The Role of Testosterone in Modulating Immune Responses to Vaccination Across Molecular and Systemic Levels

Vaccination remains one of the most effective strategies for preventing infectious disease, yet responses to vaccines vary significantly across individuals. Emerging evidence highlights biological sex—and specifically testosterone—as an important factor influencing immune function and vaccine efficacy. Testosterone, widely recognized as an immunosuppressive hormone, alters cytokine production and immune cell activity, leading to weaker antibody responses in males compared to females. This literature review synthesizes findings from both animal and human studies, including work by Posma, Wunderlich, and Furman, to evaluate testosterone’s role at molecular and systemic levels. Results consistently demonstrate that elevated testosterone levels correlate with reduced vaccine efficacy, impaired protective immunity, and altered inflammatory pathways such as arachidonic acid metabolism. These findings challenge the “one-size-fits-all” model of vaccine administration and raise the possibility of developing sex-specific or personalized vaccine strategies. Understanding the immunomodulatory role of testosterone not only informs future vaccine development but also holds implications for improving public health outcomes through more tailored vaccination approaches.