Evaluation of the Effectiveness of Hormonal Treatment in Adolescents Suffering from Gender Dysphoria (TRANSADO)

Gender dysphoria (GD) is a significant suffering lasting more than 6 months in a subject, with regard to the discrepancy felt between his or her gender identity and his or her birth sex. From the onset of puberty, most of these self-identified transgender adolescents will persist in their transgender identity and will undergo hormonal and surgical reassignment when the time comes. International best practice guidelines recommend early treatment from the start of pubertal development to block pubertal progression, with the possibility of hormonal transition by administering sex hormones of the desired sex usually around the age of 16. However, in order to reduce the psychosocial consequences of GD, more and more referral teams are carrying out this transition from the age of 14, although no study has been published to show its benefit compared with a transition at the age of 16. In the absence of treatment, co-morbidity among adolescents suffering from gender dysphoria is very high, with anxiety-depressive states, suicidal risk and dropping out of school in the forefront. Our hypothesis is that hormonal transition started at an age closer to physiological puberty can significantly reduce this comorbidity and improve quality of life for these adolescents. This is the first therapeutic trial to be conducted in France in the transgender adolescent population, in an area where international recommendations based on the principles of Evidence Based Medicine are essentially derived from the clinical expertise of teams who have specialized in the care of transgender people for over forty years, while clinical data derived from structured research are still very scarce.

The results of this study will guide the care of transgender adolescents, allowing them, if the study is positive, to access hormonal treatments earlier and thus more quickly improve their overall functioning, anxiety-depressive symptoms and their quality of life.

Study Overview

• Status: Recruiting
• Conditions: Gender Dysphoria
• Intervention / Treatment: Drug: hormonal treatment with cross sex hormones (testosterone or oestrogenes) started at 14 years old +/- 6 months; Drug: Cross sex hormones ( œstrogenes or testosterone) started at 16 years old +/- 6 months

Detailed Description

Multicenter, controlled, randomized, open trial with blinded evaluation of the primary endpoint (Prospective Open Blinding Endpoint PROBE study). Randomization will be stratified by sex assigned at birth and the investigating center. The primary analysis will be intention-to-treat and multiple imputation methods will be used to handle missing data. After verification of the inclusion criteria by the child psychiatrist (selection visit), then the pediatric endocrinologist (inclusion visit), the adolescent will be included in the study and will benefit from an initial evaluation (T0) by a psychologist trained for the primary criterion (CGAS) and secondary psycho-affective criteria.The patients will then be sent again to the pediatric endocrinologist who will randomize the patient (via an IT platform) and give them the treatment corresponding to their assigned group. Adolescents in both groups will be reassessed at 16 years +/- 6 months (T1). At the end of this evaluation, patients in the control group will begin their hormonal treatment. Adolescents will undergo a final evaluation at 18 years +/- 6 months (T2), at which time the same criteria as at T0 and T1 will be collected.

Main objective: To evaluate, in gender dysphoric adolescents, having completed their social transition, having or not undergone prior pubertal suppression, the effectiveness of hormonal treatment with estrogens or testosterone initiated at 14 years +/- 6 months of age on the overall functioning of the teenager at 16 years +/- 6 months old.

Primary endpoint: Children's Global Assesment Scale (CGAS) score at age 16 +/- 6 months

Secondary objectives : Evaluate, in gender dysphoric adolescents who have completed their social transition, whether or not they have benefited from prior pubertal suppression:

• the effectiveness of hormonal treatment started at 14 years old +/- 6 months vs. 16 years old +/- 6 months on the overall functioning of the adolescent at 18 years old+/- 6 months,
• the safety (side effects) of hormonal treatment started at age 14 +/- 6 months,
• and the relevance of hormonal treatment started at 14 years old +/- 6 months on other parameters assessed at 16 +/- 6 months and 18 +/- 6 months years old (gender identity, depression, anxiety, emotional, behavioral disorders and other comorbidities, objective and subjective quality of life, body image, height, waist/hip ratio, bone mineral density, BMI).

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Anne BISSERY; Phone Number: +33 (0)142162432; Email: anne.bissery@aphp.fr
• Study Contact Backup: Name: David COHEN, MD,PhD; Phone Number: +33 01 42 16 23 51; Email: david.cohen@aphp.fr

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Service de psychiatrie de l'enfant et de l'adolescent, GH Pitié-Salpêtrière
    • Contact: David Cohen; Phone Number: +33 0142162351; Email: david.cohen@aphp.fr
    • Contact: Julie Brunelle; Email: julie.brunelle@aphp.fr
  • Paris, France, 75019
    • Recruiting
    • Service d'Endocrinologie et Diabétologie Pédiatrique, CHU Robert Debré
    • Contact: Laetitia Martinerie; Phone Number: +33 0140035303; Email: laetitia.martinerie@aphp.fr
  • Paris, France, 75019
    • Recruiting
    • Service de Psychiatrie de l'enfant et de l'adolescent, CHU Robert Debré
    • Contact: Alexandre Michel; Phone Number: +33 0187275105; Email: alexandre.michel@aphp.fr
  • Ile de France
    • Le Kremlin Bicêtre, Ile de France, France, 94270
      • Not yet recruiting
      • Service Endocrinologie et Diabète de l'enfant, CHU Le Kremlin Bicêtre
      • Contact: Marie-Agathe Trouvin; Phone Number: +33 0145217291; Email: marieagathe.trouvin@aphp.fr
      • Contact: Anne-Sophie Lambert; Email: anne-sophie.lambert@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adolescents aged 14+/- 6 months,
• Having initiated puberty: tanner score ≥2 for FtM; tanner score ≥2 (clinic and/or testosterone >0.3 ng/mL) for MtF
• Presenting the criteria for gender dysphoria according to the DSM5 assessed by at least two child psychiatric interviews at least six months apart where the diagnosis of gender dysphoria was clinically established and that of associated autism spectrum disorder refuted and/or associated cognitive impairment, confirmed by specific scales (Gender Identity / Gender Dysphoria Questionnaire for Adults and Adolescents (GIDYQ-AA) and Utrecht Gender Dysphoria Scale (UGDS))
• Whose indication for hormonal transition has been validated in a multidisciplinary consultation meeting after at least one consultation with the pediatric endocrinologist with clinical examination, blood pressure measurement, and information on hormonal treatments in the context of gender dysphoria.

Exclusion Criteria:

• Contraindication to hormonal treatment (see paragraph 1.5)
• Hormonal treatment needs to be adjusted (FtM patients treated with anti-coagulants or with thrombophilia).
• Patients with risk of aggravation of certain diseases under oestrogen treatment (MtF patients with uncontrolled diabetes with HBA1C > 8%, patients with cholelithiasis, biliary lithiasis, systemic lupus erythematosus, severe asthma, severe arterial hypertension, severe migraines, otosclerosis, epilepsy not controlled by treatment).
• Patients with cancer with a risk of hypercalcemia (and associated hypercalciuria), linked to bone metastases.
• Severe cardiac, hepatic or renal failure or ischemic heart disease, due to the risk of severe complications characterized by edema, with or without congestive heart failure.
• Uncontrolled high blood pressure.
• Patients with epilepsy and migraine.
• Patients with current or history of thromboembolic events.
• Severe untreated chronic depression
• Current anticoagulant treatment
• Severe autism Spectrum Disorder (clinical screening, confirmed in cases of doubt by the Social Responsiveness Scale (SRS) Raw-score > 76, carried out as part of usual care in cases of clinical evidence,
• Cognitive deficit (clinical screening, confirmed by an QI < 80 on the Weschler scale (WISC V), carried out as part of the usual treatment in the event of clinical evidence.
• Refusal to participate in the study on the part of the adolescent or one of the holders of parental authority (both holders and the adolescent must sign a written consent after receiving appropriate information).
• No social security cover
• Participation in other intervention research
• Pregnancy in progress
• Insufficient knowledge of French

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: early hormonal treatment; early hormonal treatment initiated at 14 years +/- 6 months, in addition to usual care	Drug: hormonal treatment with cross sex hormones (testosterone or oestrogenes) started at 14 years old +/- 6 months; 4 years of follow up (FU) with evaluation at T0 (14 years old +/- 6 months), T1 (16 years old +/-6 months) and T2 (18 years old+/- 6 months) with eather ANDROGEL® 16.2 mg/g, gel (testostérone) or ESTREVA® 0.1 %, gel ou 1.3 PROVAMES® 1 mg, cp (oestrogenes)
Active Comparator: usual treatment; Usual care between 14 and 16 years +/- 6 months : child psychiatric consultations, endocrinological consultations and consultations with a psychologist, family interviews, network work with local health partners and national education. Then hormonal treatment initiated at 16 years +/- 6 months, in addition to usual care.	Drug: Cross sex hormones ( œstrogenes or testosterone) started at 16 years old +/- 6 months; 2 years of hormonal treatment from 16 old +/- 6 months to 18 years old +/- 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global functionning using the Children's Global Assessment Scale (CGAS)	The Children's Global Assessment Scale (CGAS), adapted from the Global Assessment Scale for adults, is a rating of general functioning for children and young people until 16 years old. The clinician assesses a range of aspects of psychological and social functioning and gives the child or young person a single score between 1 and 100, based on their lowest level of functioning. The score puts them in one of ten categories that range from "needs constant supervision" (1-10) to "superior functioning" (91-100). The measure can be used by clinicians as well as researchers to complement other scales measuring more specific symptoms.	16 years old +/- 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Depression Inventory (BDI)	is a 21-question multiple-choice self-report inventory, one of the most widely used psychometric tests for measuring the severity of depression.Min = 0 Max = 39 Between 0 and 3 = no Dépression	T0 (14 years old +/-6 mois); T1 (16 years old+/-6 monhs); T2 ( 18 years old +/-6 months)
State and Anxiety Inventory for Children (STAI-C)	STAI-C includes 20-items that describe anxiety experiences a person might experience (e.g., item 6-"I worry too much"©). For each item, participants choose one of three options that indicate how often they experience the described situation - "hardly-ever", "sometimes" or "often"; these options are scored with 1, 2, and 3 points, respectively (total score range: 20-60). Higher scores indicate higher anxiety	T0 (14 years old +/-6 mois); T1 (16 years old+/-6 monhs); T2 ( 18 years old +/-6 months)
Drug use (DEP-ADO)	Drug use: assessed by specific questions via the DEP-ADO questionnaire (screening grid for problem substance use among adolescents). Dep-Ado is a 15 minutes questionnaire to evaluate alcohol and substance use adolescent population aged 12 to 17 years. No problem if total score <12; warning of >12 et <19; pathological use needing intervention if >20	T0 (14 years old +/-6 months); T1 (16 years old+/-6 months); T2 ( 18 years old +/-6 months)
WISC-V (weschler Test)	cognitive test with 4 subscales (verbal comprehension index, perceptual reasoning index, logical score, working memory index, processing speed index). IQ is calculated. If <80, it is an non inclusion criteria. Normal range between 80 and 120. when > 120 précocity	T0 (14 years old +/-6 months); T2 ( 18 years old +/-6 months)
UGDS (Utrecht Gender Dysphoria Scale ) and GIDYQ-AA (Gender Identity/ Gender Dysphoria Questionnaire for Adolescents and Adults scale )	The Utrecht Gender Dysphoria Scale (UGDS) is a validated, 12-item screening measure for both adults and adolescents used extensively in gender clinics to assess gender dysphoria. Minimal score= 12; max=60. two versions (AFAB, AMAB)	selection visit ; T1 (16 years old +/-6 months) ; T2 (18 years old +/-6 months)
Body Image Scale (BIS)	The 10-item BIS was developed to assess changes in body image assessed with a four-point scale from "not at all" to "very much." High scores indicate higher body image.(Min=30, Max=150 )	T0 (14 years old +/-6 months); T1 (16 years old+/-6 months); T2 ( 18 years old +/-6 months)
World Health Organization Quality Of Life - BREF (WHOQOL-BREF)	This 26-item instrument measures four fields, i.e. physical health, mental health, social relations and the environment. The analysis is based on the scores generated for each field (no overall score can be calculated). The user manual is comprehensive, which makes the instrument easy to use (WHO, 1996). While some studies call into question the construct validity (D'Abundo et al., 2011), the WHOQOL-BREF is generally recognized as a reliable, valid instrument to assess quality of life and is widely used in the literature for clinical and population-based surveys (Oliveira, Carvalho and Esteves, 2016; Skevington, Lotfy and O'Connell, 2004).	T0 (14 years old +/-6 months); T1 (16 years old+/-6 months); T2 ( 18 years old +/-6 months)
Satisfaction With Life Scale (SWLS)	The SWLS is a short 5-item instrument designed to measure global cognitive judgments of satisfaction with one's life. The scale usually requires only about one minute of a respondent's time.Min=5, Max=35. The higher score means a greater satisfaction with life	T0 (14 years old +/-6 months); T1 (16 years old+/-6 months); T2 ( 18 years old +/-6 months)
Height, bone mineral density, BMI, waist to hip ratio	MI is a measurement of a person's leanness or corpulence based on their height and weight, and is intended to quantify tissue mass	inclusion visit (14 years old +/-6 months); T1 (16 years old+/-6 months); T2 ( 18 years old +/-6 months)
Mini International Neuropsychiatric Interview (MINI)	To assess the 17 most common psychiatric disorders and suicidality in DSM-III-R, DSM-IV and DSM-5 and ICD-10. The MINI was designed as a brief structured diagnostic interview to meet the need for a short but accurate structured psychiatric interview for multicenter clinical trials and epidemiology studies and to be used as a first step in outcome tracking in nonresearch clinical settings.	selection visit ; T1 (16 years old+/-6 months); T2 ( 18 years old +/-6 months)
The emotional and sexual relationship	The emotional and sexual relationship assessed by specific questions	T0 (14 years old +/-6 months); T1 (16 years old+/-6 months); T2 ( 18 years old +/-6 months)
School drop-out / family breakdown	School drop-out / family breakdown assessed by specific questions	T0 (14 years old +/-6 months); T1 (16 years old+/-6 months); T2 ( 18 years old +/-6 months)
Global Assesment Scale (GAS)	assess the adolescent's overall functioning, heteroquestionnaire, score from 1 to 100, on file and after 30-minute interview	T2 : 18 years old +/-6 months
Potential side-effects		T0 (14 years old +/-6 months); T1 (16 years old+/-6 months); T2 ( 18 years old +/-6 months)
Child Behaviour Checklist (CBCL) scale	Emotional disorders and possible comorbidities assessed by the Child Behavior Checklist (CBCL) score, parent self-questionnaire, 15 minutes	T0 (14 years old +/-6 months); T1 (16 years old+/-6 months); T2 ( 18 years old +/-6 months)
Youth Self Report (YSR) scale	Emotional disorders and possible comorbidities: assessed by the Youth Self Report (YSR) self-questionnaire, 15 minutes	T0 (14 years old +/-6 months); T1 (16 years old+/-6 months); T2 ( 18 years old +/-6 months)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Director: David COHEN, MD, PhD, Assistance Publique - Hopitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2024
• Primary Completion (Estimated): June 24, 2029
• Study Completion (Estimated): June 24, 2031

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: mental health; adolescents; hormonal treatment; Gender Dysphoria
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Sexual Dysfunctions, Psychological; Depressive Disorder; Gender Dysphoria; Depressive Disorder, Major; Antineoplastic Agents; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anabolic Agents; Androgens; Methyltestosterone; Testosterone 17 beta-cypionate; Testosterone; Testosterone undecanoate; Testosterone enanthate; Hormones
• Other Study ID Numbers: P170923J; 2019-000300-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No