Defining the Optimal Hormonal Replacement Therapy in Turner Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to examine whether a larger dosage of estrogen than the one used today will secure the development of a normal sized uterus and increase the strength of the bones in girls and young women with Turner syndrome. The purpose is also to evaluate whether aortic dilatation is present in this group of patients, and if the estrogen dosage will influence the emotional well-being and self-esteem of the patients.

Detailed Description
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Turner syndrome is a common chromosomal disorder with only one X-chromosome or partial deletions in one X-chromosome in all or some of the cell-lines in the body. Appr. 18 girls/year are being born with the syndrome in Denmark. The syndrome is mostly known for reduced final height and the lack of pubertal development with infertility, but it is also known for diseases influencing other parts of the body like the heart with the risk of development of aortic dilatation and subsequently dissection with the risk of rupture, profuse bleeding and sudden death. Reduced bone strength and increased risk of bone fracture are also features of the syndrome. Treatment with growth hormone and female sex-hormones are well-established treatments. Girls and young women with Turner syndrome ages 10 to 21 years will participate. The girls ages 15 to 21 years will randomly and double blindly receive treatment with either 2 mg or 4 mg estrogen for 5 years. Yearly examinations with blood tests, physical examinations, questionnaires, ultrasound and MR-scan of the internal female genitalia, DEXA-scan of the bones and MR-scan of the heart will be performed.

Official Title
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The Growth of Genitalia Interna and the Bone Mineralization Under Hormonal Replacement Therapy and the Presence of Aortic Root Dilatation in Girls With Turner Syndrome

Conditions
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Turner Syndrome

Intervention / Treatment
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* Drug: estradiol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Verified Turner syndrome Ages 10-25 years Exclusion Criteria: Contraindications to the MR-scan Contraindications to the trial medication Severe or chronic sickness with impact on the parameters of the study or incompatibility with the trial medication Intake of medications with interactions with trial medication

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 4 mg estradiol<br> | Drug: estradiol<br>* tablets, 2 mg day 1 through day 22 of the menstrual cycle for 5 years<br>|
| Placebo Comparator: 2 mg estradiol<br> | Drug: estradiol<br>* tablets, 2 mg day 1 through day 22 of the menstrual cycle for 5 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The size of the uterus evaluated by magnetic resonance (MR)-scan |  | 5 years | 
| Bones evaluated by dual-energy X-ray absorptiometry (DEXA)-scan |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The diameter of the aortic root evaluated by MR-scan |  | 5 years | 
| Development of biochemical markers |  | 5 years | 
| Body composition evaluated by DEXA-scan |  | 5 years | 
| Emotional wellbeing and self-esteem evaluated by questionnaires |  | 5 years | 
| The size of the uterus evaluated by ultrasound |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Turner Syndrome, Hormonal replacement therapy, Bone mineralization, Uterine size, aortic root dilatation