High Testosterone Levels Could Help Weaken Immune System Response

redOrbit Staff & Wire Reports – Your Universe Online

Research published online Monday in the journal Proceedings of the National Academy of Sciences has reportedly uncovered a link between high testosterone levels in men and a weakened immune response to influenza vaccines.

In the study, senior author Dr. Mark Davis of the Stanford University School of Medicine and his colleagues showed that men with relatively high amounts of circulating testosterone received less of a benefit from flu shots than men with lower testosterone levels and with women.

The high-testosterone men experienced less of a boost in protective antibodies following vaccination against influenza than the other groups, they said. Women were found to have a generally stronger antibody response to the vaccine than all men, but males with low testosterone levels experienced benefits nearly equal to females.

The researchers note that it has long been known that men are more susceptible to bacterial, fungal, parasitic and viral infections than women, and that their immune systems do not respond as well to vaccinations, but the reasons remained unclear. The new study could shed new light on the causes of this susceptibility.

Females tend to have higher blood levels of the proteins passed back and forth by immune cells to kick-start inflammation, an essential component of immune-system activation. In addition, previous studies in animals and cell-culture experiments have established that the male sex hormone has anti-inflammatory properties.

According to Davis, the new study discovered no link between circulating levels of pro-inflammatory proteins and responsiveness to the flu vaccine. Likewise, the investigators found no evidence that testosterone directly impacts immune system response. Instead, it appears to interact with a set of genes to inhibit that response.

“This is the first study to show an explicit correlation between testosterone levels, gene expression and immune responsiveness in humans,” he said. “It could be food for thought to all the testosterone-supplement takers out there.”

“Most studies don’t report on sex differences, a major determinant of variation in immune response,” added lead author Dr. David Furman. Furman, a research associate working alongside Davis, and their colleagues analyzed blood samples from 53 women and 34 men in their research and found that the females has significantly stronger antibody responses to the flu vaccine.

The results were consistent with previous work in the field, the researchers said. Women also tended to have higher pre-vaccination blood levels of pro-inflammatory immune-signaling proteins, but those levels were not a significant indicator of how successful their post-vaccination antibody response would be.

Furthermore, the research showed that elevated activity of a set of genes known as Module 52, which tended to switch on and off at the same time, was linked to a weakened antibody response to the vaccine in men. This same gene cluster’s activity levels were not found to track closely with antibody response in women, though.

In order to look more closely at this phenomenon, Davis, Furman and their associates separated the 34 male patients into two groups: those whose circulating levels of testosterone in its bioactive form were above the median level, and those with below-median hormone levels. As it turned out, high-testosterone men with high Module 52 gene activation levels correlated with reduced post-vaccination antibody levels.

“Additional analyses showed that testosterone reduces levels of certain transcription factors (regulatory proteins) that ordinarily prevent Module 52 genes from ‘turning on.’ In other words, higher testosterone levels result in more Module 52 expression,” Stanford University Medical Center explained in a statement.

“Several Module 52 genes have known immune-system connections; activation of one of these genes, for example, results in the accelerated differentiation of cells whose job it is to suppress, rather than foster, immune response,” it added. “These connections make the interactions of the genes with testosterone an intriguing target of further exploration by immunologists, physiologists and drug researchers.”