Ovarian Failure, Premature
Conditions
Brief summary
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
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.
Interventions
DRUG17beta Estradiol
Oral pill given daily at increasing doses every 6 months for 18 months.
Oral pill, started at a low dose taken daily, dose increased every 6 months for 18 months
DRUG17Beta Estradiol - transdermal
Transdermal estrogen patch, started at low dose with increasing doses eery 6 months for 18 months
DRUGProgesterone, micronized
Given starting at 18 months
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
12 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estradiol | end of study (up to 2 years) | 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. |
Countries
United States
Participant flow
Recruitment details
from 2007-2011 study participants were recruited from pediatric endocrinology clinics at Lucile Packard Children's Hospital at Stanford.
Participants by arm
| Arm | Count |
|---|---|
| Transdermal 17Beta Estradiol 17Beta Estradiol - transdermal: Transdermal estrogen patch, started at low dose with increasing doses eery 6 months for 18 months
Progesterone, micronized: Given starting at 18 months | 5 |
| Oral Conjugated Equine Estrogen Conjugated estrogens: Oral pill, started at a low dose taken daily, dose increased every 6 months for 18 months
Progesterone, micronized: Given starting at 18 months | 8 |
| Oral 17beta Estradiol 17beta Estradiol: Oral pill given daily at increasing doses every 6 months for 18 months.
Progesterone, micronized: Given starting at 18 months | 7 |
| Total | 20 |
Baseline characteristics
| Characteristic | Transdermal 17Beta Estradiol | Oral Conjugated Equine Estrogen | Oral 17beta Estradiol | Total |
|---|---|---|---|---|
| Age, Continuous | 14.2 years STANDARD_DEVIATION 0.5 | 13.8 years STANDARD_DEVIATION 0.4 | 14.5 years STANDARD_DEVIATION 0.6 | 14.2 years STANDARD_DEVIATION 0.6 |
| Follicle Stimulating Hormone (FSH) | 76 mIU/mL | 86 mIU/mL | 71 mIU/mL | 78 mIU/mL |
| Luteinizing Hormone (LH) | 14 mIU/mL | 26 mIU/mL | 13 mIU/mL | 18 mIU/mL |
| Sex/Gender, Customized Female | 5 participants | 8 participants | 7 participants | 20 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 5 | 0 / 8 | 0 / 7 |
| serious Total, serious adverse events | 0 / 5 | 0 / 8 | 0 / 7 |
Outcome results
Primary
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.
Time frame: end of study (up to 2 years)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transdermal 17Beta Estradiol | Estradiol | 53 pg/mL | Standard Error 19 |
| Oral Conjugated Equine Estrogen | Estradiol | 14 pg/mL | Standard Error 5 |
| Oral 17beta Estradiol | Estradiol | 12 pg/mL | Standard Error 5 |