The growing importance of hormonal health is becoming an integral component of modern medicine especially as the focus shifts toward maintaining and boosting immunocompetence in the population. Many plausible benefits of hormonal factors on autoimmunity have received growing attention in recent years from the scientific community. Research has been conducted investigating the relationship between immune system function and sex hormones testosterone and estrogen.
Importantly, the immune systems of men and women are known to function differently with 80% of autoimmune diseases occurring in women who tend to show stronger immune responses than their male counterparts. Stronger immune responses in women produce faster pathogen clearance and improved vaccine responsiveness while also contributing to their increased susceptibility to inflammatory and autoimmune diseases.
Results from previous experimental studies have revealed that testosterone can have a medium-sized immunosuppressive effect on immune function, however, the impact of estrogen can vary depending on the immune marker measured. Such differences in immune function and responses have contributed to health- and life-span disparities between sexes yet the role of hormones in immune system aging remains to be understood.
Immune Differences and Dimorphism
The differences in immunocompetency between male and female patients are associated with varying testosterone and estrogen levels – major regulators of the immune system. Differences in gene expression between the sexes contribute to the concept of immune dimorphism though they are limited to one or a few types of immune cells. Furthermore, genomic differences between sexes have been found to become more prominent after the age of 65 with men having a higher innate and pro-inflammatory activity along with lower adaptive activity.
Female and males have different energy and nutrient requirements largely based on interactions between external factors and sex hormones; interactions between hormones and a patient’s environment, including cigarette smoke and viral infections, can lead to variable responses in both genders. While enhanced immunity has been reported in female patients, making them less susceptible to viral infections, their hyper immune response can predispose them to immune-pathogenic effects. In addition, sex hormones can control the immune response via circadian rhythms and their ability to regulate T-cell mediated inflammation.
Emerging evidence also indicates that sex hormones can impact the gut’s microbial composition and thus, impact immunocompetency. Studies have shown that diet-based effects on the microbiome are more prominent in men than in women implicating that dietary interventions may have an influence on sex-based immune responses.
The gut microbiota landscape can impact the systemic levels of testosterone, changing metabolic profiles which may heighten the risk for chronic disease including diabetes. However, current knowledge of the mechanism by which microbiome-derived sex steroids impact immunity remains limited.
Previous research has shown that hormonal contraceptives can increase bacterial species, highlighting sex-hormone-dependent differences and their effects on systemic immune responses. However, the gut microbial composition can be influenced by a variety of factors outside of hormonal levels, such as genetics and dietary habits.
The mechanism underlying sex hormone expression and immunocompetency continues to be investigated; this may result in the improvement of future designs for targeted therapeutics that mitigate sex hormone-inflammatory activity or autoimmune diseases. Clinicians interested in expanding their knowledge on the role of hormones in immune function and longevity are invited to attend the cutting-edge, interactive online Role of Hormones in Immunocompetency and Longevity workshop taking place on March 13, 2021.