Platelet activation and coagulation biomarker concentrations were found to be increased in trans women and an inflammatory biomarker was found to be increased in trans men following 12 months of gender-affirming, transdermal hormone therapy, according to findings from a study published in PLoS One. Hormone therapy-induced changes in hemostatic and inflammatory biomarkers may explain the increased cardiovascular risk reported among transgender persons.

Researchers conducted a prospective, observational study analyzing data from 48 trans women and 47 trans men treated with gender-affirming, transdermal hormone therapy at a gender clinic in Amsterdam between June 2012 and July 2019. The trans women applied estradiol patches (100 mcg/24 h twice weekly) and cyproterone acetate (50 mg/d), and the trans men applied a testosterone gel (50 mg/d). Clinicians adjusted hormone treatment dosage, if required, to reach adequate estradiol or testosterone concentrations.   

The researchers measured inflammatory, coagulation, and adipose tissue biomarkers at baseline, 3 months, and 12 months. Inflammatory biomarkers included high-sensitivity C-reactive protein (hs-CRP), cytokines (α-1-antitrypsin, tumor necrosis factor-alpha, interferon-γ, and several interleukins), and vascular adhesion molecule-1. Coagulation biomarkers included fibrinogen and plasminogen activator inhibitor-1, as well as platelet factor-4, β-thromboglobulin, and p-selectin. Adipose tissue markers included leptin and adiponectin. Additional measurements included estradiol and testosterone concentrations, body mass index (BMI), and blood pressure.


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In trans women, fibrinogen increased by 15% (95% CI, 1-32) after 3 months; platelet activation markers platelet factor-4 and β-thromboglobulin increased by 17% (95% CI, 4-32) and 13% (95% CI, 2-24), respectively, after 12 months.

In trans men, the inflammatory biomarker hs-CRP increased by 71% (95% CI, 19-145), but platelet activation and coagulation biomarkers remained unchanged after 12 months. Correspondingly, systemic and endothelial inflammatory biomarkers decreased in trans women.

In both trans women and trans men, adipose tissue markers (leptin and adiponectin) shifted toward normal reference values of the respective gender.

The short duration of the study and inclusion of young, healthy participants may have mitigated the effect aging has on cardiovascular disease risk. Another limitation of the study is that the researchers analyzed only transdermal hormone therapy and excluded oral medications that undergo first-pass hepatic metabolism, particularly oral estrogens that increase risk of thrombosis. In addition, the researchers were unable to differentiate between the effects of transdermal estradiol and cyproterone acetate among the trans women.

“Our results are hypothesis-generating, and not hypothesis-confirming,” the authors said.

They continued, “While especially relevant for the trans population, gaining insight into the mechanism by which sex hormones affect cardiovascular risk may help to understand sex differences in cardiovascular disease in the cis population as well.”

Reference

Schutte MH, Kleemann R, Nota NM, et al. The effect of transdermal gender-affirming hormone therapy on markers of inflammation and hemostasis. PLoS One. 2022;17(3):e0261312. doi:10.1371/journal.pone.0261312