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Protocol TRANS and QT Repolarization

Completed
Conditions
Transgender Individuals
QTc Interval
Interventions
Diagnostic Test: ECG
Diagnostic Test: blood test (assessing ionic and hormonal circulating levels)
Registration Number
NCT05865262
Lead Sponsor
University Hospital, Bordeaux
Brief Summary

The consequence of hormone-based treatment on cardiac electrophysiology in transgender individuals is poorly explored. We will investigate the effects of gender affirming hormone treatments on ventricular repolarization (ie. QTc, QT corrected for heart rate duration) in a prospective cohort of transgender individuals before and after feminizing and masculinizing treatments, and transversally in transgender individuals on gender affirming hormone treatments. This monocentric cohort will be included in the Endocrinology department of the Haut-Leveque Hospital in Pessac (France).

Detailed Description

An essential step in the care of gender dysphoria is gender-affirming hormone therapy (GAHT) combining an anti-androgen and estrogen therapy in transgender women (formerly male to female) or androgen therapy in transgender men (female to male). Several studies have shown a detrimental effect of GAHT on cardiovascular risk factors and therefore, the European Society of Endocrinology recommend an enhanced monitoring of cardiovascular risk factors in transgender population. Data on the risk of cardiac arrhythmias in transgender population are lacking, particularly on ventricular repolarization and QTc.

Indeed, sex steroid hormones and gonadotropins are known to alter the cardiac electrophysiology, as shown in various animal and human studies. From puberty to menopause, the QTc is generally longer in women than in men, translating into a higher risk of Torsade de Pointes (a peculiar form of ventricular arrhythmia) in women versus men. Recent publications have well illustrated the shortening of QTc in women in situation of biological hyperandrogenism and; QTc lengthening in hypogonadal men which was reversed by restoration of physiological eugonadal testosterone levels. Gonadotrophin's levels were positively correlated with QTc. To date, no study has focused on changes in cardiac repolarization in the transgender population and particularly on the effects of GAHT.

The aim of this study is to evaluate the impact of feminizing and masculinizing hormone treatments (GAHT) on ventricular repolarization (i.e QTc) in transgender individuals, followed at the Endocrinology department of the Haut-Leveque hospital in Pessac.

We aim to enroll consecutively (monocentric cohort) transgender individuals (on and before treatment) consulting to the endocrinology department for their usual standard of care follow-up until we include 15 transgender men and 15 transgender women with 2 QTc assessments available, one before and the other after initiation of GAHT (triplicates of 10 sec ECGs, Fridericia's heart rate correction for each time-point). This effective (n=15/group) have ≥85% power to detect a difference in QTcF≥10msec between the ECG before and after initiation of GAHT with a paired t-test (α: 0.05; standard deviation of QTc in each subgroup: 12msec; expected QTcF mean: 410msec and 400msec in women and men before GAHT, respectively, intra-individual correlation: 0.5).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
120
Inclusion Criteria
  • Individuals with gender dysphoria consulting as part of the usual standard of care follow-up in endocrinology for instauration of the follow-up of GAHT
Exclusion Criteria
  • <18 years old
  • patients under protective measures or deprived of liberty (under guardianship, curatorship, safeguard of justice, incarcerated)
  • history of congenital long QT syndrome

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
treated transgender peopleECGTransgender individuals consulting at the Endocrinology department of the Haut-Leveque hospital in Pessac (France), whether they are (one unique visit) or not (2 visits) already on GAHT (feminizing hormone treatment in transgender women and masculinizing treatment in transgender men, respectively). Men and women not already on GAHT will have two visits in total, one inclusion visit before GAHT start and one at least after one month of GAHT (and maximum within 2 years of start). Transgender individuals already on GAHT will have one unique inclusion visit without any planned follow-up visit.
treated transgender peopleblood test (assessing ionic and hormonal circulating levels)Transgender individuals consulting at the Endocrinology department of the Haut-Leveque hospital in Pessac (France), whether they are (one unique visit) or not (2 visits) already on GAHT (feminizing hormone treatment in transgender women and masculinizing treatment in transgender men, respectively). Men and women not already on GAHT will have two visits in total, one inclusion visit before GAHT start and one at least after one month of GAHT (and maximum within 2 years of start). Transgender individuals already on GAHT will have one unique inclusion visit without any planned follow-up visit.
Primary Outcome Measures
NameTimeMethod
To assess the impact of GAHT on QTc duration in transgender individuals before and after starting therapyassessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)

Difference in QTc duration before and after initiation of GAHT

Secondary Outcome Measures
NameTimeMethod
To assess the impact of gender-affirming hormone treatment on PR, QRS, RR duration in transgender individuals before and after starting GAHTassessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)

Difference in PR, QRS, RR duration before and after initiation of GAHT.

To assess the association between the hormonal and ionic levels with PR, QRS, RR, QTc duration in transgender individuals before and on GAHT.assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)

Correlation (univariate and multivariate, including mixed effects models) between PR, QRS, RR, QTc duration and hormonal (progesterone, testosterone, FSH, LH, estradiol) and ionic (potassium, calcium) circulating levels

To assess the difference in PR, QRS, RR, QTc duration between men and women prior to GAHT, and transmen and transwomen already on GAHT.assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)

Difference in PR, QRS, RR, QT, QTc duration on digital ECG at initial inclusion visit between men and women prior to GAHT, and transmen and transwomen already on GAHT

Trial Locations

Locations (1)

University Hospital Bordeaux, France

🇫🇷

Pessac, France

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