A new study links high testosterone in men to weaker immunological responses following an influenza vaccine, offering a possible explanation for why men suffer greater susceptibility to infections of all kinds.

Investigators from Stanford University say men with higher levels of free testosterone experienced a lower production of antibodies protective against influenza following the vaccination. However, men with lower circulating levels of the sex hormone responded just as strongly as women. Science has long known that men suffer greater rates of bacterial, viral, fungal, and parasitic infections; they also show weaker responses to vaccines not only for influenza but yellow fever, measles, hepatitis, and other diseases.

Conversely, women tend to benefit from higher average levels of signaling proteins passed among immune cells to catalyze inflammation as a primary aspect of the body’s response to infection. Moreover, past research in animals and in the cell-cultures has shown testosterone to hold anti-inflammatory properties, suggesting an antagonistic interplay between the hormone and the immunological system, according to the investigators.

However, the interplay between testosterone and the immune system might prove a bit more complex, given evidence showing no connection between higher levels of the antibodies and a stronger overall immunological response to infection. In addition, testosterone appears to chill inflammatory response by interacting with specific genes, according to Mark Davis, director of Stanford’s Institute for Immunity Transplantation and Infection.

"This is the first study to show an explicit correlation between testosterone levels, gene expression, and immune responsiveness in humans," Davis, said in a statement. "It could be food for thought to all the testosterone-supplement takers out there."

Davis and his colleagues drew from research begun in 2008 at Stanford’s Human Immune Monitoring Core, analyzing blood samples taken from people receiving vaccinations. There, investigators use preeminent technology to examine tens of thousands of variables, including levels of circulating immune-signaling proteins and various subtypes of blood cells. They also assess the immune cell’s 22,000 genes to determine active versus inactive.

Investigator David Furman, a research associate on the team, said the study offers something new. "Most studies don't report on sex differences, a major determinant of variation in immune response," he said.

Among findings, the investigators determined that testosterone affected the immune system by activating a specific set of genes known as “Module 52.” In the chain of circumstances, high levels of free testosterone linked to higher levels of activation of those genes with lowered production of influenza antibodies.

So why would nature design a male sex hormone with an Achilles heel? After all, the same hormone promoting strength and virility — muscles, beard growth, a higher tolerance for risk — leaves men more susceptible to disease.

Davis conjectures the answer might prove sensible under evolutionary strictures. "Ask yourself which sex is more likely to clash violently with, and do grievous bodily harm, to others of their own sex," he said. With traditional responsibility for hunting and security, men tended to experience more violence and, thus, more exposure to infection. Therefore, the immunological system may be right-sized for a higher rate of infections that might otherwise slow a man down.

The Stanford team is working with the French government to learn more about sex differences in the immune system.

Source: Davis M. In Men, High Testosterone Can Mean Weakened Immune Response. PNAS. 2013.