Objective To clarify the similarities and differences between two models simulating estrogen deficiency by comparing cardiovascular indicators of Ovariectomized (OVX) and Old animals, and to provide evidence to study the myocardial protective mechanism of estrogen receptor G protein-coupled estrogen receptor 30 (GPR30) in selected animal models. Methods OVX and Old animal models were established. Echocardiography, ELISA, Western blot, morphology, and transmission electron microscopy were used to compare the cardiac functions, estrogen level, estrogen receptor protein level in myocardial tissue, myocardial fibrosis, and mitochondrial changes in myocardial tissue. Results The cardiac functions, estrogen level, and estrogen receptor protein level in the OVX group were dependent on time. Cardiac functions in the OVX-8W group were significantly lower than those in the control group, and the estrogen and estrogen receptor protein levels were decreased continuously. Cardiac functions in the Old model group were significantly lower than those in control and OVX groups, and the levels of estrogen and estrogen receptor protein were significantly lower than those in control and OVX-4W groups. In the Old model group, obvious myocardial fibrosis was observed, and myocardial cells were significantly enlarged. The heart-to-body ratio was significantly increased, and the mitochondrial structure in myocardial cells was swollen and deformed. Mitochondrial cristae were broken, and vacuolation was observed. Conclusions Both OVX and Old animal models successfully simulate the decrease in the estrogen level. To study fibrosis related to myocardial infarction and heart failure, and conduct research related to mitochondria and other energy metabolism, it is recommended to choose the Old animal model. If the OVX model is selected, it is recommended that the experimental observation endpoint is more than 4 weeks after OVX. Studies on estrogen, blood pressure, obesity, ischemia and reperfusion should use the OVX model.