To elucidate the molecular mechanism underlying estrogen-mediated cardioprotection in left ventricular (LV) hypertrophy and remodeling, we analyzed myocardial hypertrophy as well as cardiac function and hypertrophy-related protein expression in ovariectomized, aortic banded rats. Wistar rats subjected to bilateral ovariectomy (OVX) were further treated with abdominal aortic stenosis (AC). Effects on LV morphology and function were assessed using echocardiography and expression of protein levels determined by western blot analysis. The heart/body weight ratio was most significantly increased in the OVX-pressure overload (PO) group compared to OVX group and PO group compared to sham. The LV weight/body weight ratio was also significantly increased in the OVX-PO group compared to OVX group and PO group compared to sham. The most significant increases in left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP) and ±dp/dtmax were observed in the OVX-PO group compared to OVX group and represent compensatory phenotypes against hypertrophy. Both eNOS expression and activity was markedly reduced in the OVX-PO group and Akt activity was largely attenuated. Marked breakdown of dystrophin was also seen in hearts of OVX-PO groups. Finally, significant increased mortality was observed in the OVX-PO group following chronic isoproterenol administration. Our results demonstrate that rats subject to ovariectomy are unable to compensate for hypertrophy and showed deteriorated heart function and demonstrated increased mortality. Simultaneous impairment of eNOS and Akt activities and reduced dystrophin by ovariectomy likely contribute to cardiac decompensation during PO-induced hypertrophy in ovariectomized rats.