• Females may be more likely to experience side effects from flu vaccines than males, new research says.
• Female vaccine recipients reported more injection-site reactions, systemic reactions, and severe reactions from flu shots, researchers said.
• Though the new study didn't examine why females may fare worse with vaccine side effects, some working theories point to genetic and hormonal differences in females that may affect immune response.

Females may be more likely to experience flu vaccine side effects—including fever, headache, and muscle aches—compared to males, researchers say, and they should be made aware of these increased risks.

The news comes from a new meta-analysis published in the Journal of Epidemiology & Community Health, in which researchers compared adverse reactions to flu vaccines in males versus females. Overall, females were likelier to experience both injection-site reactions, as well as systemic reactions.

Although it’s been recognized that immune responses and adverse reactions to vaccines differ between females and males, most studies don’t specifically call out those differences. The lack of data on the differences in reactions also potentially puts females at risk and may increase their vaccine hesitancy.

Here’s what to know about the sex differences in flu vaccine reactions and why these findings are important to public health.

Women Have a Higher Risk of Reactions After Flu Shot

For the study, researchers analyzed data from 18 different studies which included more than 34,000 adults. They found a higher risk of injection-site reactions (pain, swelling, or redness) in females compared to males, with females over 65 having the highest risk.

Females were also more likely to experience systemic vaccine reactions (fever, headache, or muscle aches), and were likelier to experience severe reactions from the shots, as well.

According to the study authors, the absolute risk increase is an estimated 115 additional injection-site reactions in females versus males among 1,000 people who received vaccines and 75 additional cases of systemic reactions.

The study did have some limitations: Researchers said that the adverse effects were all self-reported and that the reported adverse effects reflect both sex and gender—sex refers to biological and physiological characteristics of males and females, while gender refers to role and behavior of men and women.

Study authors noted that women may also be more likely than men to report side effects or other health events.

“There have been other pieces of literature that have concluded something similar,” William Schaffner, MD, an infectious disease specialist and professor at the Vanderbilt University School of Medicine, told Health.

A study published last year by the Centers for Disease Control and Prevention (CDC) found that, of 6,994 people who reported side effects of the COVID-19 vaccine, 79.1% of them were women.

A cross-sectional study of 843 healthcare workers published last year found that around 65% of men had some kind of reaction to the COVID-19 vaccine, compared to 77% of women. A 2021 analysis of 41 research articles on COVID-19 vaccines also found that women had a higher risk of side effects than men.

Despite this difference, “results for vaccination safety are often not presented by sex despite the fact that the risk of adverse events following vaccines could vary between males and females,” Marilou Kiely, PhD, lead author of the latest study and a researcher in the department of Microbiology, Infectiology, Immunology & Pediatrics at the University of Montreal, told Health.

Theories Regarding Sex Differences in Vaccine Reactions

The study didn’t explore why females are likelier to experience side effects—it simply found an association. However, there are some theories behind why females may be more likely to have vaccine reactions than males.

“Genetic and hormonal differences between females and males influence the immune responses to infections and vaccination,” Kiely said, noting that women “usually develop a greater inflammatory response” after they’re vaccinated, which can lead to side effects.

Estrogen specifically may be a larger factor. “It may be that estrogen is more involved in the immune system than we know,” Shaffner said. “But this hasn’t been studied carefully.”

Ultimately, there are still a lot of unknowns.

“It’s likely that there are many sex differences that we don’t know about or don’t understand when it comes to drug and vaccine administration,” Jamie Alan, RPh, PharmD, PhD, an associate professor of pharmacology and toxicology at Michigan State University, told Health. “Unfortunately, sex differences are poorly studied and poorly understood.”