female‐to‐male (FM) individuals). In the MF individuals, cross‐sex hormone use was associated with a statistically significant increase in fasting serum triglycerides without changes in the other parameters (WMD = 23·39 mg/dl; 95% CI = 4·82–41·95). In the FM individuals, there was a similar increase of triglycerides (WMD = 31·35 mg/dl; 95% CI = 7·53–55·17) and a reduction of high density lipoprotein (HDL)‐cholesterol (WMD = −6·09 mg/dl; 95% CI = −11·44 to −0·73). There was a statistically significant but clinically trivial increase in systolic blood pressure (WMD = 1·74 mmHg; 95% CI = 0·21–3·27). Analyses were associated with significant heterogeneity across studies. There were very few reported cardiovascular events (deaths, strokes, myocardial infarctions or venous thromboembolism), more commonly among MF individuals.

Conclusions  Very low quality evidence, downgraded due to methodological limitations of included studies, imprecision and heterogeneity, suggests that cross‐sex hormone therapies increase serum triglycerides in MF and FM and have a trivial effect on HDL‐cholesterol and systolic blood pressure in FM. Data about patient important outcomes are sparse and inconclusive.