Testosterone could at least partly explain why men have less robust immune responses to vaccines than women, according to a new study.

In a study of 53 women and 34 men of various ages, David Furman, PhD, of Stanford University in Stanford, Calif., and colleagues analyzed the neutralizing antibody response to a trivalent inactivated seasonal influenza vaccine (TIV) as well as immune system components, such as serum cytokines and chemokines. They found elevated antibody responses to TIV and expression of inflammatory cytokines in the serum of women compared with men regardless of age, the researchers reported online ahead of print in the Proceedings of the National Academy of Sciences.

In addition, Dr. Furman’s team identified a cluster of genes involved in lipid biosynthesis that have been found to correlate with poor virus-neutralizing activity in men. This cluster of genes had been shown previously to be up-regulated by testosterone. Men with elevated serum testosterone levels and associated gene signatures exhibited the poorest antibody responses to TIV, according to the investigators.

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“These 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 between males and females,” the authors concluded.

In their report, the researchers “suggest that testosterone acts directly on immune cells by repressing transcription factors … implicated in immune activation; these transcription factors would in turn repress the expression of genes involved in lipid metabolism with immunosuppressive activities, creating a negative feedback loop.”