Obscurin is a giant cytoskeletal protein that supports muscle development, tethers intracellular compartments to the sarcolemma, and regulates contraction. In the Obscn-ΔIg58/59 mouse model, expressing obscurin lacking Immunoglobulin (Ig) domains 58 and 59, males exhibit atrial fibrillation accompanied by atrial and ventricular dilation. Following extensive characterization of Obscn-ΔIg58/59 ventricles, we hypothesized that Ig58/59 deletion elicits unique structural, electrical, and functional consequences in the atria. Indeed, electron micrographs of Obscn-ΔIg58/59 atria, but not ventricles, reveal altered ultrastructure with misaligned Z-disks. Spontaneous and stimulated Ca2+ cycling behavior are differentially disrupted in atrial cardiomyocytes from 6- and 12-month Obscn-ΔIg58/59 males. Furthermore, ΔIg58/59 atrial cells show an age-dependent deterioration of the transverse-axial tubule network. These alterations in sarcomeric structure and Ca2+-cycling are associated with changes in the expression and phosphorylation of telethonin (T-cap), theorized to tether t-tubules to the sarcomeric cytoskeleton, and JPH2, which links t-tubules to the sarcoplasmic reticulum. Our work in males indicates that the atria are principally and particularly affected by Ig58/59 elimination and that the Obscn-ΔIg58/59 model mirrors essential aspects of atrial cardiomyopathy. In stark contrast to the males in this line, Obscn-ΔIg58/59 females are phenotypically normal. We sequentially postulated that a) ovarian estrogens and b) dietary phytoestrogens insulate ΔIg58/59 females against cardiac pathologies. To this end, we a) surgically excised the ovaries (OVX) of young Obscn-ΔIg58/59 females or performed sham bilateral surgery, and b) switched them to a soy-free (phytoestrogen-free) chow. Depletion of endogenous and exogenous estrogens induces age-specific remodeling of the left ventricle in ΔIg58/59 females, while either age or stress unmasks arrythmias. Still, the soy-free OVX Obscn-ΔIg58/59 female phenotype is more muted than that of soy-fed Obscn-ΔIg58/59 males. Finally, we examined the effect of soy-diet on male cardiac physiology and found that a soy-free diet ameliorates cardiac dysfunction downstream of ΔIg58/59 deletion in males. Collectively, our work in both sexes emphasizes the profound capacity of phytoestrogens to alter cardiomyopathic phenotypes. Further, it suggests that while ovarian sex hormones (and dietary phytoestrogens) fortify female cardioprotection in this model, additional hormonal and perhaps chromosomal factors shield females facing Ig58/59 ablation.