Pre-pubertal Low Dose Transdermal Estradiol in Turner Syndrome

August 24, 2026 updated by: Children's National Research Institute

Ultra-low Dose Transdermal Estradiol Therapy in Prepubertal Girls With Turner Syndrome and Primary Ovarian Insufficiency.

This is a research study to find out if treatment with transdermal estradiol patches started between 8 to 11.5 years is safe in girls with Turner syndrome who have ovarian failure and to see whether it may improve performance on two tests of working speed and short-term memory.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The investigators hypothesize that ultra-low dose TDE will improve neurocognitive measures without a negative impact on growth and pubertal maturation in the peripubertal period. To test this hypothesis, investigators will conduct a prospective single center pilot trial and recruit up to 15 girls with TS and POI (FSH>10 in the past year), ages 8 to <11.5 years who will receive ultra-low dose TDE [defined as 1/8th patch of 0.025mg/24h applied weekly (delivering 3.125mcg/24h)] for 6 months to address the following objectives.

Primary: Study the effect of ultra-low dose TDE therapy on processing speed and working memory. The investigators will administer the Pattern Comparison Processing Speed Test as well as the List Sorting Working Memory test NIH toolbox EnglishV3 at baseline, and 6-months of TDE treatment.

Secondary: Assess change in pubertal status, FSH, LH and estradiol levels with ultra-low dose TDE therapy. Height, weight measurements, assessment of Tanner staging for breast development, laboratory measurements of ultrasensitive estradiol, FSH, LH, lipid profile at baseline and 6-months of TDE treatment will be completed

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Children's National Hospital
        • Contact:
        • Principal Investigator:
          • Roopa Kanakatti Shankar, MBBS, MS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Provision of signed and dated informed consent form
  2. Stated willingness to comply with all study procedures and availability for the duration of the study
  3. Female, aged 8 years up to 11 y and 180 days with karyotype confirmed Turner syndrome
  4. FSH result> 10miu/mL in the past 12 months. Since variability in FSH is not uncommon, a single measure of FSH >10mIU/mL in the past calendar year will be deemed sufficient for inclusion into the study even if repeat measures may be under 10mIU/mL.
  5. Ability to take the transdermal estradiol medication and be willing to adhere to the treatment regimen
  6. Ability to complete the primary endpoint testing in English. Non-English speakers may be recruited if the participant is capable of performing the English version of the tests.

Exclusion Criteria:

  1. Spontaneous thelarche with breast Tanner stage 3 or more, spontaneous menarche or history of abnormal uterine bleeding.
  2. Previous estrogen exposure
  3. Cognitive impairment is severe enough to prevent assessment of the primary outcome measures.
  4. Untreated hypothyroidism or celiac disease: Individuals may be recruited if on treatment and stable medication dose in past 3 months.
  5. Subjects known to have Y-chromosome material unless they have undergone gonadectomy and have fully external female genitalia
  6. History of any type of malignancy
  7. History of a known clotting disorder/deep venous thrombosis
  8. Any clinically significant abnormality as determined by the principal investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Estradiol Treatment
Patients opt to receive 6 months of transdermal ultra low dose estradiol treatment
Drug: Estradiol transdermal patch 0.025mg/24 hours- 1/8th fractionated patch
Estradiol transdermal patch 0.025mg/24 hours- 1/8th fractionated patch will be applied and changed weekly for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pattern Comparison processing speed test
Time Frame: 6 months
Changes in the Pattern Comparison processing speed test (PC) at 6 months on the NIH toolbox EnglishV3 compared to baseline. Pattern Comparison processing speed test (PC) is a measure of the speed of information processing. Participants see a pair of simple pictures on the iPad screen and must quickly discern whether the pictures are the same or different. The total raw score is the number of items answered correctly during the 80 seconds of presentation time (Max 133 items). The raw score is converted to a age-adjusted normative scores. The Median Response Time Per Item is also available.
6 months
List Sorting Working Memory (LSWM) test
Time Frame: 6 months
Changes in the List sorting working memory test on the NIH toolbox EnglishV3 at 6 months compared to baseline. The List Sorting Working Memory test measures a participant's working memory, the ability to hold information in a short-term buffer and then manipulate the information. Pictures and written names of different foods and animals are displayed with accompanying audio-recorded and visual prompts, and the participant is asked to say the items back in size order from smallest to largest, first within a single dimension and then on two dimensions. The raw score (up to 24 Max) is then converted to age-adjusted normative scores.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Breast Tanner stage
Time Frame: 6 months
Changes in breast sexual maturity rating (Tanner staging) on examination over 6 months with ultra-low dose estradiol treatment
6 months
Pubertal hormone changes
Time Frame: 6 months
Changes in serum estradiol (measured in pg/mL), after 6 months of ultra-low dose estradiol treatment compared to baseline.
6 months
LH
Time Frame: 6 months
Luteinizing hormone (LH) (measured in U/L) over 6 months of estradiol therapy
6 months
FSH
Time Frame: 6 months
Change in Follicle stimulating hormone (FSH) measured in U/L over 6 months of estradiol therapy
6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Height velocity
Time Frame: 6 months
Change in annualized height velocity (in cm/year) over 6 months of treatment with ultra-low dose estradiol. This will be calculated based on height measurements (in cm) at baseline and 6 months.
6 months
Lipid profile
Time Frame: 6 months
Changes in lipid profile (total cholesterol, triglycerides, high density lipoproteins, low density lipoproteins) over 6 months of treatment with ultra-low dose estradiol will be assessed.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's National Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

August 5, 2026

First Submitted That Met QC Criteria

August 24, 2026

First Posted (Actual)

August 25, 2026

Study Record Updates

Last Update Posted (Actual)

August 25, 2026

Last Update Submitted That Met QC Criteria

August 24, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00002034

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Patient Privacy and on account of being a pilot trial

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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