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In-Depth: Why women have more vaccine side effects than men

Sex hormones, chromosomes play a role
Posted at 10:04 AM, Apr 29, 2021
and last updated 2021-04-29 13:04:12-04

SAN DIEGO (KGTV) — As more Americans get immunized with the COVID-19 vaccines, there’s a clear trend emerging: women are experiencing more severe side effects.

Women submitted 78.7 percent of the side effect reports to the Centers for Disease Control and Prevention during the first month of vaccination from Dec. 14 to Jan. 18, the most recent data available. Women got 61.2 percent of the doses in that span.

“I felt like I got hit by a truck,” said Emily Vaccarezza, who said she experienced fever, soreness, and a headache after her second Moderna dose.

She warned her boyfriend, Michael Stewart, to expect similar symptoms the day after his second shot. “I was pleasantly surprised to find that I experienced none of those and was mostly just tired,” he said.

During the first month, women experienced 95 percent of the severe allergic reactions to the mRNA vaccines: 63 of the 66 cases.

And the first 15 cases of severe blood clots with low platelet counts associated with the Johnson and Johnson vaccine were all in women. (This week, the CDC said it was investigating one case involving a man.)

“We've actually known this for a while from studying other vaccines that women do experience more side effects than men overall,” said Dr. Abisola Olulade, a family medicine physician at Sharp Rees-Stealy Medical Group.

This pattern plays out with vaccines against measles, mumps and rubella, yellow fever, Japanese encephalitis, and influenza. In the case of the flu vaccine, women consistently report more side effects than men, sometimes at double or triple the rate.

“There are a lot of potential reasons for this, and one of them is estrogen versus testosterone,” said Dr. Olulade.

Scientists have learned the hormone estrogen makes immune cells work harder, causing more inflammation. The presence of testosterone suppresses this cellular behavior.

“Women have higher levels of estrogen, and that leads to a stronger immune response, and androgens, or testosterone, leads to a weaker immune response,” said Dr. Olulade.

Differences in the immune response are more pronounced after puberty when individuals have higher levels of these hormones, supporting evidence for the theory that these hormones play an important role, Olulade said.

Researchers suspect DNA is also a factor. Women have two X chromosomes. Men have an X and a Y chromosome. That X chromosome contains the code for some of the most important immune-related genes.

“Having that extra X chromosome does lead to increased proteins that are involved in the immune response,” Olulade said.

These sex-based differences aren’t unique to humans. In birds, lizards, and other mammals, females have stronger immune systems than males.

When it’s too strong, the immune system can attack itself; 80 percent of autoimmune diseases occur in women. But it also means women are better protected overall.

“What seems like a downside initially actually is helpful later on,” Olulade said.

Women produce more antibodies after they get a vaccine, twice as many in the case of the flu vaccine, and the coronavirus has hit men much harder. Men who get COVID-19 require intensive care at nearly three times the rate of women.

So remember, Dr. Olulade says, those mild vaccine side effects are a sign the shots are working -- probably a little better in women than men.