Tuesday, February 27, 2024


“You may choose to look the other way, but you can never say again that you did not know.”

— William Wilberforce

Immune Response May Highlight Gender Differences

woman and man laying down

woman and man laying downStory Highlights

  • “Man flu” is an often-belittled concept that men tend to suffer more severely than women from influenza and other respiratory illnesses.
  • New research suggests that there may be a hormonal basis for the gender differences in immune response to influenza and influenza-like illness.
  • Estrogen hormones, particularly estradiol, appear to increase women’s immune response to both natural viruses and vaccination, while male testosterone suppresses the immune response.

The designation “man flu” began as a joke to acknowledge the eye-rolling observation among women that the men in their lives consistently complain more and feel and act sicker than they do, given the same diagnosis. New research, however, may vindicate males: gender differences in immune system responses may actually provide a benefit for women and explain the more severe symptoms experienced by men.1

Tired of “being accused of over-reacting,” Kyle Sue, MD, assistant professor of family medicine at Memorial University of Newfoundland in Canada, searched for scientific evidence to support a possible gender difference in response to illness. He also wanted to determine whether there could be an evolutionary explanation for the difference.

Animal Studies Reflect Gender Differences

Dr. Sue reported that a substantial number of animal studies have previously shown that females mount a more robust response to both natural pathogens and to vaccination than males.2 He added that several sources suggest that the estrogen hormone estradiol may be responsible for the different reactions, either by reducing pathologic response to viral exposure or by increasing the immunologic response to the virus.

Sue admitted that mouse studies are not conclusive evidence of gender differences in humans, but he quoted several sources indicating differences in humans as well. For example, data out of Hong Kong showed that more adult men than women were hospitalized for influenza, and a U.S. study showed that men had a higher risk of dying from influenza than age-matched women. Even the World Health Organization (WHO) lists gender as a factor for consideration in evaluating influenza data.

The Gender Gap: Estrogen vs Testosterone

The sex hormones may have a significant role to play in immunologic responses in general. Sue points out that women have been shown to have a more pronounced local and systemic reactions to flu vaccination than men, and some researchers have suggested it is linked to the influence of estrogen. Conversely, the male hormone testosterone has been linked to a “down-regulation” of the immune response. This phenomenon is not limited to cases of influenza, but appears across respiratory illnesses in general. Quoting a non-scientific survey, Sue and his colleagues reported that women tend to take one and a half days to recover from a respiratory illness, while men need an average of three days.

Looking at the differences between male and female responses to illness from an evolutionary standpoint, Sue speculates that the traditionally male roles of aggression and dominance supported by testosterone may have trumped the need to spend “metabolic resources” building a strong immune system, perhaps because males were more likely to die from battle or trauma. Unsaid but just as likely, women would have needed the self-protection of a strong immune system to raise and protect the offspring.

Other Factors Contribute to Differences

Sabra L. Klein, PhD, associate professor at Johns Hopkins University Bloomberg School of Public Health, applauded Sue’s shedding a light on gender differences in health but warns that factors other than hormones must be taken into consideration.3 She pointed out, for example, that in societies where males are more valued than females, boys and men tend to be hospitalized more frequently than girls or women.

Dr. Klein also stressed that age plays a very important role in our immunologic responses to influenza: Very young boys and men over age 65 require hospitalization more than men in their prime. She also stresses that women of reproductive age experience more severe flu symptoms, “in part because influenza is worse for pregnant women but also because women develop higher—almost excessive—inflammatory responses to flu,”3 although that also supports the hormone theory.

Noting that further research is needed to evaluate the scientific basis of “man flu,” Sue suggests—perhaps facetiously—that future studies might include one in which “men are infected with a respiratory virus, then subjected to rigorous research conditions in which all their requests are met by a healthy designated caregiver or they are left to fend for themselves.”1

In what appears to be a further effort to take men off the hook for “man flu” behaviors, Sue also suggests that women may be to blame for picking men to mate with who are high in testosterone but have weak immune function. Sue urged research looking into whether “men with robust immune systems are less successful at mating compared with those with weaker immune systems and correspondingly higher testosterone. In other words, can the blame for man flu be shifted to the people who select these men as sexual partners rather than the men themselves?”1


2 Responses

  1. Very interesting. Testosterone tends to down-regulate immune response? Could that be one reason women suffer significantly higher rates of auto-immune diseases? Worth further research for sure.

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