I was browsing the website of the BMJ Christmas editions, and my attention was caught by an article about ‘The science behind man flu’ written by Kyle Sue . Recently, this article was in the Dutch papers NRC and Volkskrant and called unscientific [2, 3]. However, I was curious about the concept of the “man flu” and did some research.
I think every woman in a relationship with a man can relate to the concept of the “man flu”. The Oxford dictionary defines it as: “A cold or similar minor ailment as experienced by a man who is regarded as exaggerating the severity of the symptoms.” I also think that every man is at least once accused of overreacting by their spouse while calling in sick for work with a mild rhinitis. Is this simply a behavioural difference between sexes? Or could it be true that men are immunologically inferior to women, and therefore experience more symptoms? It seems like a trivial question, but there is quite some research available about the possible sex differences in our immune system.
Mice studies show that immunity against Influenza viruses is higher in female mice than in males . This led to the idea that sex-dependent hormones play a role in the immune response. This idea is supported by the fact that pregnant women are susceptible to various infectious diseases. We know that during pregnancy there are a lot of (sex dependent) hormone fluctuations. Furthermore, an in-vitro study showed that oestradiol decreases influenza titres. Human nasal epithelial cell cultures were exposed to oestradiol or select estrogen receptor modulators and then infected with Influenza A virus, and virus titres decreased only in the samples of female donors .
These findings may lead to the conclusion that there are sex differences in our immune system. Unfortunately, mice studies and in-vitro studies cannot be simply translated to clinical practice. Researchers from the Radboud University Medical Center did a small experiment with endotoxins on 30 healthy volunteers. They found that the vascular reactivity to norepinephrine was diminished in men while they were administered endotoxins [6, 7]. This could lead to severe sepsis and septic shock, serious medical complications. I do think it is too soon to draw a conclusion, blaming the shortage of translational evidence. However, next time my boyfriend complains about flu-like symptoms, I might be a little less accusing.
* This brief message was rectified on 06-12-2018 due to the use of inaccurate references.
 Sue, K. The science behind “man flu”. Bmj 359, j5560 (2017).
 Bouma, J. Ja, mannen stellen zich aan. Nou en? in, Vol. 2018 (nrc.nl, 2018).
 Keulemans, M. ‘Best zware mannengriep’ verdampt onder experts toch weer tot aanstelleritis. in, Vol. 2018 (Volkskrant.nl, 2018).
 Lorenzo, M.E., et al. Antibody responses and cross protection against lethal influenza A viruses differ between the sexes in C57BL/6 mice. Vaccine 29, 9246-9255 (2011).
 Peretz, J., et al. Estrogenic compounds reduce influenza A virus replication in primary human nasal epithelial cells derived from female, but not male, donors. Am J Physiol Lung Cell Mol Physiol 310, L415-425 (2016).
 Van Eijk, L.T., et al. Gender differences in the innate immune response and vascular reactivity following the administration of endotoxin to human volunteers. Crit Care Med 35, 1464-1469 (2007).
 Van Eijk, L.T. & Pickkers, P. Man flu: less inflammation but more consequences in men than women. Bmj 360, k439 (2018).