Cardiomodulatory Effects of Gender-Affirming Hormone Therapy

The aim of this study is using a prospective and cross-sectional observational design, to assess the effect of initiation and effect of gender-affirming hormone therapy in trans men (female to male) and in trans women (male to female) on:

* Cardiovascular risk factors, including blood pressure, body mass index, body composition, and blood lipids
* Cardiovascular function, structure and anatomy as assessed by cardiovascular magnetic resonance (CMR) imaging and transthoracic echocardiography
* Circulating cardiovascular and inflammatory biomarkers assessed by immunoassays and proteomic profiling
* Self-reported health-related quality of life.

The study will have one longitudinal group where 60 trans women and 60 trans men are followed from the start of treatment till 6-12 months after. An age-matched control group will go through the same assessments.

The second part of the study will be cross-sectional, where the investigators aim to include 100 trans women and 100 trans men already on gender-affirming hormone therapy and being followed at Oslo University Hospital by an endocrinologist.

In both these group, patients who both previously or currently are using Gonadotropin-releasing hormone agonists (GnRH-agonists), so called puberty blockers, will also be eligible for inclusion.

Primary outcomes

• Change in left ventricular mass (g) [6-12 months]: Assessed by cardiac magnetic resonance (CMR) from baseline to end of study.

Secondary outcomes

• Change in left ventricular end-systolic volume (LVES) and end-diastolic volume (EDV) (mL) [6-12 months]: Assessed by cardiac magnetic resonance (CMR) and echocardiography from baseline to end of study.
• Change in left ventricle ejection fraction (LVEF) (%) [6-12 months]: Assessed by cardiac magnetic resonance (CMR) and echocardiography from baseline to end of study.
• Change in concentration of circulating cardiac biomarkers [6-12 months]: Cardiac biomarkers defined as cardiac troponins I and T measured by high sensitivity assays (hs-TnI and hs-TnT) (ng/L) and N-terminal proB-type natriuretic peptide (NT-proBNP) (ng/L), compared from baseline to end of study.
• Change in concentration in markers of blood lipids [6-12 months]: Blood samples will be collected and assessed from baseline to end of study. Blood samples will include markers such as cholesterol, LDL, and HDL (mmol/L).
• Change in concentration in markers of cardiometabolic risk factors such as insulin resistance [6-12 months]: Blood samples will be collected and assessed from baseline to end of study. Blood samples will include the marker HbA1c (mmol/mol).
• Changes in global longitudinal strain (GLS) (%) and global circumferential strain (GCS) (%) [6-12 months]: Assessed by cardiac magnetic resonance (CMR) and echocardiography from baseline to end of study.
• Change in arterial stiffness assessed as the pulse wave velocity (m/s) [6-12 months]: Assessed by cardiac magnetic resonance (CMR) and echocardiography from baseline to end of study.
• Change in arterial stiffness assessed as the aortic distensibility (mmHg-1) [6-12 months]: Assessed by cardiac magnetic resonance (CMR) and echocardiography from baseline to end of study.
• Change in blood pressure (mmHg) [6-12 months]: Blood pressure, both systolic and diastolic blood pressure, will be measured in a standardized manner.
• Change in body mass index (BMI) [6-12 months.]: Weight and height will be measured in a standarized manner and calculated into BMI (kg/m2).
• Change in body composition [6-12 months.]: Body composition will be evaluated using dual-energy x-ray absorptiometry (DXA).
• Change in self-reported health-related quality of life (SF-36) [6-12 months]: For participants aged 18 years or older, the questionnaires SF-36 will be used. SF-36 gives eight scaled scores, each ranging from 0 to 100. Higher scores indicates better health-related quality of life.
• Change in self-reported health-related quality of life (PedsQL) [6-12 months]: For patients aged 16-18, the questionnaire PedsQL will be used. Each question is scored 0-4 and each item response is linearly transformed to a 0-100 scale where higher scores indicate better health-related quality of life.
• Change in self-reported health-related quality of life (GHQ-12) [6-12 months]: For participants aged 18 years or older, the questionnaires GHQ-12 will be used. The scale goes from 0 to 36 (Likert Method) with higher values indicating greater psychological stress.
• Change in self-reported health-related quality of life (SDQ) [6-12 months]: For participants aged 16-18 years of age, the questionnaire SDQ will be used. The scale goes from 0 to 50 with higher values indicating increasing symptoms of difficulties.
• Change in self-reported health-related quality of life (Chalders Fatigue Questionnaire) [6-12 months]: For all participants, the questionnaire Chalders Fatigue Questionnaire will be used. The scale goes from 0 to 33 with higher values indicating increasing symptoms of fatigue.

Sex: All, ages: 16 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Diagnosis of gender-incongruence
* Scheduled to initiate gender-affirming hormone therapy at Oslo University Hospital or currently being followed by an endocrinologist for gender-affirming hormone therapy at Oslo University Hospital
* Being 16 years or older

Exclusion Criteria:

\- History of clinically significant cardiovascular disease

For the healthy controls, these exclusion criteria also apply:

* No daily smokers
* No endocrine disorders
* No daily medications (except contraception and seasonal medication such as antihistamines)

• Torbjørn Omland, MD, PhD, MPH, Principal investigator, University of Oslo