It has been shown that hormones can influence the response to cardiovascular medications in males and females, but no studies have been carried out on hormone-related response to nutraceuticals. This study investigated the protective effect of sulforaphane (SF) in the presence/absence of 17\u3b2-estradiol (E2) against oxidative stress in primary rat cardiomyocytes. Cells were treated with SF and/or E2 and oxidative stress induced by H2O2. SF and E2 co-treatment led to a higher level of protection against H2O2 and reduced intracellular ROS levels in respect to SF or E2 alone. Co-treatment increased GSH level and the expression of several antioxidant enzymes in respect to SF or E2. The co-treatment induced a higher activation of Akt and ERK1/2 signaling pathways in respect to SF and E2. Transmission electron microscopy analysis revealed that co-treatment was more effective in counteracting H2O2-induced alteration of cell organelles than E2 or SF. Our results demonstrate for the first time that estrogens could enhance SF protective effects, suggesting that nutraceutical efficacy might be different in males and females. This work was supported by Fondazione del Monte di Bologna e Ravenn