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

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

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.

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.

Turner Syndrome, Hormonal replacement therapy, Bone mineralization, Uterine size, aortic root dilatation

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

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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.