Sex-related differences in cardiovascular diseases are complex and highly context-dependent. The objective of this work was to comprehensively determine key sex differences in the response to acute and chronic adrenergic stimulation in C57Bl/6 mice. In the current work, there was no statistically significant difference in key echocardiographic parameters between male and female C57Bl/6 mice in response to acute adrenergic stimulation (a single sub-cutaneous dose of isoproterenol 10 mg/kg). After chronic adrenergic administration (sub-cutaneous injections of isoproterenol 10 mg/kg/day for 14 days), there was similar degree of cardiac dysfunction, cardiac hypertrophy, and myocardial fibrosis in male and female mice. Similarly, chronic isoproterenol administration induced hypertrophic and fibrotic genes in hearts of male and female mice to the same extent. Intriguingly, gonadectomy of male and female mice did not have a significant impact on isoproterenol-induced cardiac dysfunction as compared to sham-operated animals. In conclusion, the current work demonstrated lack of sex-related differences in isoproterenol-induced cardiac hypertrophy, dysfunction, and fibrosis in C57Bl/6 mice. This study challenges the conventional dogma of the detrimental cardiovascular effects of male sex hormones and the beneficial effects of female sex hormones.