News | Gender-Affirming Hormone Therapy Reshapes the Body’s Protein Profile to Align With Gender Identity
A new study by Australia’s Murdoch Children’s Research Institute (MCRI) and the University of Melbourne found that gender-affirming hormone therapy (GAHT) can alter the body’s protein composition, bringing it closer to patterns associated with a person’s gender identity. The findings show how hormone therapy reshapes biological characteristics at the molecular level and may support personalized healthcare and long-term health management for transgender people.
The study was recently published in Nature Medicine. The researchers examined more than 5,000 plasma proteins in 40 adult transgender women before and after feminizing hormone therapy and compared them with blood samples from 55,000 cisgender women in the UK Biobank. After six months of treatment, seven of ten key sex-differentiated proteins had changed significantly in transgender women, showing patterns similar to those in cisgender women.
MCRI Associate Professor Boris Novakovic said the study is the first to clearly show that gender-affirming hormone therapy can ‘rewrite’ biological markers at the blood-protein level, bringing them more closely into alignment with gender identity.
‘We observed that the therapy not only reduced protein biomarkers related to male reproduction and fertility, but also increased proteins associated with body-fat distribution, breast development, immune function, and cardiovascular health.’
—Associate Professor Boris Novakovic, MCRI
The team also found that these changes closely resembled the physiological response to hormone replacement therapy in menopausal women. Novakovic said the finding highlights adult biological plasticity, showing that even in adulthood, the body can respond markedly to changes in sex hormone levels.
The study also noted that these protein changes may have broad effects on health risks. For example, transgender women may develop a more female-typical increased risk of allergies or autoimmune disease, while their risk of heart disease may decline.
‘These results show that our biology is adaptable. Changes in sex hormones alter not only external physical features but also health risks at the molecular level.’
—Associate Professor Boris Novakovic, MCRI
University of Melbourne Professor Ada Cheung further emphasized that the findings offer a new direction for personalized transgender healthcare.
‘By studying protein changes, we can monitor the effectiveness of gender-affirming hormone therapy and detect potential heart- or immune-related side effects early. This is an important step toward precision medicine.’
—Professor Ada Cheung, University of Melbourne
The researchers called for more detailed long-term health monitoring for people receiving gender-affirming treatment, taking both physiological changes and sex-related differences into account.
The study was jointly led by Murdoch Children’s Research Institute (MCRI) and the University of Melbourne and published as:
Nguyen, N. N. L., et al. (2025). Plasma proteome adaptations during feminizing gender-affirming hormone therapy. Nature Medicine. doi.org/10.1038/s41591-025-04023-9
News | Gender-Affirming Hormone Therapy Reshapes the Body’s Protein Profile to Align With Gender Identity
News | Gender-Affirming Hormone Therapy Reshapes the Body’s Protein Profile to Align With Gender Identity
A new study by Australia’s Murdoch Children’s Research Institute (MCRI) and the University of Melbourne found that gender-affirming hormone therapy (GAHT) can alter the body’s protein composition, bringing it closer to patterns associated with a person’s gender identity. The findings show how hormone therapy reshapes biological characteristics at the molecular level and may support personalized healthcare and long-term health management for transgender people.
The study was recently published in Nature Medicine. The researchers examined more than 5,000 plasma proteins in 40 adult transgender women before and after feminizing hormone therapy and compared them with blood samples from 55,000 cisgender women in the UK Biobank. After six months of treatment, seven of ten key sex-differentiated proteins had changed significantly in transgender women, showing patterns similar to those in cisgender women.
MCRI Associate Professor Boris Novakovic said the study is the first to clearly show that gender-affirming hormone therapy can ‘rewrite’ biological markers at the blood-protein level, bringing them more closely into alignment with gender identity.
‘We observed that the therapy not only reduced protein biomarkers related to male reproduction and fertility, but also increased proteins associated with body-fat distribution, breast development, immune function, and cardiovascular health.’
—Associate Professor Boris Novakovic, MCRI
The team also found that these changes closely resembled the physiological response to hormone replacement therapy in menopausal women. Novakovic said the finding highlights adult biological plasticity, showing that even in adulthood, the body can respond markedly to changes in sex hormone levels.
The study also noted that these protein changes may have broad effects on health risks. For example, transgender women may develop a more female-typical increased risk of allergies or autoimmune disease, while their risk of heart disease may decline.
‘These results show that our biology is adaptable. Changes in sex hormones alter not only external physical features but also health risks at the molecular level.’
—Associate Professor Boris Novakovic, MCRI
University of Melbourne Professor Ada Cheung further emphasized that the findings offer a new direction for personalized transgender healthcare.
‘By studying protein changes, we can monitor the effectiveness of gender-affirming hormone therapy and detect potential heart- or immune-related side effects early. This is an important step toward precision medicine.’
—Professor Ada Cheung, University of Melbourne
The researchers called for more detailed long-term health monitoring for people receiving gender-affirming treatment, taking both physiological changes and sex-related differences into account.
The study was jointly led by Murdoch Children’s Research Institute (MCRI) and the University of Melbourne and published as:
Nguyen, N. N. L., et al. (2025). Plasma proteome adaptations during feminizing gender-affirming hormone therapy. Nature Medicine. doi.org/10.1038/s41591-025-04023-9
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