Protocol TRANS and QT Repolarization (QTrans)

Analysis of Ventricular Repolarization by QT Measurement in Transgender People Treated With Hormone Therapy

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).

Study Overview

• Status: Completed
• Conditions: QTc Interval; Transgender Individuals
• Intervention / Treatment: Diagnostic test: ECG; Diagnostic test: blood test (assessing ionic and hormonal circulating levels)

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).

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• France
  • Pessac, France, 336004
    • University Hospital Bordeaux, France

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• 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

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

treated transgender people; 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.

Diagnostic test: ECG; A triplicate ECG and a blood test will be done during a medical consultation as part of the usual endocrinology follow-up. Included individuals seen prior to initiation of GAHT, will be assessed a second time (at least one month after GAHT start) with a triplicate ECG and a blood test similar to inclusion visit. Included individuals already on GAHT will be seen only once at the inclusion visit. Triplicates of 10seconds 12-lead digitized electrocardiogram will be recorded after few minutes of rest in the supine position. Electrocardiograms will be acquired with Mindray ECG BeneHeart R12. For each subject, RR, PR, QRS and QT interval durations will be assessed with a semiautomatic approach using the median representative beats (overlap method) generated from 10seconds ECG with a good quality (CalECG v3.7; AMPS, LLC). The QT interval will be measured and corrected for heart rate by Fridericia's formula.; Diagnostic test: blood test (assessing ionic and hormonal circulating levels); Blood samples for the determination of serum concentrations of estradiol, progesterone, testosterone, FSH, and LH will be collected on the same day as the ECG, in a dry tube and further assayed in the immunology laboratory of Bordeaux University Hospital (France). Estradiol, progesterone, FSH, and LH plasma concentrations will be assayed by immunochemiluminescence (Architect i2000SR; Roche Diagnostics), and testosterone levels by liquid chromatography mass spectrometry. Kalemia and calcemia will be collected in a BD Vacutainer tube with heparin lithium and separator, further assayed at the biochemistry laboratory of Bordeaux University Hospital by indirect potentiometric measurement (Architect c16000) and Arsenazo III SRM 956 colorimetrie (Architect c16000).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the impact of GAHT on QTc duration in transgender individuals before and after starting therapy	Difference in QTc duration before and after initiation of GAHT	assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the difference in PR, QRS, RR, QTc duration between men and women prior to GAHT, and transmen and transwomen already on GAHT.	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	assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)
To assess the impact of gender-affirming hormone treatment on PR, QRS, RR duration in transgender individuals before and after starting GAHT	Difference in PR, QRS, RR duration before and after initiation of GAHT.	assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)
To assess the association between the hormonal and ionic levels with PR, QRS, RR, QTc duration in transgender individuals before and on GAHT.	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	assessments at inclusion and during follow-up visit in endocrinology department (minimum 1 month and max 2 years after treatment started)

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: APHP
• Investigators: Study Chair: Joe-Elie Salem, Pr, Groupe Hospitalier Pitie-Salpetriere

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2021
• Primary Completion (Actual): November 16, 2021
• Study Completion (Actual): January 1, 2023

Study Registration Dates

• First Submitted: April 26, 2023
• First Submitted That Met QC Criteria: May 9, 2023
• First Posted (Actual): May 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: estradiol; QTc; Transgender; ventricular repolarization; testoterone
• Other Study ID Numbers: 2021.11.16_Grouthier

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No