Sex hormones containing estrogens, progesterone and testosterone can stick to the surface of immune cells and affect how they work. For example, exposure to estrogens causes immune cells to produce more antibodies in response to the flu vaccine.
In addition, testosterone appears to be “very immunosuppressive,” according to Klein. The flu vaccine tends to be less protective in men with high levels of testosterone than in men with lower levels of the sex hormone. Among other things, testosterone inhibits the body’s production of immune chemicals known as cytokines.
It is also possible that genetic differences between men and women have some impact on immunity. There are many immunity-related genes on the X chromosome, of which women have two copies and men only one. Immunologists have always believed that only one X chromosome was turned on in women and the other was inactive. However, studies show that 15 percent of genes bypass this inactivation and are more strongly expressed in women.
These strong immune responses explain why 80 percent of autoimmune diseases affect women. “Women have greater immunity, either against themselves, against a vaccine antigen, or against a virus,” Klein said.
The amount in a vaccine dose can also be important. Some studies have shown that women absorb and metabolize drugs differently than men and that they almost always require fewer doses for them to work. However, until the 1990s, many drug and vaccine clinical trials excluded women. “In the past, recommended drug doses were based on clinical trials in which the participants were men,” said Morgan.
Current clinical studies already include women. According to Klein, however, the side effects were not sufficiently differentiated or analyzed by gender in the studies of the new Covid vaccines. Nor did they test whether a lower dose might be as effective for women and cause fewer side effects.
Until she does, Klein said health professionals should talk to women about the side effects of vaccines so they don’t panic if they get them. “I think it’s useful to make women aware that they may have more side effects,” she said. “This is normal and probably reflects that his immune system is working.”