Men with high testosterone and a certain gene cluster may not experience an antibody response after a flu shot, researchers suggested -- a finding that could affect men taking prescription testosterone.
Men with higher levels of serum testosterone had a mean 81% lower antibody response to the flu shot (OR 0.19, 95% CI 0.04-0.80) compared with women, while men with lower levels of testosterone had only a 13% lower response (OR 0.87, 95% CI 0.28-2.69), according to , of Stanford University in Stanford, Calif., and colleagues.
Action Points
- Females had elevated antibody responses to seasonal influenza vaccine and expression of inflammatory cytokines compared with men, a study found.
- The study identified a cluster of genes involved in lipid biosynthesis which was upregulated by testosterone and correlated with poor virus-neutralizing activity in men.
- Men with elevated serum testosterone levels and associated gene signatures had the lowest antibody responses to the vaccine.
Testosterone metabolically interacted with the specific gene cluster, inhibiting antibody responses to infection in adult men, the researchers reported online in the .
When asked about how the use of supplemental testosterone may affect men after a flu shot, Furman told ѻý that results from the group's research strongly indicated a possibility for interference with vaccine effectiveness.
"However, it is important to note that having high levels of testosterone is not sufficient for the observed phenotype -- weak vaccine response. It is rather a combination of the expression of certain genes that we identified and high levels of testosterone that is associated with poor responses to the influenza vaccine," Furman added.
AbbVie, the makers of testosterone supplement AndroGel, declined to comment on the study.
Furman and colleagues said their finding could explain why women have higher rates of sepsis, autoimmune diseases, and overproduction of cytokine levels when they have influenza infections than men do.
Furman told ѻý, "We have started new studies to identify the mechanism underlying our observations, and we are also expanding our research to other human populations." He also noted the potential for testosterone to help mitigate some types of conditions rooted in an overactive immune system.
For the study, the researchers drew blood from 53 women and 34 men, ages 20 to 30 or 60 to 89, after they had been inoculated with the flu shot.
The inflammatory response corresponded with the phosphorylated STAT3 proteins in monocytes, which are known to help regulate inflammation and control the body's response to invasion. But the inflammatory response did not match up with serological responses to the vaccine.
The investigators identified a cluster of genes (module 052) involved with fatty acid metabolism in the blood samples. had shown this gene cluster does .
Women with the identified gene cluster responded to the vaccine, but men with high levels of testosterone and the same gene cluster demonstrated a weak response to the flu shot.
On average, men in the high-testosterone group were 24 years of age and had serum levels of 9.55 pg/mL (range, 4.25-24.78 pg/mL), and the men in the low-testosterone group averaged of 77 years of age and had levels of 2.34 pg/mL (range, 0.58-3.89 pg/mL). The normal range for testosterone is 3.0-10.0 pg/mL.
The interaction between the gene cluster and testosterone levels was significant in the high-testosterone men (P<0.005), but not in the low-testosterone men (P=0.18).
The researchers calculated that the immune response to the vaccine was more likely in men with low testosterone (OR 0.87, 95% CI 0.28-2.69), and less likely in men with high testosterone (OR 0.19, 95% CI 0.04-0.80).
and the for testosterone therapy in adult males state that testosterone therapy should only be used in men with testosterone deficiency.
Disclosures
The Ellison Medical Foundation, the Howard Hughes Medical Institute, and the National Institutes of Health provided grant funding for this research. One co-author was supported by the Vaccine Research Institute.
The authors declared no financial conflicts of interest.
Primary Source
Proceedings of the National Academy of Sciences
Davis M, et al "Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influencza vaccination" Proc Natl Acad Sci USA 2013; DOI: 10.1073/pnas.1321060111.