The immune system is the body’s network of defenses. And, like many other functions, it also shifts when a transgender person starts gender-affirming hormone therapy. A team from Ghent University (Belgium) followed dozens of people before and after starting this treatment and observed something striking: estrogens appear to quiet part of the inflammatory signaling, while testosterone tends to turn it up.
A signaling network that also responds to hormones
Sex hormones do not only shape physical traits; they also take part in regulating the immune system. To study this precisely, the researchers analyzed blood from 30 transgender women and 30 transgender men who were starting their hormone treatment, and repeated the analysis about six months later. Cisgender men and women not taking hormones were included as a comparison group.
The work focused on two kinds of measures: high-sensitivity C-reactive protein, a classic marker of inflammation, and a broad panel of cytokines and chemokines, small proteins that coordinate the body’s defensive response.
Estrogens that quiet, testosterone that switches on
The results pointed in opposite directions. In transgender women, six months of estrogens with antiandrogen treatment significantly reduced the levels of ten cytokines (including CCL2, CCL7, CXCL9, CXCL10 and IL15), while only one, IL7, increased. In transgender men, by contrast, testosterone raised eight factors involved in the immune response (such as CCL2, CCL7, CCL13 and MMP1).
The classic marker of inflammation, C-reactive protein, barely changed in a clinically relevant way. The spotlight fell on the cytokines: more discreet, less well known, but essential for immune cells to communicate with one another.
What does this “change of direction” mean?
For the authors, this opposite pattern reflects a direct influence of sex hormones on immunity, and opens a path to understanding why some inflammatory and autoimmune diseases affect men and women differently. If estrogens silence part of that signaling and testosterone amplifies it, gender-affirming hormone therapy could modulate that balance in each person.
It is worth remembering the limits of the study. It is a small sample —60 transgender people—, follow-up is limited to six months, and the authors warn that the real clinical consequences and the exact mechanisms involved are still unknown. More research will be needed to translate these signals into concrete health benefits.
What it adds to transgender care
Beyond the biological data, the finding reinforces an idea already solid in gender medicine: gender-affirming hormone therapy is not a superficial or “merely aesthetic” change, but a process with measurable effects across the whole body, including immune defense. Understanding that footprint better can help personalize treatment and monitor the health of transgender people with a more complete view.
Source: The Journal of Clinical Endocrinology & Metabolism, 2026. doi:10.1210/clinem/dgag141
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