Testosterone Makes Men The Weaker Sex When It Comes To Immunity

You might think of testosterone -- specifically low testosterone -- only in its role in sexual health, but research finds that high testosterone in men could cause problems of its own.

Specifically, testosterone appears to weaken the immune response in men, according to a 2014 study published in the Proceedings of the National Academy of Sciences (PNAS). 

Researchers found that high testosterone levels in men caused a lower immune response to vaccination against influenza, making them more vulnerable to the illness. Women and men with low testosterone both had a more active immune response to vaccination than men with high levels of testosterone.

"This is the first study to correlate poor immune response to testosterone levels in men," says Mark Davis, PhD, the study's senior researcher and a professor of microbiology and immunology at Stanford School of Medicine.

The findings may help explain why men are more susceptible to viral and bacterial infections than women.


High Testosterone and Men's Increased Susceptibility to Infections
The immune system defends the body against foreign invaders like viruses and bacteria. The success of a flu vaccination depends on your immune system's ability to make antibodies against flu virus.

In the PNAS study, the researchers looked at proteins found in the blood of 53 women and 34 men given a flu shot. These proteins, called immune-signaling proteins, told the researchers how strong the response was.

High testosterone levels correlated with lower response.

The researchers also found a gene called Module 52 that was highly activated in men with higher levels of testosterone. "This gene seems to be turned on by testosterone," Dr. Davis says.

"Once it gets turned on, it decreases the immune response. These findings suggest a genetic mechanism for the sex differences observed in the human immune system."

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Immune System Differences in Men and Women

It's already known that sex hormones play a role in immune response. The female hormone estrogen increases immune system inflammation, and the male hormone testosterone decreases it. 

Men are more likely to get infections, and women have a better response to vaccines. 

But these sex differences in health aren't black and white. Women can have an overactive immune system.

When the immune system becomes overactive, it can cause a type of disease called autoimmune disease.

Examples of autoimmune diseases include multiple sclerosis, rheumatoid arthritis, and lupus -- all diseases that are much more common in women.


Evolution and the Immune System
Finding a genetic link between high testosterone and low immune response raises the question of why nature would design the immune system to be influenced by hormone levels.

"Pregnancy may be part of the reason," says Davis. "We know that a woman's immune system needs to be turned up after pregnancy to protect her and her baby."

A woman's immune system gets revved up by estrogen, and this hyper-vigilance may be what causes more frequent autoimmune disease in women.

Evolution may play a role, too, says Natan Bar-Chama, MD, director of male reproductive medicine and surgery at Mount Sinai Medical Center in New York City. 

"There could also be an evolutionary advantage for men to have a weaker immune response," he says. "A weaker immune response may have helped men survive trauma and injury, increasing their chances of survival."

Davis seems to agree. "During evolution, men would be more likely to clash violently with each other," he says.

"A weaker response may be a disadvantage when it comes to infections, but an advantage when it comes to a severe immune response.

We know that women are less likely to survive a severe immune response, called a cytokine storm."

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What This Means for Men's Health
The study also raises the issue of flu vaccine effectiveness. "This was a sophisticated study that sheds light on the role of testosterone in the immune response of humans, but it is still a small study," says Dr. Bar-Chama.

"It does not mean that men should not get flu shots. Less effective does not mean not effective."

The immune system is complicated and relies on a delicate balance to function well. "It may be that men benefit from a somewhat weakened, but not too weakened immune response," Davis says.

"But men who take testosterone to boost their testosterone levels should take note." And, though the idea of boosting the immune system may seem exciting, the ability to actually do it has proved to be elusive.

On the other hand, "we know that low testosterone is linked to increased mortality in men due to bone health and cardiovascular health," Bar-Chama says. 

"So men who have low testosterone along with symptoms of low testosterone can benefit from testosterone restoration therapy." 

How to Boost Immune System Health
"I am not aware of any vitamins or supplements that have been shown to boost the immune system," says Bar-Chama, "Good health is your best booster. That includes reducing stress and getting enough sleep." Other smart lifestyle suggestions:

• Don't smoke.
• Eat lots of fruits, vegetables, and whole grains.
• Maintain a healthy body weight.
• Get plenty of exercise.
• Drink alcohol only in moderation.
• Take steps to avoid infection, like washing your hands frequently and avoiding undercooked meats.
• Keep up with your checkups and screenings.

Testosterone's role in the immune response of men may be to weaken it, but that may not be an all-bad thing.

Men's increased susceptibility to infections may be an evolutionary tradeoff for better survival from massive injuries.

"There are still lots of mysteries when it comes to the immune system," Davis says. "This study opens up some new avenues for exploration."

By Chris Iliades, MD Reviewed by Lindsey Marcellin, MD, MPH From Everyday Health


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