This is regardless of age or vaccine type, pooled data analysis suggests
Communicating these differences may help curb vaccine hesitancy, say the researchers

Women may be at greater risk than men of injection site and systemic reactions to the seasonal flu jab, regardless of age or vaccine type, finds a pooled data analysis of the available evidence, published online in the Journal of Epidemiology & Community Health.

Sex differences aren’t usually considered in vaccine programmes/policy, but transparent communication of these differences might increase trust in vaccines and curb vaccine hesitancy, suggest the researchers.

Immune responses to vaccines and side effects may differ between the sexes, but the evidence is somewhat limited as vaccination outcomes aren’t generally stratified and reported by sex, say the researchers.

To explore this further, they drew on data from 18 comparative clinical trials (phase III) of seasonal flu vaccination, involving 34,343 adults, and carried out between 2010 and 2018. They pooled the trial results, looking at potential sex differences by age:18-64 and 65+. 

They looked particularly for anticipated injection site and systemic reactions assessed within 7 days of vaccination, as well as specific reactions for each included study—pain, redness, fever, headache and muscle aches (myalgia). And they included other health outcomes assessed 3 to 4 weeks afterwards as well as any serious outcomes reported during the entire study period.

The risk of an injection site reaction was higher in women than it was in men for both younger (29%) and older (43%) participants. Women were also at heightened risk of systemic reactions, regardless of age: 25% higher for younger participants and 27% higher for older participants. 

The risk of a severe reaction was twice as high in women as it was in men, and about 50% higher in younger participants for systemic reactions. No differences were observed for vaccine type.

The results indicate an absolute increase in risk among women of 115 extra cases/1000 vaccinees of injection site reactions, and 74 extra cases/per 1000 vaccinees of systemic reactions. 

However, the quality of evidence was deemed low for injection site reactions and moderate for systemic reactions, point out the researchers, who acknowledge that gender—the roles, behaviour activities, and attributes associated with men and women—might have influenced outcomes, given that women are more likely to report health issues.

“Data from [randomised controlled trials] suggest that most reactions following influenza vaccinations are mild, self-limited, and rarely serious. However, as the experience of an adverse event could be a barrier for subsequent vaccinations, limiting the impact of safety concerns on vaccination programme success is critical, especially for the influenza vaccine which is needed annually,” they suggest. 

“Transparent communication regarding the increased risk for females would potentially help sustain long-term trust in health authorities and vaccines,” they conclude. 


Notes for editors
 Sex differences in adverse events following seasonal influenza vaccines: a meta-analysis of randomised controlled trials doi 10.1136/jech-2023-220781
Journal: Journal of Epidemiology & Community Health

Funding: Canadian Institutes of Health Research

Academy of Medical Sciences Press Release Labelling system 

Externally peer reviewed? Yes
Evidence type: Meta analysis
Subjects: People