London scientists have discovered that sex hormones can impact the immune system in men and women, making them experience diseases differently.
Researchers at Imperial College London and the Karolinska Institutet in Sweden said the discovery could lead to more targeted treatments.
It is well known that men and women experience more or less severe diseases. Men are known to have a greater risk of acute first-time Covid infection, while women have a greater risk of long Covid.
But until now, scientists have not been able to unpick the reason for the disparity in health outcomes.
For the study, researchers monitored 23 transgender men who had been registered female at birth and were undergoing testosterone treatment.
The team collected blood samples from patients before treatment, and then after three months and one year of testosterone treatment.
Analysis found that several key elements of the immune system had changed following treatment.
To test whether the observed changes were directly due to the increase in testosterone or indirectly from reduced oestrogen, the team analysed blood from 11 female donors.
Samples were treated with receptor blockers to show that the effect was directly due to testosterone signalling, rather than loss of oestradiol-signaling.
They found that increased testosterone and reduced oestrogen levels alter the balance between two crucial immune signalling systems that have direct implications for how the immune system responds to infection and disease.
Researchers said the findings could also open up potential avenues for new, more targeted treatments for men and women, as well as leading to a better understanding of the immunological consequences of hormone therapy in trans people.
Petter Brodin, Professor of Paediatric immunology at Imperial College London, who led the work while based at the Karolinska Institutet, said: “These findings have implications for us all. For the first time, we have been able to identify which parts of a person's immune system are directly regulated by sex hormones rather than genetic sex differences.
“This could have significant impact not only on our understanding of how different diseases affect males and females differently, but also to develop new treatments which could help in everything from immune diseases to cancer.”
He added: “We’re extremely grateful to the people who contributed to this study. Trans individuals are a hugely under-represented and under-served group in medicine. In addition to the invaluable immunological insights we’ve uncovered here, the involvement of this small group of people will enable us to gain deeper insights which may help the long-term health of trans people around the world.”
