Testosterone Tempers Response to Flu Vaccination

Men with high levels of testosterone may have weakened immune systems, which may be the reason why men’s immune systems respond less strongly to vaccinations, according to the results of the first study to show an explicit correlation between testosterone levels, gene expression, and immune responsiveness in humans.

The findings show that the expression of genes regulating lipid metabolism correlate with differing vaccine responses observed between the sexes, and a number of these genes also have been shown to be immunosuppressive and likely regulated by testosterone, according to lead author David Furman, PhD, Research Associate in the Department of Microbiology and Immunology at Stanford University School of Medicine in Stanford, CA. “In addition, elevated levels of free testosterone and expression of such gene signatures appear to be highly detrimental for the production of neutralizing antibodies against influenza in men,” he told ConsultantLive.

In general, males have less robust immune responses for reasons that are not well-understood. The researchers used a systems analysis to investigate this difference by analyzing the neutralizing antibody response to a trivalent inactivated seasonal influenza vaccine and a large number of immune system components, including serum cytokines and chemokines, blood cell subset frequencies, genome-wide gene expression, and cellular responses to diverse in vitro stimuli in 87 patients of various ages.

The men with elevated serum testosterone levels and associated gene signatures exhibited the lowest antibody responses to the flu vaccine.

The researchers also identified a cluster of genes involved in lipid biosynthesis that had been previously shown to be up-regulated by testosterone, which correlated with poor virus-neutralizing activity in men.

The results demonstrate a strong association between androgens and genes involved in lipid metabolism, suggesting that these could be important drivers of the differences in immune responses, Dr Furman said. “We hypothesize that these genes connected with lipid metabolism and immunosuppressive shunt down the response by generating suppressive monocytes and T cells, and could be activated when a critical concentration of testosterone is reached.”

Testosterone’s effect on the immune system may be linked to a man’s evolutionary role, Dr Furman said. “Infection with pathogens constituting evolutionary pressure, such as highly pathogenic influenza virus, SARS infection, or dengue fever, often generates an exacerbated and uncontrolled expansion of immune cells and production of inflammatory cytokines, the so-called cytokine storm, which causes tissue damage, endothelial leakage with pulmonary edema, and lung failure. Therefore, in these cases of evolutionary pressure one can think that mechanisms of immunosuppression (high production of testosterone) might be beneficial, and therefore selected.”

Dr Furman added, “Our study strongly indicates that testosterone supplementation is detrimental. However, it might be positive in cases where the immune response is harmful, for example, in autoimmunity or cytokine storms.”

He noted that “sex steroids have a huge effect in immunity. Primary care physicians should be aware of this when considering vaccination regimes.”

The researchers published their results ahead of print on December 23, 2013 in the Proceedings of the National Academy of Sciences.