In men, high testosterone can mean weakened immune response, Stanford study finds

Scientists at the Stanford University School of Medicine have linked high testosterone levels in men to a poor immune response to an influenza vaccine.

In a study to be published online Dec. 23 in the Proceedings of the National Academy of Sciences, the investigators show that 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.

In the study, women had a generally 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 has long 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 don't respond as strongly as women's to vaccinations against influenza, yellow fever, measles, hepatitis and many other diseases. The new 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 in animals and in cell-culture experiments 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 directly chill immune response; rather, it seems to interact with a set of genes in a way that damps that response, said the study's senior author, Mark Davis, PhD, professor of microbiology and immunology and director of Stanford's Institute for Immunity, Transplantation and Infection.

"This is the first study to show an explicit correlation between testosterone levels, gene expression and immune responsiveness in humans," said Davis, who is also the Burt and Marion Avery Family Professor of Immunology. "It could be food for thought to all the testosterone-supplement takers out there."

The scientists took advantage of ongoing longitudinal research at Stanford. Since 2008, the research participants, who span a broad range of ages, have been getting blood drawn before and after receiving annual influenza vaccines. Many have returned year after year for their annual flu shots and associated blood draws. The participants' samples are analyzed at Stanford's Human Immune Monitoring Core, a distributed center deploying state-of-the-art instrumentation and expertise, for tens of thousands of variables, including circulating levels of numerous immune-signaling proteins; counts of various blood-cell subtypes; and the degree to which each of the roughly 22,000 genes in a participant's circulating immune cells is active or inactive.