Females and males differ in the energy consumption and nutritional requirements which are based on the interactions between environmental factors and sex hormones. The studies in early 1940s ascertained that females have enhanced capability of producing antibodies. This enhanced immune reactivity in females helps mount an effective resistance to infection and therefore females are less susceptible to viral infections, but can develop immune-pathogenic effects and predisposition to autoimmunity due to hyper immune responses. Sex hormones can also control the immune response via circadian rhythm.
Many hormones like cortisol, known to regulate T cell mediated inflammation, have a circadian rhythm with a maximum peak at 8:00 a.m. and progressively lower levels as the day progresses. Interaction between sex hormones and environmental factors like cigarette smoke and infections lead to variable responses in both genders. There is emerging evidence that sex hormones impact microbial composition and the resulting immune response via secondary metabolites binding with receptors like estrogen receptors (ERs), peroxisome proliferator-activated receptors (PPARs). These differences in immune response can lead to variability in disease phenotypes with autoimmunity occurring more often in females and cancers occurring more in males.