Short summary

Gender affirming hormone therapy (GAHT) is a cornerstone in transgender care. The present large prospective study focus on an overall characterisation of the capacity of coagulation and fibrinolysis in transgender women and men subjected to different formulations and applications of GAHT. This will contribute with comprehensive and important knowledge about the mechanisms linking GAHT to thrombotic risk

Rationale

Transgender individuals experience an incongruence between their gender identity and their sex assigned at birth. Recent studies report that approximately 1% of the European population express incongruent gender identity. Improving quality of life in transgender persons is the primary goal of gender-affirming clinical care. Access to gender affirming treatment is almost unrestricted and the number of healthcare contacts due to gender-identity-related diagnoses have increased substantially in Denmark with a more than 10-fold increase during the last decade and the increase seems to continue. Gender affirming hormone therapy (GAHT) is a cornerstone in transgender care. GAHT includes lifelong combined oestradiol and anti-androgen treatment of transgender women and testosterone treatment of transgender men. Accordingly, sex hormone levels change up to 20-fold during transition in transgender persons compared to pre-treatment levels. The dramatic change in sex hormones during gender transition may affect the risk of cardiovascular diseases (CVD). CVD can be caused by atherosclerosis and thrombosis, and a disturbed balance between blood coagulation (leading to clot formation) and fibrinolysis (causing clot dissolution) will affect fibrin clot formation. Thus, an increase in coagulation activators or fibrinolytic inhibitors is prothrombotic, whereas an increase in coagulation inhibitors or fibrinolytic activators is antithrombotic, and will contribute to the pathogenesis of arterial and venous thrombosis. Treatment with sex hormones disturbs the balance between coagulation and fibrinolysis, but most of the current knowledge is gathered in cisgender populations Only few and selected factors within blood coagulation and fibrinolysis have been measured in transgender persons treated with GAHT. The present large prospective study focus on an overall characterisation of the capacity of coagulation and fibrinolysis in transgender women and men subjected to different formulations and applications of GAHT. This will contribute with comprehensive and important knowledge about the mechanisms linking GAHT to thrombotic risk. The aim of the study is to investigate the effect of 12 months of GAHT on coagulation and fibrinolysis with respect to the different routes of oestradiol administration in transgender women and testosterone administration in transgender men. We hypothesize that oestradiol therapy induces a prothrombotic effect in transgender women, with a more pronounced effect of oral formulations compared to transdermal formulations, and that testosterone therapy induces an antithrombotic effect in transgender men regardless of the route of administration.

Description of the cohort

The project is part of a clinical cohort (European Network for the Investigation of Gender Incongruence (ENIGI). This prospective cohort study is established through collaboration between Unit for Thrombosis Research, Department of Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg and Center for Gender Identity, Odense University Hospital, and the ENIGI-centres in Amsterdam, The Netherlands and Ghent, Belgium. Venous blood samples and clinical data from 347 transgender women and 414 transgender men subjected to GAHT were collected before initiation of therapy and after 12 months of GAHT, and inclusion of study participants is completed. The study population is divided according to the application modalities (transgender women: oral oestradiol + CPA or transdermal oestradiol + CPA; transgender men: testosterone injections or transdermal testosterone application).

Data and biological material

Clinical data: Demographic characteristics and clinical measurements include age, weight, height, waist and hip circumference, and blood pressure measured at baseline and after 12 months of GAHT. Blood samples: Plasma samples will be analysed for thrombin generation and fibrin lysability.

Collaborating researchers and departments

Department of Clinical Biochemistry, Esbjerg Hospital, University Hospital of Southern Denmark, Esbjerg, Denmark.

• Else-Marie Bladbjerg

Department of Endocrinology, Odense University Hospital

• Dorte Glintborg
• Marianne Skovsager Andersen
• Louise Lehmann Christensen

Department of Endocrinology and Metabolism, Center of Expertise on Gender Dysphoria, Amsterdam UMC, the Netherlands

• Chantal Maria Wiepjes
• Martin den Heijer

Department of Endocrinology and Center for Sexology and Gender, Ghent University Hospital, Ghent, Belgium

• Guy T'Sjoen