SummaryExercise could be a therapeutic approach for cardiovascular dysfunction induced by estrogen deficiency. Our previous study has shown that estrogen maintains cystathionine-γ-lyase (CSE) expression and inhibits oxidative stress in the myocardium of female rats. In the present study, we investigated whether exercise improves CSE expression and oxidative stress status and ameliorates isoproterenol (ISO)-induced cardiac damage in ovariectomized (OVX) rats. The results showed that treadmill training restored the ovariectomy-induced reduction of CSE and estrogen receptor (ER)α and decrease of total antioxidant capacity (T-AOC) and increase of malondialdehyde (MDA). The level of CSE was positively correlated to T-AOC and ERα while inversely correlated to MDA. OVX rats showed increases in the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) and the percentage of TUNEL staining in myocardium upon ISO insult compared to sham rats. Exercise training significantly reduced the serum levels of LDH and CK and the percentage of TUNEL staining in myocardium upon ISO insult in OVX rats. In cultured cardiomyocytes, ISO treatment decreased cell viability and increased LDH release, while overexpression of CSE increased cell viability and decreased LDH release in the cells upon ISO insult. The results suggest that exercise training improves the oxidative stress status and ameliorates the cardiac damage induced by oxidative stress in OVX rats. The improvement of oxidative stress status by exercise might be at least partially due to upregulation of CSE/H 2 S signaling. (Int Heart J 2016; 57: 96-103) Key words: Hydrogen sulfide, Estrogens, Estrogen receptor M enopause is a risk factor for many cardiovascular diseases. Cross-sectional data show that the incidence of cardiovascular diseases is much higher in post-menopausal women compared with women of the same age who are pre-menopausal. 1,2) Many studies in animal models have demonstrated that a lack of ovary hormones, in particular estrogens, has detrimental effects on various organs including the cardiovascular system.3) Hormone replacement therapy (HRT) has therefore been recommended to postmenopausal women. However, the controversies regarding the safety of HRT have drawn attention to new therapies for postmenopausal women. 4,5) Exercise training is one of the therapies used to prevent postmenopausal syndrome. Numerous epidemiological studies have convincingly shown that physical exercise has a beneficial effect on cardiovascular disease outcomes. Exercise reduces heart rate and blood pressure, augments myocardial oxygen uptake, and regulates circulating blood volume as well as various metabolic processes.6,7) Furthermore, it has been shown that postmenopausal women who engage in intermittent, moderate-intensity physical training have a decreased risk of cardiovascular complications. 8,9) Oxidative stress is considered one of the main causative factors in various cardiovascular disorders including postmenopausal cardiovascular disorders.10) Ovarian stero...