Our investigations of the mechanisms that mediate sex differences in RBC predisposition to hemolysis have led to the discovery that testosterone enhances RBC susceptibility to hemolysis via a mechanisms likely to occur during erythropoiesis. Orchiectomy in FVB/NJ mice significantly reduced RBC hemolytic response to osmotic or oxidative stress and enhanced RBC storage and post-transfusion recovery as compared to intact males. TRT in orichiectomy mice restored hemolytic phenotypes. These observations have lead to the hypothesis that exposure to testosterone produces RBCs that are more susceptible to functional decline after blood collection and and storage. Current research projects in Kanias lab are aimed to define the molecular mechanisms by which testosterone modulates erythroid cell biology, and the risks associated with TRT in transfusion medicine.