Furman · Proceedings of the National Academy of Sciences of the United States of America 2014 · prospective cohort study · n=87

Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination.

Cited 701 times in the scientific literature.

Level 3 - non-randomized controlled study

Non-randomized observational cohort study evaluating multi-omics immune responses by sex.

PubMed 24367114 · doi:10.1073/pnas.1321060111 · record verified 2026-08-26

What was done

Researchers evaluated neutralizing antibody responses, serum cytokines and chemokines, blood cell subset frequencies, genome-wide gene expression, and in vitro cellular responses following trivalent inactivated seasonal influenza vaccination (TIV) in 53 females and 34 males of different ages using a systems biology and machine learning approach.

What was found

Females demonstrated elevated antibody responses to TIV and increased serum inflammatory cytokines compared with males across all ages. Inflammatory profiles correlated with monocyte phosphorylated STAT3 levels, but not serological response. In males, a machine-learning-identified gene cluster involved in lipid biosynthesis correlated with poor virus-neutralizing activity, and men with elevated serum testosterone and associated gene signatures showed the lowest antibody responses. The abstract reports no numerical values, effect sizes, or p-values.

Why it matters

This work identifies a potential endocrine-mediated molecular pathway linking testosterone and lipid metabolism to reduced humoral vaccine responses in men.

Limits

The total sample size was modest (n = 87, with only 34 males), no specific numerical values or confidence intervals were reported in the abstract, and the observational design establishes correlation rather than direct causal immunosuppression by testosterone.

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