Pre-pubertal Low Dose Transdermal Estradiol in Turner Syndrome

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.

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

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.