Clinical trial NCT00134745: Defining the Optimal Hormonal Replacement Therapy in Turner Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Turner Syndrome
Keywords: Turner Syndrome
Hormonal replacement therapy
Bone mineralization
Uterine size
aortic root dilatation
Lead sponsor: Hillerod Hospital, Denmark
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
name: The County of Frederiksborg
name: The foundation of Kaptajnløjtnant Harald Jensen and Wife
name: The foundation of Mrs. Olga Bryde
name: The foundation of Mr. Ivan Nielsen
First posted: 2005-08-25
Enrollment: 43
Sex: FEMALE
Minimum age (years): 10
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The size of the uterus evaluated by magnetic resonance (MR)-scan
timeFrame: 5 years
measure: Bones evaluated by dual-energy X-ray absorptiometry (DEXA)-scan
timeFrame: 5 years
Secondary outcomes:
measure: The diameter of the aortic root evaluated by MR-scan
timeFrame: 5 years
measure: Development of biochemical markers
timeFrame: 5 years
measure: Body composition evaluated by DEXA-scan
timeFrame: 5 years
measure: Emotional wellbeing and self-esteem evaluated by questionnaires
timeFrame: 5 years
measure: The size of the uterus evaluated by ultrasound
timeFrame: 5 years
Other outcomes:
Locations:
city: Hillerod
country: Denmark
facility: Pediatric Unit, Hillerod Hospital
state: Frederiksborg County
Study officials:
affiliation: Pediatric Unit, Hillerod Hospital
name: Line Cleemann, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cleemann L, Holm K, Fallentin E, Moller N, Kristensen B, Skouby SO, Leth-Esbensen P, Jeppesen EM, Jensen AK, Gravholt CH. Effect of Dosage of 17ss-Estradiol on Uterine Growth in Turner Syndrome-A Randomized Controlled Clinical Pilot Trial. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgz061. doi: 10.1210/clinem/dgz061.
citation: Brun S, Cleemann L, Holm K, Salskov G, Erlandsen M, Berglund A, Andersen NH, Gravholt CH. Five-Year Randomized Study Demonstrates Blood Pressure Increases in Young Women With Turner Syndrome Regardless of Estradiol Dose. Hypertension. 2019 Jan;73(1):242-248. doi: 10.1161/HYPERTENSIONAHA.118.11742.