Men with high testosterone levels had less protection from the flu vaccine than women and men who had lower levels of the male sex hormone. But overall, vaccinated women created more antibodies that fight the flu than men did.
"This is the first study to show an explicit correlation between testosterone levels, gene expression and immune responsiveness in humans," Mark Davis, professor of microbiology and immunology and director of Stanford's Institute for Immunity, Transplantation and Infection in Palo Alto, Calif., said in a press release. "It could be food for thought to all the testosterone-supplement takers out there."
Women have more signaling proteins that immune cells use as a sign to turn on inflammation, which jump starts the immune system. Testosterone has also been shown in cell and animal experiments to have anti-inflammatory properties.
Past research has found that men are more likely to suffer from bacterial, viral, fungal and parasitic infections than women. Men's immune systems also don't mount as strong a a response when given flu, yellow fever, measles and hepatitis vaccines, previous studies have shown.
Researchers for the new study, which was published on Dec. 23 in the Proceedings of the National Academy of Sciences, looked at samples from 53 women and 34 men who were given the flu vaccine.
Women created more disease-fighting antibodies than men. However, the researchers didn't see any link between having more pro-inflammatory proteins and a heightened response to the flu vaccine, which suggests something else -- the testosterone levels -- were the driving factor.
But, testosterone was also not shown to lower the immune system response directly. Instead, it seemed to work with specific genes called Module 52 to decrease the response. The more those genes were activated in men, the fewer antibodies were created. For women, the activity of Module 52 didn't seem to matter as much when it came to producing antibodies.
The researchers looked closer at the 34 men and divided them into groups of high-testosterone producers and low-testosterone producers. The high-testosterone group had higher activation levels of Module 52 -- which went hand-in-hand with fewer antibodies -- than those in the low group.
Researchers hypothesize that males evolved this way in order to protect themselves from their own immune systems. Men are more likely to get injured in fights and competitions and in ancient times, they were prone to be injured during traditional tasks like hunting, defending their family or building shelters.
All these activities may increase infection risk. However, having your body over respond to a virus or bacteria can cause an even more dangerous, potentially fatal disease called sepsis, which is when the whole body creates an inflammatory response. It is known that women are twice as likely to die from sepsis as men.
Davis added that since men are more likely to contract viruses and bacteria, the study suggests their bodies try to protect them against sepsis, since they use their immune system more often.
"Ask yourself which sex is more likely to clash violently with, and do grievous bodily harm to, others of their own sex," Davis said.