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Transgender men who undergo hormone therapy as part of their gender-affirming care may experience changes in their immune system, according to a recent study published in Nature. The study, conducted by scientists in Sweden, focused on a small group of transgender men who were assigned female at birth and were taking testosterone. The researchers found that these individuals exhibited alterations in immune cell pathways involved in responding to viral infections and inflammation.

Understanding Immune System Differences

The immune systems of men and women have long been known to have distinct differences. Men are generally more susceptible to viral infections, such as COVID and influenza, while women tend to have stronger responses to viruses but are more prone to autoimmune diseases like lupus. However, the exact reasons for these differences are not fully understood. The study on transgender men sheds some light on how hormones, specifically testosterone, may play a role in shaping immune responses.

According to Dawn Newcomb, an assistant professor of medicine at Vanderbilt University Medical Center, the study’s findings align with previous research on how sex hormones influence immune function. The results suggest that testosterone may dampen antiviral responses while promoting inflammatory responses, similar to the immune activity observed in cisgender men. This indicates that hormone levels play a significant role in shaping immune system function.

Impact of Testosterone Therapy

The study involved 23 transgender men between the ages of 18 and 37 who were undergoing testosterone therapy. Blood samples were taken before the participants started hormone treatment and again at three and 12 months post-treatment to analyze changes in immune cells and signaling proteins. Within three months of starting testosterone therapy, the participants’ testosterone levels reached typical ranges for cisgender men, while their estradiol and progesterone levels decreased. After 12 months, the participants showed a decrease in the immune response involving type I interferon, a protein used to fight viral infections, and an increase in the TNF signaling pathway associated with fighting bacterial infections through inflammation.

While the study’s findings are significant, it is important to note that the sample size was small. Newcomb emphasizes that sex hormones are likely just one mechanism influencing immune development, alongside genetics and epigenetics. Further research with larger sample sizes and longer follow-up periods is needed to fully understand the implications of hormone therapy on immune function in transgender individuals.

Implications for Health

The results of the study may have implications for the health of transgender men undergoing masculinizing hormone therapy. While the study did not suggest increased susceptibility to infections, it did reveal changes in immune profiles that align more closely with cisgender men. Petter Brodin, a professor of pediatric immunology at the Karolinska Institute in Stockholm and co-author of the study, emphasizes the importance of monitoring all patients receiving hormone therapy to ensure there are no unintended health consequences. This caution extends to individuals taking hormone therapies for various reasons, not just gender-affirming care.

Brodin suggests that continued research and monitoring of individuals undergoing hormone therapy are essential to understand the long-term effects on immune function. Nils Landegren, a physician and assistant professor at Uppsala University in Sweden, also highlights the need for larger studies and longer follow-up periods to assess the risk factors associated with hormone therapy on immune function. Landegren is leading a study on transgender women taking female sex hormones to further explore the effects of hormone therapy on immune function.

Evolutionary Factors

The differences in immune function between men and women may be rooted in evolutionary factors related to reproduction. Women invest significant resources in reproduction and pregnancy, leading to a stronger antiviral immune response to protect fetuses from infection. However, an overly strong inflammatory response could potentially harm a fetus, indicating a delicate balance in immune function. In contrast, men prioritize muscle growth, which requires higher levels of TNF, a signaling pathway associated with fighting bacterial infections.

The immune system’s evolutionary balance between surviving infections and minimizing the risk of autoimmunity is a complex interplay influenced by various factors, including hormones and genetic predispositions. Understanding how these factors interact and shape immune function in different populations is crucial for developing personalized healthcare approaches that account for individual differences.

In conclusion, the study on the impact of testosterone on the immune system in transgender men sheds light on the complex relationship between hormones and immune function. While more research is needed to fully understand the implications of hormone therapy on immune health, the findings highlight the importance of monitoring individuals undergoing hormone treatment for potential changes in immune profiles. By continuing to explore the interplay between hormones, genetics, and immune function, researchers can develop more effective and personalized healthcare strategies for diverse populations.