Men: the weaker sex

a really, really important article was just published in the holiday edition of the BMJ, exploring the science behind "man flu"​​, which the Oxford English dictionary defines as: "a cold or similar minor ailment as experienced by a man who is regarded as exaggerating the severity of the symptoms" (see https://en.oxforddictionaries.com/definition/man_flu ). this BMJ article suggests that it is not simply that men are wimpier, but they actually may have a weaker immune system, and that there may be an evolutionary basis for this (see http://www.bmj.com/content/359/bmj.j5560 , or doi: 10.1136/bmj.j5560). my minimally detailed search has suggested that this "man flu" thing is actually sort of real and not a joke (though not having heard of it before, i must admit that i did suspect otherwise, and was especially doubtful that there would be an Oxford English dictionary definition of it....).

Details:

--female mice have greater immune responses vs. male mice. 

--this mouse difference may be attributable to estrogen, which limits the pathology of pulmonary pathogens (including influenza A) by reducing the production of proinflammatory cytokines and chemokines (see Robinson DP. J Virol 2014; 88(9): 4711), though another study suggested that stress/cortisol had a role (female mice had less rapid interleukin response to influenza A than males, but there was more proinflammatory cytokine production in both male and female mice in stressful situations)

--a cell culture study of human nasal mucosa (where influenza virus replicates) found that infection with seasonal influenza A, then exposure to various estrogenic compounds (estradiol, SERMs), led to decreased influenza A titers and downregulated cell metabolic processes but only in females, and this effect was reversed by estrogen receptor antagonists

--a study in premenopausal women given rhinovirus found that they had a stronger immune response than men, but this was not found in postmenopausal women

--there are some epidemiologic data confirming the male/female difference:

    --a Hong Kong study during seasonal influenza found that men had higher risk of hospital admission

    ​--a US study found that men had a higher influenza mortality than women

--there are data that women have a more robust antibody response to vaccination than men

    --women have more local and systemic reactions to the vaccine

    --men with higher testosterone levels have lower antibody response to vaccine (ie, testosterone itself may be immunosuppressive, also found in animal studies)

    ​--men tend to have higher mortality from other acute respiratory diseases

    ​--and studies have found (contrary to the Oxford dictionary exhortation that men simply "exaggerate” the symptoms) that women were more likely to cut down on activities in response to one viral respiratory symptom than men

    --and, an unscientific popular magazine survey found that men take an average of 3 days to recover from a respiratory virus vs 1.5 days in women

Commentary:

--so, sounds legit....

--however, the human studies above do have some risk of bias: eg, men tend to smoke more, perhaps have more exposure to environmental/occupational chemicals, are less likely to be involved in preventative care (or any health care, for that matter)

--women, of course, do have some fundamental immunologic difference: there is certainly a period of suppressed immunologic rejection (pregnancy) of a foreign body (fetus), as well as getting more serious influenza infections during pregnancy​. Also, in general, more frequent immunologic diseases (lupus etc)

--and interesting evolutionary explanations (as with all of the explanations in medical articles, there is a tendency to find ways to explain the study findings, perhaps a bit stretched sometimes....)

    --??men have developed such aggressive behavior through testosterone, so they reproduce more, and that is evolutionarily more important than the fact that they get sicker from viruses

    --??men are more likely to die young anyway from trauma before a viral infection gets them. the "live hard, die young" hypothesis, which seems to have persisted into the present day

    ​--??it's a waste of metabolic energy to have an immune system clear viruses. the energy should be devoted to other biological processes (reproduction, growth, etc) and social processes (fighting predators)

    --??and, lying in bed or on the couch or whining for help when not fully healthy may be protective: men not in top form may be more likely to be killed by a predator

so, not sure what to add to the above.....  but enjoy the holidays

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