Clinical trial NCT05865262: Protocol TRANS and QT Repolarization
Official title: Analysis of Ventricular Repolarization by QT Measurement in Transgender People Treated With Hormone Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Transgender Individuals
QTc Interval
Keywords: Transgender
QTc
testoterone
estradiol
ventricular repolarization
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: APHP
First posted: 2023-05-18
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with gender dysphoria consulting as part of the usual standard of care follow-up in endocrinology for instauration or follow-up of GAHT

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).

Eligibility criteria: 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

Primary outcomes:
measure: To assess the impact of GAHT on QTc duration in transgender individuals before and after starting therapy
timeFrame: assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)
Secondary outcomes:
measure: To assess the difference in PR, QRS, RR, QTc duration between men and women prior to GAHT, and transmen and transwomen already on GAHT.
timeFrame: assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)
measure: To assess the impact of gender-affirming hormone treatment on PR, QRS, RR duration in transgender individuals before and after starting GAHT
timeFrame: assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)
measure: To assess the association between the hormonal and ionic levels with PR, QRS, RR, QTc duration in transgender individuals before and on GAHT.
timeFrame: assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)
Other outcomes:
Locations:
city: Pessac
country: France
facility: University Hospital Bordeaux, France
Study officials:
affiliation: Groupe Hospitalier Pitie-Salpetriere
name: Joe-Elie Salem, Pr
role: STUDY_CHAIR
References: