Defining the Optimal Hormonal Replacement Therapy in Turner Syndrome

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

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.

Study Overview

• Status: Completed
• Conditions: Turner Syndrome
• Intervention / Treatment: Drug: estradiol

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.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Frederiksborg County
    • Hillerod, Frederiksborg County, Denmark, 4300
      • Pediatric Unit, Hillerod Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 25 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 4 mg estradiol	Drug: estradiol; tablets, 2 mg day 1 through day 22 of the menstrual cycle for 5 years
PLACEBO_COMPARATOR: 2 mg estradiol	Drug: estradiol; tablets, 2 mg day 1 through day 22 of the menstrual cycle for 5 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Line Cleemann
• Collaborators: Novo Nordisk A/S; The County of Frederiksborg; The foundation of Kaptajnløjtnant Harald Jensen and Wife; The foundation of Mrs. Olga Bryde; The foundation of Mr. Ivan Nielsen
• Investigators: Principal Investigator: Line Cleemann, Doctor, Pediatric Unit, Hillerod Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (ACTUAL): March 1, 2013
• Study Completion (ACTUAL): March 1, 2013

Study Registration Dates

• First Submitted: August 24, 2005
• First Submitted That Met QC Criteria: August 24, 2005
• First Posted (ESTIMATE): August 25, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): June 14, 2013
• Last Update Submitted That Met QC Criteria: June 13, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Turner Syndrome; Hormonal replacement therapy; Bone mineralization; Uterine size; aortic root dilatation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Endocrine System Diseases; Disease; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Heart Defects, Congenital; Cardiovascular Abnormalities; Chromosome Disorders; Sex Chromosome Disorders; Sex Chromosome Disorders of Sex Development; Syndrome; Turner Syndrome; Gonadal Dysgenesis; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: 120895