High levels weaken immune response.

• Position: Testosterone

Men with relatively high amounts of circulating testosterone benefit less, as measured by a boost in protective antibodies after vaccination against influenza, than do men with lower testosterone levels and women, according to a study at Stanford University, Palo Alto, Calif.

In the study, women generally had a stronger antibody response to the vaccine than men, but the average response mounted by men with relatively low testosterone levels was more or less equivalent to that of women.

It long has been known that, for reasons that are not clear, men are more susceptible to bacterial, viral, fungal, and parasitic infection than women are, and that men's immune systems do not respond as strongly as women's to vaccinations against influenza, yellow fever, measles, hepatitis, and many other diseases. The study may explain why this is the case.

Women are known to have, on average, higher blood levels of signaling proteins that immune cells pass back and forth to jump-start inflammation, a key component of immune-system activation. Furthermore, previous research has established that testosterone has anti-inflammatory properties, suggesting a possible interaction between the male sex hormone and immune response. However, the new study found no connection between circulating levels of pro-inflammatory proteins and responsiveness to the flu vaccine--nor does testosterone appear to chill immune response directly. Rather, it seems to interact with a set of genes in a way that dampens that response, says senior author Mark Davis, professor of microbiology and immunology and director of the Institute for Immunity, Transplantation and Infection.

"This is the first study to show an explicit correlation among testosterone levels, gene expression, and immune responsiveness in humans," stresses Davis. "It could be food for thought to all the...