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| ID | Type | Description | Link |
|---|---|---|---|
| R21AG054955 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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The primary aim of this study is to test whether type 2 diabetes interacts with estradiol on brain metabolism in vivo in humans. This will be accomplished by imaging brain metabolism using positron emission tomography before and after short-term administration of transdermal 17β-estradiol in 10 postmenopausal women with diabetes and 10 non-diabetic postmenopausal women.
Epidemiological studies suggest there may be an interaction between type 2 diabetes and estrogen in postmenopausal women, such that diabetes may interact with estrogen levels over time to increase risk for dementia. The mechanism for this effect is now known. However, animal research suggests that it may occur through estrogen's effects on cellular metabolism of glucose and ketone bodies. The primary aim of this study is to test whether type 2 diabetes interacts with estradiol on brain metabolism in vivo in humans. This will be accomplished by imaging brain metabolism using positron emission tomography before and after short-term administration of transdermal 17β-estradiol in 10 postmenopausal women with diabetes and 10 non-diabetic postmenopausal women.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Post menopausal women with diabetes | Experimental | 8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women with type 2 diabetes |
|
| Post menopausal women without diabetes | Experimental | 8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women without type 2 diabetes. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Estradiol patch | Drug | transdermal 17β-estradiol patch |
|
| Measure | Description | Time Frame |
|---|---|---|
| Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)--Whole Brain | Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG will be quantified. | Baseline |
| FDG PET--Whole Brain | Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG will be quantified. | Week 8 |
| Acetoacetate Uptake (AcAc) PET--Whole Brain | Brain metabolism will be measured using PET tracers to examine brain ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of AcAc tracers will be quantified. | Baseline |
| AcAc PET--Whole Brain | Brain metabolism will be measured using PET tracers to examine brain ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of AcAc tracers will be quantified. | Week 8 |
| Change in Uptake of Glucose and Ketone Bodies in Whole Brain and Alzheimer's Disease-related Regions of Interest. | Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET) and ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG and AcAc tracers will be quantified, as well as uptake of AcAc relative to FDG to find potential regions of compensatory ketone use |
| Measure | Description | Time Frame |
|---|---|---|
| Short-Term Memory Composite Score | A composite memory score was created by averaging z-scores for CVLT delayed recall, BVRT delayed recall, and prospective memory. A composite executive function score was created by averaging digit span forwards total correct, digit span backwards total correct, and both verbal fluency scores. Summed z-score ranging from -2 to 2 where higher score indicates better performance. |
| Measure | Description | Time Frame |
|---|---|---|
| Regional Ratio of Ketone/Glucose Uptake | Baseline and Week 8 | |
| Number of White Matter Hypertensities | Attained from a T2-weighted FLAIR image, an indicator of small-vessel disease correlated with diabetes status and hypertension |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christina Hugenschmidt, PhD | Wake Forest Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wake Forest University Health Sciences | Winston-Salem | North Carolina | 27157 | United States |
Undecided at the present time.
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| ID | Title | Description |
|---|---|---|
| FG000 | Post Menopausal Women With Diabetes | 8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women with type 2 diabetes Estradiol patch: transdermal 17β-estradiol patch |
| FG001 | Post Menopausal Women Without Diabetes | 8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women without type 2 diabetes. Estradiol patch: transdermal 17β-estradiol patch |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Post Menopausal Women With Diabetes | 8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women with type 2 diabetes Estradiol patch: transdermal 17β-estradiol patch |
| BG001 | Post Menopausal Women Without Diabetes |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)--Whole Brain | Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG will be quantified. | Non-Diabetes: n=2, technical error resulted in issues reconstructing PET images for one participant. Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | micromoles/min/100g tissue | Baseline |
|
8 weeks
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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 | Post Menopausal Women Without Diabetes | 8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women without type 2 diabetes. Estradiol patch: transdermal 17β-estradiol patch |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated Blood Pressure | Vascular disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christina Hugenschmidt, PhD | Wake Forest University Health Science | 336.713.4190 | chugensc@wakehealth.edu |
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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 | Mar 16, 2021 | Jul 15, 2022 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 19, 2021 | Sep 24, 2021 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D003704 | Dementia |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C511292 | Ortho Evra |
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Primary Objective: The primary objective is to determine whether the effects of glucose and ketone body uptake to the brain in response to 8-week administration of transdermal 17β-estradiol differ in postmenopausal women with and without type 2 diabetes.
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| Baseline and 8 weeks |
| Baseline and Week 8 |
| Executive Function Composite Score | The California Verbal Learning Test (CVLT) is a word list recall task that can be used to test immediate and delayed verbal memory. Free recall after the short delay (immediately after learning lists) and long delay (25 minutes) are reported. Summed z-score ranging from -2 to 2 where higher score indicates better performance. | Baseline and Week 8 |
| California Verbal Learning Task (CVLT) Long Delay Free Recall | The CVLT is a word list recall task that can be used to test immediate and delayed verbal memory. Free recall after long delay (25 minutes). The minimum score is 0. The maximum score is 16 and a higher score represents better performance. | Baseline and Week 8 |
| CVLT Short Delay Free Recall | The CVLT is a word list recall task that can be used to test immediate and delayed verbal memory. Short delay free recall is immediately after learning lists. The minimum score is 0. The maximum score is 16 and a higher score represents better performance. | Baseline and Week 8 |
| Benton Visual Retention Task (BVRT) Total Score | The BVRT tests figural memory by testing memory for a line drawing. The minimum score is 0. The scoring used is total correct, the maximum score is 10, and a higher score represents better performance. The total score is reported. | Baseline and Week 8 |
| Prospective Memory | The Prospective Memory test is a test of everyday memory where participants are given instructions for 3 tasks that will occur later on during the testing session. The minimum score is 0. The maximum score is 12 points, a higher score represents better performance, and the total score is reported | Baseline and Week 8 |
| Verbal Fluency (Letters) | Participants were given a letter and asked to say aloud as many words as they could think of beginning with that letter. The three letters were F, A, and S, and the participant had one minute per letter to list words. The total score reported is the sum of the correct words generated for all three letters. Although there is no set maximum score, based on published data, it was anticipated that scores could range from 1 to no more than 120. A higher value reflects better performance. | Baseline and Week 8 |
| Verbal Fluency Score (Fruits and Vegetables) | Participants were given one minute to say aloud as many fruits as possible and one minute to list as many vegetables as possible. The total score reported is the sum of all correct fruits and vegetables listed. Although there is no set maximum score, it was anticipated that scores could range from 0 to no more than 60. A higher value reflects better performance. | Baseline and Week 8 |
| Digit Span Forward Total Correct | Participants listened to a sequence of two to nine numbers and were asked to repeat each sequence back to the tester in the same order the numbers were presented. The outcome measure reported here is the total number of correct responses (range of scores 0-9). Higher scores reflect better performance. | Baseline and Week 8 |
| Digit Span Backward Total Correct | Participants listened to a sequence of two to nine numbers and were asked to repeat each sequence back to the tester in reverse order. The outcome measure reported here is the longest span of numbers recalled (range of scores 0-9). Higher scores reflect better performance. | Baseline and Week 8 |
| Finger Tapping Score--Dominant Hand | The Finger Tapping test assesses fine motor speed by asking participants to tap a button as many times as possible. Seven trials were administered. The highest and lowest scores were dropped, and the reported score is the average of the remaining 5 trials. Results for the dominant hand are reported here. There is no set maximum score. However, published averages for women in this age range suggest that a value over 57 would be highly unusual. A higher value (more taps) is better performance. | Baseline and Week 8 |
| Finger Tapping Score--Non-Dominant Hand | The Finger Tapping test assesses fine motor speed by asking participants to tap a button as many times as possible. Seven trials were administered. The highest and lowest scores were dropped, and the reported score is the average of the remaining 5 trials. Results for the non-dominant hand are reported here. There is no set maximum score. However, published averages for women in this age range suggest that a value over 57 would be highly unusual. A higher value (more taps) is better performance. | Baseline and Week 8 |
| Card Rotations Test Score | The Card Rotations Test is used to assess the ability to mentally rotate figures in space. The test has two parts, each of which last 3 minutes. During each part, the participant is given a sheet of paper with 10 simple geometric figures. Next to each figure is a row of 8 similar figures. Participants are asked to mark whether each of the figures in the row is the same or different than the first figure in the row. The score reported is the number of correct responses. The minimum score is 0. The maximum possible score is 160 and a higher score reflects better performance. | Baseline and Week 8 |
| Change in Short-term Memory and Executive Function Composite Scores. | A battery of cognitive tasks will be administered before and after estrogen administration. Composite z-scores will be calculated by calculating a z-score for each cognitive task and summing z-scores from -5 (low) to 5 (high) for the tasks designated as short-term memory and executive function.Higher scores denotes better outcomes. | Baseline and 8 weeks |
| Baseline and Week 8 |
| Number of Microbleeds | Attained from a susceptibility-weighted image | Baseline and Week 8 |
| veins would not stay open during the PET scan. |
|
8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women without type 2 diabetes. Estradiol patch: transdermal 17β-estradiol patch |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Post Menopausal Women With Diabetes |
8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women with type 2 diabetes Estradiol patch: transdermal 17β-estradiol patch |
|
|
| Primary | FDG PET--Whole Brain | Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG will be quantified. | Non-Diabetes: n=2, technical error resulted in issues reconstructing PET images for one participant. Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | micromoles/min/100g tissue | Week 8 |
|
|
|
| Primary | Acetoacetate Uptake (AcAc) PET--Whole Brain | Brain metabolism will be measured using PET tracers to examine brain ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of AcAc tracers will be quantified. | Non-Diabetes: n=2, technical error resulted in issues reconstructing PET images for one participant. Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | micromoles/min/100g tissue | Baseline |
|
|
|
| Primary | AcAc PET--Whole Brain | Brain metabolism will be measured using PET tracers to examine brain ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of AcAc tracers will be quantified. | Non-Diabetes: n=2, technical error resulted in issues reconstructing PET images for one participant. Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | micromoles/min/100g tissue | Week 8 |
|
|
|
| Primary | Change in Uptake of Glucose and Ketone Bodies in Whole Brain and Alzheimer's Disease-related Regions of Interest. | Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET) and ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG and AcAc tracers will be quantified, as well as uptake of AcAc relative to FDG to find potential regions of compensatory ketone use | This outcome measure is actually many outcome measures. It was broken down into the other four primary outcome measures listed, so no no results will be listed here. Also, rather than "change in", results will be reported as mean/standard deviation in the other outcomes. | Posted | Baseline and 8 weeks |
|
|
| Secondary | Short-Term Memory Composite Score | A composite memory score was created by averaging z-scores for CVLT delayed recall, BVRT delayed recall, and prospective memory. A composite executive function score was created by averaging digit span forwards total correct, digit span backwards total correct, and both verbal fluency scores. Summed z-score ranging from -2 to 2 where higher score indicates better performance. | Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | z-score | Baseline and Week 8 |
|
|
|
| Secondary | Executive Function Composite Score | The California Verbal Learning Test (CVLT) is a word list recall task that can be used to test immediate and delayed verbal memory. Free recall after the short delay (immediately after learning lists) and long delay (25 minutes) are reported. Summed z-score ranging from -2 to 2 where higher score indicates better performance. | Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | z-score | Baseline and Week 8 |
|
|
|
| Secondary | California Verbal Learning Task (CVLT) Long Delay Free Recall | The CVLT is a word list recall task that can be used to test immediate and delayed verbal memory. Free recall after long delay (25 minutes). The minimum score is 0. The maximum score is 16 and a higher score represents better performance. | Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 8 |
|
|
|
| Secondary | CVLT Short Delay Free Recall | The CVLT is a word list recall task that can be used to test immediate and delayed verbal memory. Short delay free recall is immediately after learning lists. The minimum score is 0. The maximum score is 16 and a higher score represents better performance. | Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 8 |
|
|
|
| Secondary | Benton Visual Retention Task (BVRT) Total Score | The BVRT tests figural memory by testing memory for a line drawing. The minimum score is 0. The scoring used is total correct, the maximum score is 10, and a higher score represents better performance. The total score is reported. | Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 8 |
|
|
|
| Secondary | Prospective Memory | The Prospective Memory test is a test of everyday memory where participants are given instructions for 3 tasks that will occur later on during the testing session. The minimum score is 0. The maximum score is 12 points, a higher score represents better performance, and the total score is reported | Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 8 |
|
|
|
| Secondary | Verbal Fluency (Letters) | Participants were given a letter and asked to say aloud as many words as they could think of beginning with that letter. The three letters were F, A, and S, and the participant had one minute per letter to list words. The total score reported is the sum of the correct words generated for all three letters. Although there is no set maximum score, based on published data, it was anticipated that scores could range from 1 to no more than 120. A higher value reflects better performance. | Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | number of correct words generated | Baseline and Week 8 |
|
|
|
| Secondary | Verbal Fluency Score (Fruits and Vegetables) | Participants were given one minute to say aloud as many fruits as possible and one minute to list as many vegetables as possible. The total score reported is the sum of all correct fruits and vegetables listed. Although there is no set maximum score, it was anticipated that scores could range from 0 to no more than 60. A higher value reflects better performance. | Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | number of correct fruits and vegetables | Baseline and Week 8 |
|
|
|
| Secondary | Digit Span Forward Total Correct | Participants listened to a sequence of two to nine numbers and were asked to repeat each sequence back to the tester in the same order the numbers were presented. The outcome measure reported here is the total number of correct responses (range of scores 0-9). Higher scores reflect better performance. | Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | number of correct responses | Baseline and Week 8 |
|
|
|
| Secondary | Digit Span Backward Total Correct | Participants listened to a sequence of two to nine numbers and were asked to repeat each sequence back to the tester in reverse order. The outcome measure reported here is the longest span of numbers recalled (range of scores 0-9). Higher scores reflect better performance. | Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | span of numbers recalled | Baseline and Week 8 |
|
|
|
| Secondary | Finger Tapping Score--Dominant Hand | The Finger Tapping test assesses fine motor speed by asking participants to tap a button as many times as possible. Seven trials were administered. The highest and lowest scores were dropped, and the reported score is the average of the remaining 5 trials. Results for the dominant hand are reported here. There is no set maximum score. However, published averages for women in this age range suggest that a value over 57 would be highly unusual. A higher value (more taps) is better performance. | Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | number of taps | Baseline and Week 8 |
|
|
|
| Secondary | Finger Tapping Score--Non-Dominant Hand | The Finger Tapping test assesses fine motor speed by asking participants to tap a button as many times as possible. Seven trials were administered. The highest and lowest scores were dropped, and the reported score is the average of the remaining 5 trials. Results for the non-dominant hand are reported here. There is no set maximum score. However, published averages for women in this age range suggest that a value over 57 would be highly unusual. A higher value (more taps) is better performance. | Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | number of taps | Baseline and Week 8 |
|
|
|
| Secondary | Card Rotations Test Score | The Card Rotations Test is used to assess the ability to mentally rotate figures in space. The test has two parts, each of which last 3 minutes. During each part, the participant is given a sheet of paper with 10 simple geometric figures. Next to each figure is a row of 8 similar figures. Participants are asked to mark whether each of the figures in the row is the same or different than the first figure in the row. The score reported is the number of correct responses. The minimum score is 0. The maximum possible score is 160 and a higher score reflects better performance. | Results only reported for subjects who completed study. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 8 |
|
|
|
| Secondary | Change in Short-term Memory and Executive Function Composite Scores. | A battery of cognitive tasks will be administered before and after estrogen administration. Composite z-scores will be calculated by calculating a z-score for each cognitive task and summing z-scores from -5 (low) to 5 (high) for the tasks designated as short-term memory and executive function.Higher scores denotes better outcomes. | This outcome should have been separated into many other outcomes. So we have separated out all the scores and results will be reported in the other separated memory and executive function score outcomes. No results will be reported in this outcome. Also, rather than "change in", results will be reported as mean/standard deviation in the other outcomes. | Posted | Baseline and 8 weeks |
|
|
| Other Pre-specified | Regional Ratio of Ketone/Glucose Uptake | Not Posted | Baseline and Week 8 | Participants |
| Other Pre-specified | Number of White Matter Hypertensities | Attained from a T2-weighted FLAIR image, an indicator of small-vessel disease correlated with diabetes status and hypertension | Not Posted | Baseline and Week 8 | Participants |
| Other Pre-specified | Number of Microbleeds | Attained from a susceptibility-weighted image | Not Posted | Baseline and Week 8 | Participants |
| 0 |
| 4 |
| 0 |
| 4 |
| 2 |
| 4 |
| EG001 | Post Menopausal Women With Diabetes | 8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women with type 2 diabetes Estradiol patch: transdermal 17β-estradiol patch | 0 | 8 | 0 | 8 | 7 | 8 |
| Started Period-Like Bleeding/Spotting | Reproductive system and breast disorders | Systematic Assessment |
|
| Breast Tenderness/Soreness | Reproductive system and breast disorders | Systematic Assessment |
|
| Cramping | Reproductive system and breast disorders | Systematic Assessment |
|
| Itching Around Drug Patch | Product Issues | Systematic Assessment |
|
| Pneumonia | Infections and infestations | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Vaginal Dryness | Reproductive system and breast disorders | Systematic Assessment |
|
| Fall at Home | Injury, poisoning and procedural complications | Systematic Assessment |
|
Not provided
Not provided
| D004700 | Endocrine System Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |