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Testosterone May Undermine Flu Shot’s Effectiveness for Men

December 23, 2013

By Steven Reinberg
HealthDay Reporter

MONDAY, Dec. 23, 2013 (HealthDay News) — The flu vaccine is less effective for men than women, and researchers at Stanford University believe they’ve figured out why.

The male hormone testosterone causes genes in the immune system to produce fewer antibodies, or defense mechanisms, in response to the vaccine, they found.

“Men, typically, do worse than women in immune response to infection and vaccination,” said Stanford research associate David Furman, the lead study investigator.

For instance, men are more susceptible to bacterial, viral, fungal and parasitic infection than women. And men’s immune systems don’t respond as robustly as women’s to vaccinations against flu, yellow fever, measles, hepatitis and many other diseases, Furman said.

For the study, published online Dec. 23 in the Proceedings of the National Academy of Sciences, the researchers analyzed the blood of nearly 90 adults after they received a seasonal flu shot. Men with the highest testosterone levels had the worst response to the flu vaccine across the board, Furman said.

Testosterone is tied to classic male sexual characteristics, such as muscle strength, beard growth and risk-taking.

“We found a set of genes in men that when activated caused a poor response to the vaccine, but were not involved in female response,” he said. “Some of these genes are regulated by testosterone.”

It’s testosterone’s effect on these genes that causes the poor vaccine response, Furman explained.

“This has a lot of implications for vaccine development,” Furman said. Vaccine response might be better if men were given twice the dose, he suggested, or perhaps if testosterone levels were reduced.

The whole picture isn’t really clear or simple, he noted. Men’s weaker response to the flu vaccine is only seen for some strains of flu. “We don’t know why,” Furman said.

One expert doesn’t think testosterone alone explains the difference in vaccine response between men and women.

“There is more involved, but testosterone does affect the immune response,” said Dr. Alan Mensch, medical director at North Shore-LIJ Plainview Hospital in Plainview, N.Y.

Mensch doesn’t believe it’s necessary to increase vaccine doses for men. Rather, he thinks women can get by with a lower dose.

“There isn’t a difference in the amount of protection from flu. Women just don’t need as much vaccine,” Mensch said.

In this study, which involved 53 women and 34 men, researchers found that, in general, women had a stronger antibody response to the vaccine. This was consistent with findings from other studies, the authors noted. However, men with low testosterone levels had an antibody response similar to women.

Furman’s team also noticed that the activity of certain genes in men, but not women, was associated with a weakened antibody response to the flu vaccine.

When they looked at male testosterone levels in relation to gene activity, they saw increased activation of the Module 52 genes in men with high testosterone levels. This resulted in reduced antibody production for the flu, the researchers concluded.

But in women, activation levels of Module 52 genes had no significant effect on flu antibody levels, the study authors noted.

Some Module 52 genes are known to be related to the immune system. The connections between these genes and testosterone might be a target for further study and drug development, Furman said.

One unanswered question is what evolutionary purpose is served by having testosterone connected to the immune system, Furman said.

It’s possible that an overly robust immune response might be more dangerous than the disease itself. For example, women with their robust immune responses are twice as likely as men to die from infections that invade the blood system, Furman explained.

So maybe a somewhat less robust immune system can be lifesaving for men, he suggested.

More information

For more information on flu vaccine, visit the U.S. Centers for Disease Control and Prevention.


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