Plasma proteome adaptations during feminizing gender-affirming hormone therapy
Authors' conclusion
These results reveal that feminizing GAHT reshapes the plasma proteome in a hormone-dependent manner, with implications for reproductive capacity, immune regulation and long-term health outcomes.
Study context
- Population
- Transgender individuals receiving feminizing gender-affirming hormone therapy (GAHT)
- Participants
- 40 individuals
- Comparison
- Feminizing GAHT with estradiol plus cyproterone acetate vs estradiol plus spironolactone
- Outcome
- Plasma proteome changes
- Follow-up
- 6 months
Methodological detailsprospective, 6-month follow-up
- Prospective
- 6-month follow-up
Main finding
As reported in the abstract
Proteins changed by feminizing GAHT (of 5,279 measured)
Cyproterone
245
events
Spironolactone
91
events
- Proportion of changed proteins showing a decrease
- >95%
Further findings
Events
| Outcome | Cyproterone | Spironolactone |
|---|---|---|
| Top 100 sex-associated proteins (UK Biobank) altered | 36 | 22 |
Top 100 sex-associated proteins (UK Biobank) altered
- Proteome remodelled toward a cis-female profile
Overlap with MHT-altered proteins in cis women
- Cyproterone-affected proteins overlapping with MHT-altered proteins, same direction (exceptions incl. CXCL13 and NOS3)
- 43%
Other proteome findings
- Spermatogenesis-associated proteins markedly decreased with cyproterone, attributable to loss of testosterone
- Changes in body fat % and breast volume reflected in proteome, incl. increased leptin
- Profile skewed toward asthma and autoimmunity; with cyproterone, away from atherosclerosis-associated profile
Original publication
Plasma proteome adaptations during feminizing gender-affirming hormone therapy. Nat Med. Published 20 October 2025. doi:10.
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