High testosterone levels linked to poor response to flu vaccine

Researchers say they have linked high testosterone levels in men to a poor immune response to an influenza vaccine.

In a recent study published online in the Proceedings of the National Academy of Sciences, the investigators showed 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.

“This is the first study to show an explicit correlation between testosterone levels, gene expression, and immune responsiveness in humans. It could be food for thought to all the testosterone supplement takers out there,” said senior author Mark Davis, PhD, of Stanford University’s Institute for Immunity, Transplantation and Infection, Stanford, CA.

In the longitudinal study that started in 2008, the research participants, who span a broad range of ages, have been getting blood drawn before and after receiving annual influenza vaccines. The participants’ samples are analyzed at Stanford’s Human Immune Monitoring Core 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.

Analysis of samples from 53 women and 34 men showed that, on average, women had significantly stronger antibody responses to the influenza vaccine, consistent with other studies. The women also showed higher average pre-vaccination blood levels of pro-inflammatory immune-signaling proteins, as earlier studies have found. But pre-vaccination levels of those proteins in a particular woman’s blood didn’t significantly predict the degree of her post-vaccination antibody response.

The analysis also showed that, in men, elevated activity of a particular set of genes that tend to turn on and off at the same time was associated with a weakened antibody response to the vaccine. The same gene cluster’s activity levels didn’t track closely with antibody response in women.

Previous studies have shown that some of the constituent genes of this multi-gene cluster (known as Module 52) are involved in immune regulation and that activation of the module is somehow boosted by testosterone.

The authors looked directly at testosterone levels in their male subjects. They separated the 34 men into two groups-those whose circulating levels of testosterone in its bioactive form were above the median level, and those with below-median levels of the hormone. They found that, in the high-testosterone men, high-activation levels of Module 52 genes correlated with reduced post-vaccination antibody levels. In the low-testosterone men-as in women-activation levels of Module 52 genes bore no significant relationship to the amount of antibodies produced as a result of the influenza vaccine.