Cardiometabolic Protein Profile Changes During Gender-Affirming Hormone Therapy: A Prospective Clinical Study.

OBJECTIVE

Cardiovascular disease (CVD) risk is elevated in transgender individuals during gender-affirming hormone therapy (GAHT) with expected different mechanisms between T- and E2-based GAHT. We investigated prospective changes in cardiometabolic proteins relating to complement, inflammation, and transport during GAHT.

DESIGN

Prospective clinical study with assessment at baseline and after 1 year of GAHT.

PATIENTS: The main study population comprised 55 GAHT-naïve individuals (34 TM, 21 TF). An additional 35 GAHT-ongoing individuals (26 TM, 9 TF) were included as a cross-sectional comparison group at baseline.

MEASUREMENTS: 19 cardiometabolic proteins relating to atherosclerotic and thrombotic processes were analysed using targeted proteomics. Body composition was assessed by dual-energy X-ray absorptiometry.

RESULTS

In GAHT-naïve TM individuals, the mean age at baseline was 27 years and median BMI was 26.5 (22.3-28.9) kg/m2. Following T-based GAHT, complement factor H and B, 3, 4b, and transport proteins (sex hormone-binding globulin, ceruloplasmin, corticosteroid-binding globulin, vitamin D-binding protein, vitronectin, and afamin) decreased, and transthyretin increased. In GAHT-naïve TF individuals, the mean age at baseline was 27 years and median BMI was 21.5 (20.3-23.6) kg/m2. Following E2-based GAHT, complement factor H and B, 3, 4b, 9, C-reactive protein, immunoglobulin heavy constant alpha 1 (IGHA1), and transport proteins increased. In cross-sectional analyses, complement factor H and B, 3, 4b, 9, C-reactive protein, IGHA1, and afamin were higher in GAHT-ongoing TF individuals at baseline compared to GAHT-naïve TF individuals at 1 year.

CONCLUSION

T- and E2-based GAHT were associated with opposite directional changes in cardiometabolic protein profiles.

TRIAL REGISTRATION: ClinicalTrials. gov (Identifier: NCT04254354, NCT05169762).