Lowering testosterone improves myocardial contractile function, decreases prevalence of left atrial appendage thrombus (LAAT) and pleural effusion, and prolongs survival in male dilated cardiomyopathy (DCM) mice. (A) Plasma testosterone levels (% of non-breeding control mice) in DCM breeders (DCM+S) and non-breeding (DCM-S) littermates. (B) Plasma testosterone levels (% of non-breeding control DCM mice) in the castrated (DCM-S, Cas), castrated supplemented with testosterone (DCM-S, Cas+T) and control DCM-S experimental groups. (C) Prevalence of LAAT; bars represent percent affected mice. (D) Ejection fraction (EF). (E) Pleural effusions (PE) prevalence; bars represent percent affected mice. (F) Lung weight to body weight ratio (LW/BW). (G) Plasma ANP levels. (A–G) Mice analyzed at 20 weeks of age. DCM mice per group is shown; control mice without DCM (dashed line), n = 9–10. Data are mean ± standard error of the mean (SEM). * p < 0.05, *** p < 0.001, **** p < 0.0001, ns = not significant. PE and LAAT were not detected in any control mice without DCM. (H) Kaplan–Meier survival curve for DCM-S (n = 28) vs. DCM-S, Cas mice (n = 13). Survival of control mice without DCM were normal and consistent with wild-type C57BL6/J mice.