Background: Sex hormones are believed to play an important role in development and progression of cardiovascular disease. However, the gender gap in onset and mortality is not yet completely understood. Transsexuals undergoing hormone therapy are a promising collective for analysing the effects of sex hormones on cardiometabolic disease. Methods: Aim of this study is to identify gender specific cardiovascular changes attributed to high-dose cross-sex hormone therapy (HT) in male-to-female (MtF) and female to male (FtM) transgender patients by performing an oral glucose tolerance test (OGTT) and 3 Tesla magnet resonance spectroscopy for hepatic (HCL) and myocardial (MYCL) lipid content analysis. The control group (CON) is conducted by age, sex and BMI matched healthy individuals. Results: Until now we included 26 MtF,14 FtM patients and 12 age and BMI matched healthy controls. The mean age was comparable in all 3 groups (MtF 30.12±2.31, FtM 29.72±1,91, CON 30,23±1.22 as well as BMI (22.59±3.81, 21.62±2.53, 21.33±1.20 kg/m2, p=ns, respectively). The mean hormone therapy duration was similar in both groups (MtF 4.58±1.20 vs FtM 2.35±0,95, p=0,29). HOMA Index did not significantly differ between the groups (MtF 1,78±0,92 vs FtM 1,96±1.22 vs CON 1,8±1.01, p=0,3 vs 0,4 vs 0,3 respectively). HCL was significantly higher in MtF than FtM (1,50±0,41 % vs 0.54±0,33 %, p=0,022, respectively). We also found a significant correlation between ejection fraction (EF) and Testosterone levels (Spearmans Rho 0,80, p=0.002). Conclusio: These preliminary data could indicate a positive effect of Testosterone therapy on heart function. Contradictory to current data we found a higher HCL in MtF than FtM suggesting a not so protective estrogen effect when looking at the liver. Long-term studies are warranted to assess whether cross-sex HT results in different outcomes regarding cardiovascular disease.