Comparison of Transdermal and Oral Estrogens in Adolescent Girls With Ovarian Failure

Study Overview
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Brief Summary
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To directly compare the safety (by laboratory evaluation) and efficacy (feminization and growth) of three commonly used estrogen preparations in adolescent patients with ovarian failure, either due to congenital causes (Turner syndrome) or medical therapies. We hypothesize that transdermal estrogen will have equivalent efficacy and a more favorable safety profile in comparison with conventional oral estrogen replacement.

Detailed Description
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Treatment with transdermal 17beta(17β) estradiol resulted in higher estradiol levels and more effective feminization compared to oral conjugated equine estrogen but did not result in an otherwise different biochemical profile in this limited number of heterogeneous patients. OBE (oral beta estradiol) and TBE (transdermal beta estradiol) provide safe and effective alternatives to OCEE (oral conjugated equine estrogen) to induce puberty in girls, but larger prospective randomized trials are required.

Official Title
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Comparison of Transdermal and Oral Estrogens in Adolescents With Ovarian Failure

Conditions
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Ovarian Failure, Premature

Intervention / Treatment
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* Drug: 17beta Estradiol
* Drug: Conjugated estrogens
* Drug: 17Beta Estradiol - transdermal
* Drug: Progesterone, micronized


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: in whom initiation of estrogen therapy has been recommended due to ovarian failure Outpatients age >=12 years to 17.99 years old Exclusion Criteria: spontaneous menses significant concurrent medical problem including: Liver function tests (LFTs) 3 times normal clotting disorder ongoing cancer treatment

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vivelle-Dot<br>17Beta Estradiol - transdermal | Drug: 17Beta Estradiol - transdermal<br>* Transdermal estrogen patch, started at low dose with increasing doses eery 6 months for 18 months<br>* Other names: Vivelle-Dot;Drug: Progesterone, micronized<br>* Given starting at 18 months<br>* Other names: Prometrium;|
| Active Comparator: Premarin<br>Conjugated estrogens | Drug: Conjugated estrogens<br>* Oral pill, started at a low dose taken daily, dose increased every 6 months for 18 months<br>* Other names: Premarin;Drug: Progesterone, micronized<br>* Given starting at 18 months<br>* Other names: Prometrium;|
| Active Comparator: Estrace<br>17beta Estradiol | Drug: 17beta Estradiol<br>* Oral pill given daily at increasing doses every 6 months for 18 months.<br>* Other names: Estrace;Drug: Progesterone, micronized<br>* Given starting at 18 months<br>* Other names: Prometrium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estradiol | Estradiol blood levels at end of study compared across groups to determine effect of dosing methods. Significance of levels depends on the stage of puberty and goals of therapy. | end of study (up to 2 years) |