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| Name | Class |
|---|---|
| Patty Brisben Foundation For Women's Sexual Health | OTHER |
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This pilot study will observe the progression of newly diagnosed POI patients physical and psychology outcomes after initiating standard of care HRT treatment in comparison to healthy female control participants' physical and psychology health over 24 months.
Background: Primary ovarian insufficiency (POI) is an enigmatic condition that affects ~1/10,000 women by age 20. Sometimes referred to as "early menopause," POI is characterized by estrogen deficiency among other hormonal abnormalities that resemble the menopause. POI is a serious chronic condition with no cure. The clinical presentation or 'phenotype' in adolescents is not well understood. Health consequences may include delayed or arrested puberty, skeletal losses, and the threat to reproductive health. Both the metabolic and emotional sequelae are substantial, and one of the most concerning is compromised bone health. The optimal hormone replacement therapy (HRT) regimen for these young women is debated and practice varies among health providers. Importantly only sparse data exist to guide clinicians to make evidence-based decisions regarding the management of these patients. If initiated early, HRT may prevent estrogen-associated bone loss.
Impact: Better understanding of POI may lead to improved treatments for this underserved population and have significant implications for the treatment of estrogen deficiency in other populations of adolescents and young women, and for all women going though natural menopause later in life. Little is known about the effects of HRT on bone health, body composition, cognition, and health-related quality of life, especially among adolescents. Understanding how this therapy affects these multiple health outcomes will fill knowledge gaps regarding treatment for young patients with POI, with potential implications for adolescents and young women with estrogen deficiency in other clinical settings. We will define the clinical presentation (i.e., phenotype) of adolescent POI. The pilot data collected will be used in a future application to the National Institutes of Health, to fund a larger trial that builds on observations from this initial study. The information gained from this pediatric model may also provide insights on management of the natural menopause that occurs in all women later in life.
Methods: Ten adolescents with idiopathic POI (i.e., from unexplained causes) will be recruited through the Cincinnati Children's Hospital Medical Center (CCHMC) Teen Health Center, Endocrine or Pediatric/Adolescent Gynecology Clinics. Ten healthy controls will be recruited from the Teen Health Center. Participants with POI will receive transdermal estrogen replacement (beginning at 25 µg/patch applied weekly), with the dose increased at subsequent study visits that will occur at 3, 6, 12, 18, and 24 months. All data collection will take place at the CCHMC Schubert Research Clinic. The investigators will measure bone density of the central skeleton and body composition by dual-energy x-ray absorptiometry. To evaluate the peripheral skeleton, bone and muscle measures will be obtained by peripheral quantitative computed tomography. At each visit, the participants will have blood drawn to measure circulating hormone levels that are characteristically altered in adolescents with POI, along with safety assays. Cognitive functioning will be assessed using standardized tools. Participants will complete quality of life assessments, along with nutrition and physical activity surveys. Lastly, all participants will also complete a detailed medical history and health assessment.
Implications/Future Directions: Once the phenotype of adolescent POI is more clearly defined, a logical next question will be to determine whether negative health outcomes can be prevented or modified. Data from the proposed trial will guide the design of future prospective studies that evaluate the effects of traditional treatments (e.g., HRT), including a longer study to monitor HRT therapy, as well as more experimental treatments (e.g., skeletal agents) that may benefit young women with this rare condition. In addition, findings are expected to open avenues of research for adolescents and women with estrogen deficiency in other clinical settings.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control Participants | No Intervention | The control group will reflect a comparison group similar to the POI patient group. As bone density, body composition, and cognitive domains continue to mature throughout the teenage years, this comparison group will provide an important metric of normal growth and development. | |
| POI Participants | Experimental | This group will be participants who have been recently diagnosed with POI. In an open-label fashion, participants with POI will receive Transdermal Estrogen(beginning at a dose of 25 μg/patch applied weekly), with the dose increased at 3, 6 12, and 18 months (to 37.5, 50, 75, and 100 µg/patch). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transdermal Estrogen | Drug | In an open-label fashion, participants with POI will receive transdermal estradiol (beginning at a dose of 25 µg/patch applied weekly), with the dose increased at 3, 6 12, and 18 months (to 37.5, 50, 75, and 100 µg/patch). |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Dual Energy X-ray Absorptiometry (DXA) Measure of Bone Mineral Density (BMD) of the Lumbar Spine | Change in height adjusted areal BMD Z-score of the lumbar spine from baseline to 24 months within groups. BMI Z-score, calcium intake, vitamin D intake and physical activity were included in the analysis. As DXA BMD Z-scores already include race, age, and sex, these variables were not included in the analysis. Z-scores ranging between -2.0 and 2.0 are considered normal. A Z-score <-2.0 is considered low. This analysis considers change in Z-score, therefore a high value reflects a greater increase in BMD Z-score. | Change in bone mineral density and body composition from baseline to 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Dual Energy X-ray Absorptiometry (DXA) Measure of Bone Mineral Density (BMD) at the Whole Body Less Head, Total Hip, and Femoral Neck | To assess changes in bone mineral density DXA height adjusted BMD Z-scores of the whole body less head, total hip and femoral neck were measured. BMI, calcium intake, vitamin D intake and physical activity were included in the analysis. As DXA BMD Z-scores already include race, age, and sex, these variables were not included in the analysis. Z-scores ranging between -2.0 and 2.0 are considered normal. A Z-score <-2.0 is considered low. This analysis considers change in Z-score, therefore a high value reflects a greater increase in BMD Z-score. |
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Inclusion Criteria for POI patients
The participant must:
Exclusion Criteria for POI patients
The participant must not:
Inclusion Criteria for Healthy Adolescent Control Participants
The participant must:
Be similar in age and race group to the idiopathic POI group
Have a BMI within 20% of the BMI of the case-matched participant
If postmenarchal, will be regularly menstruating (cycles between 21-35 days)
a. if POI participant is <12.5yrs (mean age of menarche) will match with a pre- menarchal control participant
Be English-speaking
Exclusion Criteria for Healthy Adolescent Control Participants
The participant must not:
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| Name | Affiliation | Role |
|---|---|---|
| Catherine Gordon, MD,Msc | Boston Children's Hospital and Cincinnati Children's Hospital Medical Center | Principal Investigator |
| Halley Wasserman, MD, MSc | Children's Hospital Medical Center, Cincinnati | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cincinnati Children's Hospital | Cincinnati | Ohio | 45229 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26087426 | Background | Gordon CM, Kanaoka T, Nelson LM. Update on primary ovarian insufficiency in adolescents. Curr Opin Pediatr. 2015 Aug;27(4):511-9. doi: 10.1097/MOP.0000000000000236. | |
| 19196677 | Background | Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009 Feb 5;360(6):606-14. doi: 10.1056/NEJMcp0808697. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Control Participants | The control group will reflect a comparison group similar to the POI patient group. As bone density, body composition, and cognitive domains continue to mature throughout the teenage years, this comparison group will provide an important metric of normal growth and development. |
| FG001 | Primary Ovarian Insufficiency (POI) Participants | This group will be participants who have been recently diagnosed with Primary ovarian Insufficiency (POI). In an open-label fashion, participants with POI will receive Transdermal Estrogen (beginning at a dose of 25 μg/patch applied weekly), with the dose increased at 3, 6 12, and 18 months (to 37.5, 50, 75, and 100 µg/patch). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
For these analyses, we included all participants who enrolled in the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Control Participants | The control group will reflect a comparison group similar to the POI patient group. As bone density, body composition, and cognitive domains continue to mature throughout the teenage years, this comparison group will provide an important metric of normal growth and development. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Dual Energy X-ray Absorptiometry (DXA) Measure of Bone Mineral Density (BMD) of the Lumbar Spine | Change in height adjusted areal BMD Z-score of the lumbar spine from baseline to 24 months within groups. BMI Z-score, calcium intake, vitamin D intake and physical activity were included in the analysis. As DXA BMD Z-scores already include race, age, and sex, these variables were not included in the analysis. Z-scores ranging between -2.0 and 2.0 are considered normal. A Z-score <-2.0 is considered low. This analysis considers change in Z-score, therefore a high value reflects a greater increase in BMD Z-score. | One POI participant had prior oral contraceptive exposure, no matched control, and did not follow up for subsequent visits. For these reasons it was recommended that her data not be included in the analyses. | Posted | Least Squares Mean | Standard Deviation | Z-score | Change in bone mineral density and body composition from baseline to 24 months |
|
Adverse events were collected from enrollment to completion of the 24 month visit
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control Participants | The control group will reflect a comparison group similar to the POI patient group. As bone density, body composition, and cognitive domains continue to mature throughout the teenage years, this comparison group will provide an important metric of normal growth and development. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| DVT | Blood and lymphatic system disorders | CTCAE (Unspecified) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pain/irritation at patch site | Skin and subcutaneous tissue disorders | CTCAE (Unspecified) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Halley Wasserman | CIncinnati Children's Hospital Medical Center | 513-803-3815 | halley.wasserman@cchmc.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 2, 2020 | Jan 25, 2024 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 8, 2020 | Apr 12, 2021 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D016649 | Primary Ovarian Insufficiency |
| ID | Term |
|---|---|
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| C511292 | Ortho Evra |
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|
| baseline to 24 months |
| Change in Volumetric Bone Mineral Density (vBMD) at the Distal Radius as Measured by Peripheral Quantitative Computed Tomography (pQCT) | To assess the appendicular (peripheral) skeleton, pQCT (Stratec XCT 2000, Orthometrix, Inc., White Plains, NY) bone measures were obtained of the non-dominant radius at the 3% and 66% sites. Measurements were acquired with a voxel size of 0.4 mm, slice thickness of 2.3 mm, and scan speed of 25 mm/sec, and analyzed with manufacturer software version 6. | Change from baseline to 24 months |
| Anthropometrics | The mean BMI in kg/m^2 is presented for each study group at baseline and at the 24 months follow up visit to show that there was no significant difference between groups nor a significant change in BMI over the duration of the study. | Baseline and 24 months |
| Change in Lean Mass as Measured by DXA Body Composition | Lean mass was obtained from the whole body DXA scan. Change in baseline to 24 months was assessed. | Change in lean mass from baseline to 24 months |
| Change in Symptoms of Anxiety as Measured by Screen for Child Anxiety Related Disorders (SCARED) | A 41 item self-report tool to assess for anxiety where each question receives a score of either 0, 1 or 2. Range of scores is 0 to 82. A total score of ≥ 25 may indicate the presence of an Anxiety Disorder. A higher score indicates there are more endorsed symptoms of anxiety. | Change from SCARED score baseline to 24 months |
| Change in Symptoms of Depression as Measured by Child Depression Inventory-II (CDI-II) | A brief self-report test that helps assess cognitive, affective and behavioral signs of depression in children and adolescents 7 to 17 years old. Scales include Emotional and Functional Problems, along with subscales of Negative mood/Physical symptoms, Negative Self-Esteem, Interpersonal Problems, and Ineffectiveness. The total score is converted into a T-score (mean=50, standard deviation=10) where a result >64 is considered elevated. A higher score indicates there are more endorsed symptoms of depression. | Change from CDI-II score from baseline to 24 months |
| Change in Memory as Assessed by the Children and Adolescent Memory Profile (CHAMP) Total Memory Index Score | The ChAMP is a norm-referenced test of memory and learning that was designed for use with children, adolescents, and young adults ranging from 5 through 21 years. The ChAMP includes 4 Subtests of visual and verbal memory to generate a total memory index score as a measure of overall memory. The total memory index score ranges from 50-150 with a mean=100 and standard deviation=15. Higher scores indicating better memory. The data presented here is the change in the total memory index score from baseline visit to the 24 month follow up time. | Change from score from baseline to 24 months |
| Change in Quality of Life as Assessed by the Child Health Questionnaire-Child Self-Report Form (CHQ-CF87) | The CHQ-87 is an 87-item self-report survey is designed to measure the physical and psychosocial health of adolescents. The total score ranges from 0-100. Higher scores indicate better quality of life. This instrument is reliable and valid for evaluating aspects of health pertinent across age, gender, health condition, and socioeconomic status in adolescents. | Change from baseline to 24 months |
| Compliance With Transdermal Estrogen Patch | Participants with primary ovarian insufficiency (POI) were prescribed weekly transdermal estrogen (TDE2) patches and asked to log on a patch calendar when they changed the patch. Patch calendars were reviewed for compliance and weeks where at least one patch was applied were considered to be in compliance. Weeks in compliance generated the numerator whereas total weeks of participation in the study constituted the numerator. | Patch Calendars were collected at 6 months, 12 months, 18 months and 24 months. Data presented is through study completion. |
| Study Medications - Serum Estradiol | Mean serum estradiol levels as measured in participants with POI. | Baseline, 12 months, 24 months |
| 24945456 | Background | Committee opinion no. 605: primary ovarian insufficiency in adolescents and young women. Obstet Gynecol. 2014 Jul;124(1):193-197. doi: 10.1097/01.AOG.0000451757.51964.98. |
| 23926553 | Background | Sadeghi MR. New hopes for the treatment of primary ovarian insufficiency/premature ovarian failure. J Reprod Infertil. 2013 Jan;14(1):1-2. No abstract available. |
| 27816219 | Background | Gordon CM, Zemel BS, Wren TA, Leonard MB, Bachrach LK, Rauch F, Gilsanz V, Rosen CJ, Winer KK. The Determinants of Peak Bone Mass. J Pediatr. 2017 Jan;180:261-269. doi: 10.1016/j.jpeds.2016.09.056. Epub 2016 Nov 3. No abstract available. |
| 25203144 | Background | Bakhsh H, Dei M, Bucciantini S, Balzi D, Bruni V. Premature ovarian insufficiency in young girls: repercussions on uterine volume and bone mineral density. Gynecol Endocrinol. 2015 Jan;31(1):65-9. doi: 10.3109/09513590.2014.958987. Epub 2014 Sep 9. |
| 19401379 | Background | Popat VB, Calis KA, Vanderhoof VH, Cizza G, Reynolds JC, Sebring N, Troendle JF, Nelson LM. Bone mineral density in estrogen-deficient young women. J Clin Endocrinol Metab. 2009 Jul;94(7):2277-83. doi: 10.1210/jc.2008-1878. Epub 2009 Apr 28. |
| 21917867 | Result | Zemel BS, Kalkwarf HJ, Gilsanz V, Lappe JM, Oberfield S, Shepherd JA, Frederick MM, Huang X, Lu M, Mahboubi S, Hangartner T, Winer KK. Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study. J Clin Endocrinol Metab. 2011 Oct;96(10):3160-9. doi: 10.1210/jc.2011-1111. Epub 2011 Sep 14. |
| Primary Ovarian Insufficiency (POI) Participants |
This group will be participants who have been recently diagnosed with POI. In an open-label fashion, participants with POI will receive Transdermal Estrogen(beginning at a dose of 25 μg/patch applied weekly), with the dose increased at 3, 6 12, and 18 months (to 37.5, 50, 75, and 100 µg/patch). |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| Bone Mineral Density Whole Body less head | A bone mineral density (BMD) Z-score is an age, sex and race specific measurement. Normal BMD Z-scores range from -2.0 to 2.0 with 0.0 representing population mean. Higher Z-scores indicate stronger bone density. Z-scores <-2.0 are considered low bone density for age. Height adjustments are made to account for short stature leading to falsely lower BMD Z-scores. | Mean | Standard Deviation | Z-score |
|
| Bone Mineral Density Lumbar Spine | A bone mineral density (BMD) Z-score is an age, sex and race specific measurement. Normal BMD Z-scores range from -2.0 to 2.0 with 0.0 representing population mean. Higher Z-scores indicate stronger bone density. Z-scores <-2.0 are considered low bone density for age. Height adjustments are made to account for short stature leading to falsely lower BMD Z-scores. | Mean | Standard Deviation | Z-score |
|
| Bone Mineral Density Total Hip | A bone mineral density (BMD) Z-score is an age, sex and race specific measurement. Normal BMD Z-scores range from -2.0 to 2.0 with 0.0 representing population mean. Higher Z-scores indicate stronger bone density. Z-scores <-2.0 are considered low bone density for age. Height adjustments are made to account for short stature leading to falsely lower BMD Z-scores. | Mean | Standard Deviation | Z-score |
|
| Bone Mineral Density Femoral Neck | A bone mineral density (BMD) Z-score is an age, sex and race specific measurement. Normal BMD Z-scores range from -2.0 to 2.0 with 0.0 representing population mean. Higher Z-scores indicate stronger bone density. Z-scores <-2.0 are considered low bone density for age. Height adjustments are made to account for short stature leading to falsely lower BMD Z-scores. | Mean | Standard Deviation | Z-score |
|
| Screen for Child Anxiety Related Disorders (SCARED) | A 41 item self-report tool to assess for anxiety where each question receives a score of either 0, 1 or 2. Range of scores is 0 to 82. A total score of ≥ 25 may indicate the presence of an Anxiety Disorder. A higher score indicates there are more endorsed symptoms of anxiety | Mean | Standard Deviation | units on a scale |
|
| Children's Depression Inventory-II (CDI-2) | A 28 item self-report test to assess cognitive, affective and behavioral signs of depression in children and adolescents 7 to 17 years old. Scales include Emotional and Functional Problems, along with subscales of Negative mood/Physical symptoms, Negative Self-Esteem, Interpersonal Problems, and Ineffectiveness. The total score is converted into a T-score (mean=50, standard deviation=10) where a result >64 is considered elevated (range <40 to >90). A higher score indicates there are more endorsed symptoms of depression. | Mean | Standard Deviation | units on a scale |
|
| Child and Adolescent Memory Profile (CHaMP) Total Memory Index | The ChAMP is a norm-referenced test of memory and learning that was designed for use with children, adolescents, and young adults ranging from 5 through 21 years. The ChAMP includes four subtests that measure verbal and visual memory. The tests are administered by a trained professional. The total memory index score is the composite of these four subtests giving an overall estimate of memory with a mean score of 100, standard deviation of15, and range from 50-150. | Mean | Standard Deviation | units on a scale |
|
| Child Health Questionnaire (CHQ-87) Total Score | The CHQ-87 is an 87-item self-report survey is designed to measure the physical and psychosocial health of adolescents. The total score ranges from 0-100. Higher scores indicate better quality of life. This instrument is reliable and valid for evaluating aspects of health pertinent across age, gender, health condition, and socioeconomic status in adolescents. | Mean | Standard Deviation | units on a scale |
|
The control group reflects a comparison group similar to the Primary Ovarian Insufficiency (POI) patient group. As bone density, body composition, and cognitive domains continue to mature throughout the teenage years, this comparison group will provide an important metric of normal growth and development. |
| OG001 | POI Participants | This group includes participants diagnosed with POI who completed the transdermal estrogen titration. In an open-label fashion, participants with POI received Transdermal Estrogen (beginning at a dose of 25 μg/patch applied weekly), with the dose increased at 3, 6 12, and 18 months (to 37.5, 50, 75, and 100 µg/patch). |
|
|
| Secondary | Change in Dual Energy X-ray Absorptiometry (DXA) Measure of Bone Mineral Density (BMD) at the Whole Body Less Head, Total Hip, and Femoral Neck | To assess changes in bone mineral density DXA height adjusted BMD Z-scores of the whole body less head, total hip and femoral neck were measured. BMI, calcium intake, vitamin D intake and physical activity were included in the analysis. As DXA BMD Z-scores already include race, age, and sex, these variables were not included in the analysis. Z-scores ranging between -2.0 and 2.0 are considered normal. A Z-score <-2.0 is considered low. This analysis considers change in Z-score, therefore a high value reflects a greater increase in BMD Z-score. | One POI participant had prior oral contraceptive exposure, no matched control, and did not follow up for subsequent visits. For these reasons it was recommended that her data not be included in the analyses. | Posted | Least Squares Mean | Standard Deviation | Z-score | baseline to 24 months |
|
|
|
| Secondary | Change in Volumetric Bone Mineral Density (vBMD) at the Distal Radius as Measured by Peripheral Quantitative Computed Tomography (pQCT) | To assess the appendicular (peripheral) skeleton, pQCT (Stratec XCT 2000, Orthometrix, Inc., White Plains, NY) bone measures were obtained of the non-dominant radius at the 3% and 66% sites. Measurements were acquired with a voxel size of 0.4 mm, slice thickness of 2.3 mm, and scan speed of 25 mm/sec, and analyzed with manufacturer software version 6. | One POI participant had prior oral contraceptive exposure, no matched control, and did not follow up for subsequent visits. For these reasons it was recommended that her data not be included in the analyses. | Posted | Least Squares Mean | Standard Deviation | mg/mm^3 | Change from baseline to 24 months |
|
|
|
| Secondary | Anthropometrics | The mean BMI in kg/m^2 is presented for each study group at baseline and at the 24 months follow up visit to show that there was no significant difference between groups nor a significant change in BMI over the duration of the study. | Posted | Mean | Standard Deviation | kg/m^2 | Baseline and 24 months |
|
|
|
| Secondary | Change in Lean Mass as Measured by DXA Body Composition | Lean mass was obtained from the whole body DXA scan. Change in baseline to 24 months was assessed. | One POI participant had prior oral contraceptive exposure, no matched control, and did not follow up for subsequent visits. For these reasons it was recommended that her data not be included in the analyses. | Posted | Least Squares Mean | Standard Deviation | kg | Change in lean mass from baseline to 24 months |
|
|
|
| Secondary | Change in Symptoms of Anxiety as Measured by Screen for Child Anxiety Related Disorders (SCARED) | A 41 item self-report tool to assess for anxiety where each question receives a score of either 0, 1 or 2. Range of scores is 0 to 82. A total score of ≥ 25 may indicate the presence of an Anxiety Disorder. A higher score indicates there are more endorsed symptoms of anxiety. | One POI participant had prior oral contraceptive exposure, no matched control, and did not follow up for subsequent visits. For these reasons it was recommended that her data not be included in the analyses. | Posted | Least Squares Mean | Standard Deviation | score on a scale | Change from SCARED score baseline to 24 months |
|
|
|
| Secondary | Change in Symptoms of Depression as Measured by Child Depression Inventory-II (CDI-II) | A brief self-report test that helps assess cognitive, affective and behavioral signs of depression in children and adolescents 7 to 17 years old. Scales include Emotional and Functional Problems, along with subscales of Negative mood/Physical symptoms, Negative Self-Esteem, Interpersonal Problems, and Ineffectiveness. The total score is converted into a T-score (mean=50, standard deviation=10) where a result >64 is considered elevated. A higher score indicates there are more endorsed symptoms of depression. | One POI participant had prior oral contraceptive exposure, no matched control, and did not follow up for subsequent visits. For these reasons it was recommended that her data not be included in the analyses. | Posted | Least Squares Mean | Standard Deviation | T-score | Change from CDI-II score from baseline to 24 months |
|
|
|
| Secondary | Change in Memory as Assessed by the Children and Adolescent Memory Profile (CHAMP) Total Memory Index Score | The ChAMP is a norm-referenced test of memory and learning that was designed for use with children, adolescents, and young adults ranging from 5 through 21 years. The ChAMP includes 4 Subtests of visual and verbal memory to generate a total memory index score as a measure of overall memory. The total memory index score ranges from 50-150 with a mean=100 and standard deviation=15. Higher scores indicating better memory. The data presented here is the change in the total memory index score from baseline visit to the 24 month follow up time. | Posted | Least Squares Mean | Standard Deviation | score on a scale | Change from score from baseline to 24 months |
|
|
|
| Secondary | Change in Quality of Life as Assessed by the Child Health Questionnaire-Child Self-Report Form (CHQ-CF87) | The CHQ-87 is an 87-item self-report survey is designed to measure the physical and psychosocial health of adolescents. The total score ranges from 0-100. Higher scores indicate better quality of life. This instrument is reliable and valid for evaluating aspects of health pertinent across age, gender, health condition, and socioeconomic status in adolescents. | One POI participant had prior oral contraceptive exposure, no matched control, and did not follow up for subsequent visits. For these reasons it was recommended that her data not be included in the analyses. | Posted | Least Squares Mean | Standard Deviation | score on a scale | Change from baseline to 24 months |
|
|
|
| Secondary | Compliance With Transdermal Estrogen Patch | Participants with primary ovarian insufficiency (POI) were prescribed weekly transdermal estrogen (TDE2) patches and asked to log on a patch calendar when they changed the patch. Patch calendars were reviewed for compliance and weeks where at least one patch was applied were considered to be in compliance. Weeks in compliance generated the numerator whereas total weeks of participation in the study constituted the numerator. | As only participants with POI were prescribed TDE2 patches, we only report data on this cohort. | Posted | Mean | Standard Deviation | percentage of weeks with TDE2 use | Patch Calendars were collected at 6 months, 12 months, 18 months and 24 months. Data presented is through study completion. |
|
|
|
| Secondary | Study Medications - Serum Estradiol | Mean serum estradiol levels as measured in participants with POI. | The study was originally designed as a 12 month longitudinal trial. Subjects were given the option to continue for 24 months. One case participant declined the extension. As only participants with POI were prescribed transdermal estradiol patches, we only report data on this cohort. | Posted | Mean | Standard Deviation | pg/mL | Baseline, 12 months, 24 months |
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| 4 |
| 9 |
| EG001 | POI Participants | This group will be participants who have been recently diagnosed with POI. In an open-label fashion, participants with POI will receive Transdermal Estrogen (beginning at a dose of 25 μg/patch applied weekly), with the dose increased at 3, 6 12, and 18 months (to 37.5, 50, 75, and 100 µg/patch). For the reporting of adverse events, we included all participants who were enrolled in the study regardless of whether data on our primary or secondary outcomes were analyzed. | 0 | 10 | 1 | 10 | 8 | 10 |
| Diabetic ketoacidosis (DKA) hospitalization | Endocrine disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Suicidality | Psychiatric disorders | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Foot injury | Injury, poisoning and procedural complications | CTCAE (Unspecified) | Non-systematic Assessment | No fracture identified |
|
| Bronchitis | Infections and infestations | CTCAE (Unspecified) | Non-systematic Assessment |
|
| Breast Lump | Reproductive system and breast disorders | CTCAE (Unspecified) | Non-systematic Assessment | Fibroglandular tissue, normal ultrasound |
|
| Vasovagal Syncope | General disorders | CTCAE (Unspecified) | Non-systematic Assessment | During blood draw |
|
| Dental extraction | Surgical and medical procedures | CTCAE (Unspecified) | Non-systematic Assessment | Removal of wisdom teeth |
|
| Otoralgia | Ear and labyrinth disorders | CTCAE (Unspecified) | Non-systematic Assessment |
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| Motor Tics | Nervous system disorders | CTCAE (Unspecified) | Non-systematic Assessment | Patient with prior diagnosis of simple motor tics reported increased frequency of these events during course of participation in the study. |
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| Folliculitis | Injury, poisoning and procedural complications | CTCAE (Unspecified) | Non-systematic Assessment |
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| Diabetic ketoacidosis (DKA) | Endocrine disorders | CTCAE (Unspecified) | Non-systematic Assessment | Patient with known Type 1 Diabetes treated for DKA in emergency room setting. Did not require hospitalization. |
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| Insulin pump site malfunction | Endocrine disorders | CTCAE (Unspecified) | Non-systematic Assessment | Patient with known Type 1 Diabetes seen in local emergency department for insulin pump site malfunction. Resolved with typical care. She was not in DKA. |
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| Weight loss | General disorders | CTCAE (Unspecified) | Non-systematic Assessment |
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| Tympanoplasty | Surgical and medical procedures | CTCAE (Unspecified) | Non-systematic Assessment | Outpatient procedure for cholesteatoma |
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| Viral Illness | Infections and infestations | CTCAE (Unspecified) | Non-systematic Assessment |
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| Metatarsal fracture | Injury, poisoning and procedural complications | CTCAE (Unspecified) | Non-systematic Assessment |
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| Mood Changes | Social circumstances | CTCAE (Unspecified) | Non-systematic Assessment | Experienced when not wearing estrogen patch consistently |
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| Headache | Injury, poisoning and procedural complications | CTCAE (Unspecified) | Non-systematic Assessment |
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| Motor Vehicle Accident | General disorders | CTCAE (Unspecified) | Non-systematic Assessment |
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| Abdominal Pain | Injury, poisoning and procedural complications | CTCAE (Unspecified) | Non-systematic Assessment |
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| Excessive menstrual bleeding | Reproductive system and breast disorders | CTCAE (Unspecified) | Non-systematic Assessment | Menstrual bleeding stopped with norethindrone. Additional cycles were shorter in duration and lighter in flow. |
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Not provided
Not provided
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| Femoral Neck |
|
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| Estradiol 24 month |
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