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

Launched by UNIVERSITI KEBANGSAAN MALAYSIA MEDICAL CENTRE · Jun 19, 2025

Keywords

ClinConnect Summary

This clinical trial is studying two different ways of giving estrogen medicine to girls and young women with Turner syndrome, a condition where the body doesn’t produce enough estrogen naturally. Estrogen is important because it helps start puberty, including breast growth and the development of the uterus (womb). The study wants to find out whether taking estrogen as a tablet (called Progynova) or applying it as a skin gel (called Oestrogel) works better and is safer. Researchers will look at breast development, how the uterus grows, when menstrual-like bleeding starts, and any side effects like headaches or nausea.

Girls and young women aged 11 to 30 with Turner syndrome who have not yet started puberty and have never taken estrogen treatment before may be eligible to join. Participants will be randomly assigned to either the tablet or gel group. Over 18 months, they will gradually increase their estrogen dose and visit the clinic every 6 months for check-ups, including physical exams, ultrasound scans, and blood tests. They will also keep a diary to record any bleeding or side effects. This study will help doctors understand which treatment method best supports safe and natural puberty for people with Turner syndrome.

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • 1. Females aged 11-30 years old with karyotype-verified (45, X or other similar karyotypes) and clinically confirmed Turner's syndrome prior at the time of pubertal induction
• • 2. Confirmed estrogen deficiency with primary ovarian failure (high level of follicular stimulating hormone (FSH \> 25 IU/L))
• • 3. Patients who have not undergone pubertal development ( no breast development and underdeveloped uterus size).
• • 4. Hormone Replacement Therapy (HRT)-naive TS patients
• • 5. Breast Tanner Stage of 2 or less.
• • 6. Patients on Growth Hormone (GH) will be allowed entry into the study.
• • 7. Consented to trial participation (from individual TS patients (if aged 18 and above) or the parents or guardians (for under-18 TS patients) with individual's assent
• Exclusion Criteria:
• • 1. Patients with signs of spontaneous puberty
• • 2. Contraindications to trial products (e.g hypersensitivity to any components of the HRT) based on the most recent version of the British National Formulary (BNF 85)
• • 3. Previous history of exposure to estrogen treatment.
• • 4. Concomitant use of other drugs that affect the bone mineral density (BMD) of the participants (e.g. Bisphosphonates or prolonged use of systemic corticosteroids). Vitamin D supplementation and short corticosteroid usage are allowed.
• • 5. Acute or chronic hepatic disease
• • 6. Patients with untreated hypothyroidism
• • 7. Inflammatory bowel disease (Ulcerative Colitis, Crohn's disease) and coeliac disease
• • 8. Cigarette smoking patients
• • 9. Severely obese patients (BMI \> 95th percentile)
• • 10. Unknown abnormal genital bleeding
• • 11. Porphyria
• • 12. Recent involvement with clinical research studies (previous 6 months) investigating new HRT formulations