A Study Comparing Different Treatment Approaches for the Initiation of Puberty in Girls With Turner Syndrome Using a TRIFECTA-DARED Approach for Rare Diseases

Turner syndrome is a condition in which a girl's body does not make enough estrogen on its own, so doctors give estrogen to help start breast and uterine (womb) development. Hence, the goal of this clinical trial is to learn whether two different ways of giving estrogen help girls and young women with Turner syndrome go through puberty normally, and to compare how well each method works and how safe they are. The main questions the trial aims to answer are: 1. Does taking an oral estrogen tablet (Progynova) or applying an estrogen gel (Oestrogel) lead to better breast development? 2. Does one method lead to a larger uterine size as seen on ultrasound? 3. Do participants start menstrual-like (withdrawal) bleeding, and does one method cause it sooner? 4. What side effects (for example, headaches, nausea, changes in blood tests) happen with each method? Who can take part? * Girls and young women aged 11-30 years with a confirmed diagnosis of Turner syndrome and no previous estrogen treatment. * They have not yet begun puberty (no breast growth, and a small uterus on ultrasound). * They agree to adhere to the study schedule and keep a diary of any bleeding or side effects What will happen to the participants during the clinical trial? * Get assigned at random to one of two groups (1:1 ratio): 1. Gel group: Apply Oestrogel (17β-estradiol) to the skin, starting twice a week, then daily with increasing doses over 19 months. 2. Tablet group: Swallow Progynova (estradiol valerate) tablets, starting twice a week, then daily with increasing doses over 19 months. * Visit the clinic at the start of study (baseline), month 1, 7, 13, and 19 for: 1. A physical exam (including breast staging). 2. An ultrasound to measure uterine length and thickness. 3. A blood test for safety checks (triglycerides and other markers). 4. Keep a diary noting any spotting or bleeding (called withdrawal bleeding) and any side effects. Why does this matter? Girls and young women with Turner syndrome often need estrogen to begin puberty safely. This trial will show which method-gel or tablets-best mimics natural puberty (breast and uterine growth), how quickly menstrual-like bleeding begins, and which has fewer unwanted effects. The findings will help doctors choose the most effective and safe treatment for people with Turner syndrome.