Long Term Effects of Oral Versus Transdermal Estrogen Replacement Therapy in Turner Syndrome
NCT Number: NCT06570460
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Turner Syndrome|Hypogonadism; Ovarian|Hormone Replacement Therapy|Estrogen Replacement Therapy|Estrogen Deficiency
Interventions: DRUG: 17-beta estradiol|DRUG: 17-beta estradiol
Sponsor: Aarhus University Hospital
Collaborators: University of Aarhus
Sex: FEMALE
Age: ADULT
Enrollment: 50
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2021-11-29
Completion Date: 2026-12-31
Locations: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Aarhus N, 8200, Denmark

Summary:
This 14-month, phase IV, randomized controlled crossover trial aims to compare the effects of oral versus transdermal estrogen replacement therapy (ERT) in women with Turner syndrome (TS). The study's objectives are to clarify endocrine, metabolic, cardiovascular, and thromboembolic risk factors in TS after a wash-out period without estrogen (E2) treatment; compare the effects of oral versus transdermal (TD) ERT regimens; and examine the long-term effects of E2 administration via these two routes. The study involves 50 TS women aged 18-50 years and 50 control participants. TS participants are randomized to receive either oral or TD ERT for six months, followed by crossover to the alternate treatment for another six months. Prior to randomization, any existing ERT will be discontinued for a 1-month washout period. A second 1-month washout period will occur between the two 6-month treatment phases. Laboratory analyses and clinical investigations are performed after the first wash-out period, after the first six months of treatment, and after the last six months of treatment. We anticipate that this study may provide a basis for new and improved recommendations for sex hormone replacement therapy in TS.

Primary Outcome Measures: Blood test values, Changes in blood test values of follicle stimulating hormone and luthenizing hormone from baseline, After 1 month of wash-out, 6 months of oral and six months of transdermal treatment|Blood test values, Changes in blood test values of estradiol from baseline, After 1 month of wash-out, 6 months of oral and six months of transdermal treatment|Dual energy X-ray absorptiometry, Changes in body composition and bone mineral density, After 6 months of oral and six months of transdermal treatment|Cardiovascular status, Changes in 24-hour blood pressure measurements, After 6 months of oral and six months of transdermal treatment|Cardiovascular status, Changes in arterial stiffness measured by SphygmoCor, After 6 months of oral and six months of transdermal treatment|Muscle quality (quadriceps femoris), MR scan of both quadriceps measuring muscle cross-sectional area (CSA) and fat content of the muscle. Maximal isometric muscle strength of both quadriceps (functional muscle tests). Muscle quality = maximum quadriceps strength measured in nM/muscle CSA., After 6 months of oral and six months of transdermal treatment|Functional muscle tests, Changes in maximal jumping height, After 6 months of oral and six months of transdermal treatment|Isometric muscle tests, Changes in maximal isometric hand strength, After 6 months of oral and six months of transdermal treatment|Maximal oxygen uptake test (VO2 max), Changes in maximal oxygen uptake, After 6 months of oral and six months of transdermal treatment
Secondary Outcome Measures: Self-reported health-related quality of life and functioning (SF-36), The Short Form 36 Health Survey is a self-reported quality of life questionnaire consisting of eight scaled scores. Each scale is transformed directly into a 0-100 scale, where a lower score indicates greater difficulty., After 6 months of oral and six months of transdermal treatment|Self-reported quality of life (WHOQoL-Bref), The WHOQoL-Bref is a questionnaire where the participant's answers to 26 questions are used to create an overall quality of life profile. This profile includes scores for each dimension of the questionnaire: physical health, mental health, social relationships, and the participant's environment., After 6 months of oral and six months of transdermal treatment|Subjective medication assesment, Subjective assesment of the medication after 6 months of use, After 6 months of oral and six months of transdermal treatment