“There is something to the idea that men and women, males and females, suffer the effects of infection differently,” said Marlene Zuk, a professor of ecology, evolution and behaviour at the University of Minnesota.

Men tend to have weaker immune systems

There is strong evidence that men are more likely to experience severe infections than women are when they get sick. This was seen in the early days of the Covid pandemic, when men had higher hospitalisation and death rates. The same was true during the 1918 flu pandemic, when many more men than women died.

Some of this could be explained by behaviour, said Dr Matthew Memoli, a principal investigator at the National Institute of Allergy and Infectious Diseases. Research finds in general, men take fewer precautions to avoid getting sick, such as wearing a mask or washing their hands. Men also tend to engage more in unhealthy behaviours, like smoking or drinking alcohol, and they are more reluctant to seek medical care, all of which can lead to worse outcomes when they do fall ill.

But studies in animals and humans show that there are also biological differences when it comes to the male and female immune systems.

“Women often produce or mount greater immune responses” regardless of what the illness is, said Sabra Klein, a professor of molecular microbiology and immunology at Johns Hopkins University.

Differences between the sexes emerge even before an infection takes hold. Females’ immune cells are faster at detecting foreign invaders, like viruses or bacteria. When a threat is identified, the female immune system releases more inflammatory proteins, called cytokines. It also produces more antibodies in response to both viruses and vaccines, which help to fight off an infection.

Of course, there are individual differences, but women “tend to initiate those types of responses much more rapidly, and we get greater activation and greater production” of immune proteins, Klein said.

What explains these differences?

Genetics are thought to play an important role. Several genes involved in the immune system are on the X chromosome, and as you may remember from high school biology, females have two X chromosomes while males have one. As a result, the function of those genes, like detecting viruses or producing cytokines, is slightly heightened in females during an infection, said Montserrat Anguera, an associate professor of biomedical sciences at the University of Pennsylvania School of Veterinary Medicine, who specialises in the topic.

Sex hormones likely factor in, too. Testosterone appears to dampen some aspects of immune functioning, like antibody production, while estrogen enhances it, though estrogen has also been shown to suppress the immune system’s inflammatory response.

There is little research as to why this male-female immunity gap exists, but experts say it likely comes down to evolution and procreation. Zuk hypothesised that these differences arose as a sort of trade-off, in which male biology prioritises procreation over longevity, whereas for females “it’s better to just fend off disease and be around to take care of your offspring”.

So does this mean man flu is real?

Not so fast.

Research from the past few years has found it’s actually women who report the worst symptoms when they have a mild respiratory infection. In one study where scientists deliberately infected healthy young people with an influenza virus, women had a higher number of symptoms and felt crummier than the men.

That’s because a stronger immune system can correspond to more, and more severe, symptoms, Klein said, at least during a mild illness. In fact, many of the things we feel when we’re sick – fever, fatigue, congestion – are caused by the body’s response to the infection.

“You want to have a strong immune system because it helps protect you from disease and helps clear diseases,” said Memoli, who led the flu study. “But your immune system, if it’s too active, can actually hurt you.”

Damage caused by the immune system can also result in symptoms lasting longer. In the most extreme example of this, women are more likely to experience post-infection syndromes, like Long Covid, possibly in part because of an overactive immune system.

No matter who you are, it’s miserable being sick. So if a man – or woman – in your life is complaining about how poorly they feel, fight the urge to roll your eyes. But maybe encourage them to go see a doctor.

Written by: Dana G. Smith

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