Men have been called out by women for faking it in the bedroom as they lay helplessly after catching a case of the sniffles. The moaning, complaining, and whining that describes the characteristics of the “man flu,” however, may not be a myth after all. According to a recent study published in the journal Life Sciences, estrogen allows women to have stronger immune systems that are more resistant to respiratory illnesses compared to their testosterone-filled counterparts.

Men are thought to have a complete system breakdown when they get a cold as they react differently to women. The tongue-in-cheek expression — man flu — has been coined to describe a man’s way of dealing with the common cold. The self-pitying spectacle of men sinking themselves under the covers sniffling for sympathy and exaggerating they have come down with something more than a cold can well be a partner's source of laughs, but is there any truth to this phenomenon? Do the sexes biologically respond differently to colds?

Professor Lester Kobzik at Harvard University’s School of Public Health and his colleagues sought to investigate whether gender differences do exist when it comes to the resistance of respiratory infections. In the first round, the researchers tested the effect of bacterial pneumonia on mice by introducing the infection to their lungs. The female mice were found to be naturally more resistant to the condition due to the release of the enzyme nitric oxide synthase 3 (NOS3) — activated by the release of estrogen.

In the second round, the researchers took another set of male and female mice and removed the gene responsible for the production of NOS3. The researchers found deleting this gene would no longer make the female mice resistant to infection. A simple dose of estrogen was administered to both males and females in this group. The findings revealed both sexes showed a greater resistance to pneumococcal pneumonia with greater bacterial clearance, diminished lung inflammation and better survival.

This discovery could be used to improve resistance to common and serious lung infections, and possibly prevent the flu from developing into pneumonia. “Ultimately, this work could be especially useful in reducing risk of secondary bacterial pneumonias during seasonal or pandemic influenza. We were quite pleased that the work led us to NOS3-targeting drugs that are already available and that can indeed improve resistance to pneumonia in our mouse model,” Kobzik said, according to a press release.

A similar 2010 study published in the journal Proceedings of the Royal Society, Biological Sciences found evolutionary factors and hormonal differences may make males more susceptible to infection than females. It is believed men suffer from the flu more because they are more likely to engage in risky behaviors that compromise their immune system. The researchers suspect it is possible men evolve less effective immune systems, although this is at odds with “intuitive expectations.”

Sources: Colby A, de Crom R, Huang YC et al. Female resistance to pneumonia identifies lung macrophage nitric oxide Synthase-3 as a therapeutic target. eLife. 2014.

Amos W and Restif O. The evolution of sex-specific immune defences. Proc. R. Soc. B. 2010.