When trans men receive testosterone therapy, their bodies begin to resemble those of CIS men in many ways - including their immune systems. This is what a study published today in Nature 1 so far Gender -confirming hormone therapy (Gaht) has an impact on the immune system over time.

The results provide urgently needed insights and could explain why men tend to be more susceptible to viral infections than women and women are often more susceptible to autoimmune diseases.

The study is important because doctors want the gaht "of course safe," says co-author Mats Holmberg, endocrinologist at the Karolinska Institute in Stockholm, which offers gender-confirming care. It is a step towards the possibility to give the best possible treatment, says Holmberg.

an immunological balance?

During their study, Holmberg and his colleagues collected blood from 23 trans men (who were assigned female at birth, but were looking for a male gaht) at three times: Before they started with the Gaht, three months after the start of treatment and one year after the start of treatment. Over time, the researchers observed a shift in the immune response of the participants, by a type that is characterized by high concentrations of immune signs called type I interferone, which have specialized in the fight against viral infections, into one in which an abundance of an inflammatory protein called tumor necrosis factor (TNF), which connects with muscle growth is.

The news here is that sex hormones seem to cross immunological paths, says study mitar Petter Brodin, a pediatric immunologist at the Karolinska Institute. When the testosterone level increases and the estrogen level decreases, it seems as if the immune system goes through an equilibrium, Brodin adds.

"This is a very interesting new knowledge that will trigger a lot of research," says Marcus Altfeld, an immunologist at the University Hospital Hamburg-Eppendorf in Germany. In particular, Altfeld wants to understand whether rising TNF levels directly reduce the amount of type i interferons or whether testosterone convey both effects independently.

illness effects

The researchers find that their findings reflect the real susceptibility to infection and illness at the molecular level. For example, men who were infected with the Coronavirus Sars-Cov-2 during the early days of COVID-19-Pandemie Women . This makes sense, says Brodin, since women typically have high concentrations of type I interferons that help them ward off infections.

On the other hand, women develop more persistent covid-19 than men-about 76% more often, according to a study 2 . This could be due to the fact that persistent Covid-19 is similar to autoimmune diseases, some of which are associated with an overactivation of the type I interferon system.

other research also indicate this direction. A pre-published study 3

But hormones are probably not the whole story when it comes to differences in susceptibility to covid-19 or other diseases, researchers say. The X-chromosome-typically two copies of women and men also pays attention, says Sabra Klein, immunologist at John's Hopkins University in Baltimore, Maryland. The X-chromosome is rich in genes that are connected to the immune system, so it is likely that the attribution of gender differences in the results of Covid-19 only "simplifies something that is more complex," she says.

autoimmune risk

Trans men do not have to be too concerned that testosterone therapy increases their risk of viral infections. "Most normal infections are common in both genders," says Altfeld, and people recover from it. Autoimmune diseases, on the other hand, can be serious, and Holmberg fears that estrog therapy that reduces testosterone could increase the risk of developing these diseases.

But the study did not directly examine estrogen treatment or security. Klein believes that it is still too early to say whether the connection between autoimmune diseases and gaht should be taken into account. "These are small sample sizes," she says - 23 people are not much. "This indicates the need for further research."

Some doctors already warn their patients of the context. Altfeld, who examines the effects of the gaht on the immune system, says that he works with doctors who inform the trans women that estrogen treatment is associated with a risk of developing an autoimmune disease. The potential disadvantage is "known in the community," he says.

But not all of them have such well -informed doctors. It is "really difficult" to find a medical provider that specializes in several disciplines such as immunology and gender-confirming care and can treat "intersectional needs", says Jamie, a transmasculin person (assigned to the boring as female, but identifying with masculinity) who suffers from an autoimmune disease called Sjögren-Syndrome and To be identified pseudonym, since not everyone knows about their gender identity in their lives.

Jamie decided both for testosterone therapy for the gender confirmation and the treatment of the Sjögren syndrome-a measure that she took due to her own studies in scientific literature instead of the council of a doctor. Since then, Jamie has exchanged testosterone therapy for an immunosuppressant called Adalimumab (sold as a humira) to improve her health. Adalimumab inhibits TNF, which is increased in people with Sjögren syndrome. Holmberg and Brodin's work let Jamie think about whether the return to testosterone therapy would reduce the effectiveness of the Adalimumab it took because their TNF levels could increase. "My God, I wish there were studies to know how to know how the interactions work instead of just having to advise you," she says.