How Testosterone Affects the Immune System in Trans Men

How Testosterone Affects the Immune System in Trans Men

by Lewis asked.

It is known that there are significant differences between the immune systems of men and women. In general, men have Viral infections such as COVID Influenza. Women have a stronger response to the virus, Susceptibility to autoimmune diseasesfor example, lupus. But the extent to which these differences result from genetic, hormonal, or other factors is not fully understood.

A new study published Wednesday Nature, There are some clues. Scientists in Sweden studied a small group of transgender men who had been assigned female at birth and were taking testosterone as part of gender reassignment treatment. The researchers found that the participants Changes in two distinct immune cell pathways It is involved in the response to viral infections and inflammation.

“This study confirms that testosterone inhibits and weakens these antiviral responses. [known as] “It suppresses the interferon response and at the same time promotes the inflammatory response,” says Dawn Newcomb, an assistant professor of medicine at Vanderbilt University Medical Center who studies the role of sex hormones in immune function but was not involved in the paper. “These results are in close agreement with what has been previously observed in male and female cells from cisgender people. (The term cisgender, or cis, means having the gender that corresponds to the sex assigned to you at birth.)

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The study involved 23 transgender men aged 18 to 37 who were undergoing testosterone therapy. The researchers took blood samples from the participants before they started hormone therapy, and then again three and 12 months later to look for changes in various immune cells and signaling proteins.

Within three months, most transgender men's testosterone levels fell into the normal range for cisgender men, and estradiol (the most potent estrogen produced by the body) and progesterone levels decreased. Twelve months after starting hormone therapy, participants showed a decrease in immune responses, including proteins called type I interferon, which the body uses to fight viral infections. At the same time, they showed an increase in signaling pathways, including tumor necrosis factor (TNF), which is typically used to fight bacterial infections through inflammation. These patterns were somewhat similar, though not exactly the same, to the immune activity seen in cisgender men.

While this is just one study, the findings could have implications for the health of transgender men undergoing masculinizing hormone therapy. “We cannot say that these individuals are more susceptible to infections or other conditions, but we can say that their immune profile is altered in a way that is more similar to that of men,” said Dr. [cisgender] “We see similar symptoms in men,” says Petter Brodin, professor of paediatric immunology at the Karolinska Institutet in Stockholm and co-author of the study.

To determine how much of this effect was related to increased testosterone and decreased estrogen, the researchers also drew blood from healthy cisgender female donors and exposed them to testosterone or estrogen blockers. They then measured the resulting immune changes and found that testosterone was directly involved in the TNF response. Type I interferon responses were also influenced by testosterone, although previous research has suggested that estrogen may also play a role.

Newcomb noted that the study's small number of participants is a limitation. “I think it's important to understand. [that sex hormones are] “There's probably one mechanism at work, but not the only mechanism,” she added. Genetics and epigenetics (changes in gene activity) also likely influence immune development.

Brodin would like to see better monitoring of all patients taking hormone therapy, whether for gender-affirming treatment or other reasons, such as estrogen or testosterone supplementation for cisgender men and women. “We should be urging caution among people taking hormone therapy for whatever reason,” he says, “and making sure we follow up to make sure we're not having unintended health effects.”

Study co-author Nils Landegren, a physician and assistant professor at Uppsala University in Sweden, who studies immunity, agrees that more research is needed: “To draw conclusions about the risk for these individuals, we need to gather information from these individuals about actual disease outcomes. This will require much larger numbers and longer follow-up.”Landegren is currently leading a study of transgender women who take female hormones to understand how that kind of treatment affects immune function.

So why do gender differences in immune function exist in the first place? One possible answer has to do with the fact that female bodies devote more resources to reproduction and pregnancy. Women may develop stronger antiviral immune responses to protect their fetuses from infection, but they can’t mount a strong inflammatory response, which could harm the fetus. Furthermore, high TNF levels have been shown to lead to embryo implantation failure and miscarriage. In contrast, male bodies play a much smaller role in reproduction, and may prioritize muscle growth, which has higher TNF levels.

“Our immune system and how it was shaped during evolution is determined by a balance between surviving infection and the risk of autoimmunity,” Lundegren says. “It's interesting to see how this balance differs in women and men.”