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| ID | Type | Description | Link |
|---|---|---|---|
| K12HD001441-15 | U.S. NIH Grant/Contract | View source | |
| K23MH105569-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
| National Institute of Mental Health (NIMH) | NIH |
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Using neuroimaging, the investigator will study the effects of estrogen on mood and brain function in perimenopausal women either with or without depression.
Despite decades of research, affective disorders are prevalent and associated with significant morbidity and mortality. Unraveling the pathophysiology of affective disorders has been uniquely challenging because depressive syndromes are heterogeneous and have diverse etiologies. Thus, past studies aimed at identifying neural and genetic biomarkers that would improve the prediction of susceptibility, course of illness, and treatment response have yielded inconsistent results. The investigator proposes to address this problem by studying perimenopausal major depressive disorder (MDD), a depression subtype with a specific endocrine trigger (i.e., ovarian hormone withdrawal). Evidence supporting ovarian hormone withdrawal as a trigger for affective dysfunction in perimenopausal MDD includes the following: perimenopausal women show a temporal association between ovarian hormone withdrawal and the onset of mood symptoms; treatment with estrogen reduces mood symptoms; and blinded estradiol withdrawal re-precipitates depression in women with a history of perimenopausal MDD (manuscript in preparation). Focusing on perimenopausal MDD, a more homogeneous subtype with a specific endocrine trigger, will increase the likelihood of identifying meaningful neurobiological markers.One of the most powerful tools for understanding the neural mediators of MDD is brain imaging. Prior research suggests that the frontostriatal reward system is regulated by estradiol and implicated in MDD. However, neural mechanisms of perimenopausal MDD have never been studied. We will assess the neural reward system in perimenopausal women with and without MDD using functional magnetic resonance imaging (fMRI) at baseline and following estradiol treatment. The central hypothesis is that the neural reward system is hypoactive in perimenopausal MDD, and the antidepressant effects of a three-week transdermal estradiol intervention will be mediated by increased activity in the neural reward system, assessed using fMRI. The investigator will test the hypothesis by executing the following aims:
Aim 1: To measure the frontostriatal response to reward in perimenopausal MDD and test the effects of estradiol on neural activation in perimenopausal women. The investigator will use fMRI at baseline and following estradiol treatment in women with and without MDD to probe frontostriatal reward circuitry.
Aim 2: To quantify motivated behavior at baseline and following estradiol administration in perimenopausal women with and without MDD. Motivated behavior will be operationally defined as the response latency to reward versus non-reward during the fMRI reward task.
Aim 3: To measure the psychological correlates of the frontostriatal response to reward in women with perimenopausal MDD at baseline and following estradiol administration. Depressive symptoms will be assessed at baseline and following estradiol administration.
The results will provide critical information about the neuroendocrine pathophysiology of perimenopausal depression and may subsequently contribute to the development of novel pharmacologic interventions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Perimenopausal women, depressed | Experimental | Participants will receive transdermal estradiol (100μg/day) for 3 weeks. Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. |
|
| Perimenopausal women, non-depressed | Active Comparator | Participants will receive transdermal estradiol (100μg/day) for 3 weeks. Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Estradiol | Drug | Participants will receive transdermal estradiol (100μg/day) for 3 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Caudate Signal Intensity in Response to Reward During the MID fMRI Task at Pre-treatment | Caudate reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups at pre-treatment. | Pre-treatment (visit 3) |
| Nucleus Accumbens (NAcc) Signal Intensity in Response to Reward During the MID fMRI Task at Pre-treatment | Nucleus Accumbens (NAcc) reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups at pre-treatment. | Pre-treatment (visit 3) |
| Putamen Signal Intensity in Response to Reward During the MID fMRI Task at Pre-treatment | Putamen reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups at pre-treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Response Latency to Reward During the MID fMRI Task at Pre-treatment | Time (ms) between stimulus and response will be measured during the Monetary Incentive Delay (MID) task during the win trials. During MID the task, participants need to select the correct response during "win" and "lose" conditions by pressing a button on a button box in the MRI. | Pre-treatment (visit 3) |
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Inclusion Criteria:
Exclusion Criteria:
Patients will not be permitted to enter this protocol if they have any of the following:
current medication use (i.e., psychotropics, anti-hypertensives, statins, hormonal preparations, or frequent use of anti-inflammatory agents (> 10 times/month)). Women will be allowed to enroll who take medications without known mood effects (e.g. stable thyroid hormone replacement and occasional (< 5 times/month) use of Ambien)*;
pregnant, breastfeeding or trying to conceive;
FMP more than 12 months prior to enrollment;
history of undiagnosed vaginal bleeding;
undiagnosed enlargement of the ovaries;
polycystic ovary syndrome;
history of breast or ovarian cancer;
first degree relative with ovarian cancer;
first degree relative with premenopausal onset or bilateral breast cancer;
2+ first degree relatives with breast cancer (regardless of onset);
3+ relatives with postmenopausal breast cancer;
abnormal finding in a provider breast exam and/or mammogram;
known carrier of BRCA1 or 2 mutation;
endometriosis;
blood clots in the legs or lungs;
porphyria;
diabetes mellitus;
malignant melanoma;
Hodgkin's disease;
recurrent migraine headaches that are preceded by aura;
gallbladder or pancreatic disease**;
heart or kidney disease**;
liver disease;
cerebrovascular disease (stroke);
first degree relative with history of heart attack or stroke;
current cigarette smoking;
current suicidal ideation or psychosis;
past suicide attempts or psychotic episodes requiring hospitalization;
chronic depression (i.e., episode(s) lasting 3+ years);
recurrent depression (i.e., more than 1 prior episode, not including episodes with postpartum onset)
depressive episode(s) within 2 years of enrollment;
self-reported claustrophobia
peanut allergy
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| Name | Affiliation | Role |
|---|---|---|
| Crystal Schiller, PhD | University of North Carolina at Chapel Hill Psychiatry Department | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina | Chapel Hill | North Carolina | 27514 | United States |
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Enrolled participants were excluded prior to the start of study intervention due to: exclusionary psychiatric history (i.e. substance abuse, past hypomania, persistent depression), exclusionary gynecological history (i.e. fibroids, abnormal pap), exclusionary medical history (i.e. abnormal lab values), exclusionary medication, and imaging concerns.
The recruitment process included, social media advertising using Facebook, Instagram, and Craigslist; mass emailing using university wide emails and a database of select University of North Carolina (UNC) healthcare patients (Carolina data warehouse); and flyer advertisements placed in university buildings and local businesses.
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| ID | Title | Description |
|---|---|---|
| FG000 | Perimenopausal Women, Depressed | Participants will receive transdermal estradiol (100μg/day) for 3 weeks. Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. Estradiol: Participants will receive transdermal estradiol (100μg/day) for 3 weeks Progesterone: Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. |
| FG001 | Perimenopausal Women, Non-depressed | Participants will receive transdermal estradiol (100μg/day) for 3 weeks. Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. Estradiol: Participants will receive transdermal estradiol (100μg/day) for 3 weeks Progesterone: Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Perimenopausal Women, Depressed | Participants will receive transdermal estradiol (100μg/day) for 3 weeks. Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. Estradiol: Participants will receive transdermal estradiol (100μg/day) for 3 weeks Progesterone: Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. |
| 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 | Caudate Signal Intensity in Response to Reward During the MID fMRI Task at Pre-treatment | Caudate reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups at pre-treatment. | Posted | Mean | Standard Deviation | percent signal change | Pre-treatment (visit 3) |
|
Adverse event data was tracked over a participants time in the protocol (1 month), all unresolved adverse events were tracked by the investigator until the events were resolved, the subject was lost to follow-up, or the adverse event was otherwise explained.
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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 | Perimenopausal Women, Depressed | Participants will receive transdermal estradiol (100μg/day) for 3 weeks. Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. Estradiol: Participants will receive transdermal estradiol (100μg/day) for 3 weeks Progesterone: Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Itchiness at patch site | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Crystal Edler Schiller, PhD | UNC School of Medicine | 919-966-4810 | crystal_schiller@med.unc.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 | Apr 12, 2016 | Sep 25, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003863 | Depression |
| D019964 | Mood Disorders |
| D003866 | Depressive Disorder |
| D001523 | Mental Disorders |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D004958 | Estradiol |
| D011374 | Progesterone |
| ID | Term |
|---|---|
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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|
| Progesterone | Drug | Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. |
|
|
| Pre-treatment (visit 3) |
| Caudate Signal Intensity in Response to Reward During the MID fMRI Task Following Estradiol Treatment. | Caudate reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups following treatment. | Post-treatment (visit 6) |
| Nucleus Accumbens (NAcc) Signal Intensity in Response to Reward During the MID fMRI Task Following Estradiol Treatment. | Nucleus accumbens (NAcc) reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups following treatment. | Post-treatment (visit 6) |
| Putamen Signal Intensity in Response to Reward During the MID fMRI Task Following Estradiol Treatment. | Putamen reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups following treatment. | Post-treatment (visit 6) |
| Response Latency to Reward During the MID fMRI Task Following Estradiol Treatment | Time (ms) between stimulus and response will be measured during reward trials of the Monetary Incentive Delay (MID) task. During MID the task, participants need to select the correct response during "win" and "lose" conditions by pressing a button on a button box in the MRI. | Post-treatment (visit 6) |
| Change in Inventory of Depression and Anxiety Symptoms (IDAS) Dysphoria Scores | The Dysphoria Scale of the Inventory of Depression and Anxiety Symptoms (IDAS) will be used to assess the change in depressive symptom severity. The IDAS Dysphoria Scale consists of 10 items and uses a 5-point Likert-type scale, ranging from 1 to 5 with 1 indicating "not at all" and 5 indicating "extremely". As such, the range of possible scores is 10 to 50. The Dysphoria scale includes items assessing feelings of depression, inadequacy, psychomotor agitation, guilt, discouragement, anhedonia, poor concentration, difficulty with decision-making, psychomotor retardation, and worry. Higher scores indicate worse depression symptoms. | Assessed at pre- and post-treatment (visits 3 and 6) |
| BG001 | Perimenopausal Women, Non-depressed | Participants will receive transdermal estradiol (100μg/day) for 3 weeks. Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. Estradiol: Participants will receive transdermal estradiol (100μg/day) for 3 weeks Progesterone: Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
Participants will receive transdermal estradiol (100μg/day) for 3 weeks. Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. Estradiol: Participants will receive transdermal estradiol (100μg/day) for 3 weeks Progesterone: Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. |
| OG001 | Perimenopausal Women, Non-depressed | Participants will receive transdermal estradiol (100μg/day) for 3 weeks. Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. Estradiol: Participants will receive transdermal estradiol (100μg/day) for 3 weeks Progesterone: Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. |
|
|
|
| Primary | Nucleus Accumbens (NAcc) Signal Intensity in Response to Reward During the MID fMRI Task at Pre-treatment | Nucleus Accumbens (NAcc) reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups at pre-treatment. | Posted | Mean | Standard Deviation | percent signal change | Pre-treatment (visit 3) |
|
|
|
|
| Primary | Putamen Signal Intensity in Response to Reward During the MID fMRI Task at Pre-treatment | Putamen reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups at pre-treatment. | Posted | Mean | Standard Deviation | percent signal change | Pre-treatment (visit 3) |
|
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|
|
| Primary | Caudate Signal Intensity in Response to Reward During the MID fMRI Task Following Estradiol Treatment. | Caudate reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups following treatment. | Posted | Mean | Standard Deviation | percent signal change | Post-treatment (visit 6) |
|
|
|
|
| Primary | Nucleus Accumbens (NAcc) Signal Intensity in Response to Reward During the MID fMRI Task Following Estradiol Treatment. | Nucleus accumbens (NAcc) reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups following treatment. | Posted | Mean | Standard Deviation | percent signal change | Post-treatment (visit 6) |
|
|
|
|
| Primary | Putamen Signal Intensity in Response to Reward During the MID fMRI Task Following Estradiol Treatment. | Putamen reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups following treatment. | Posted | Mean | Standard Deviation | percent signal change | Post-treatment (visit 6) |
|
|
|
|
| Secondary | Response Latency to Reward During the MID fMRI Task at Pre-treatment | Time (ms) between stimulus and response will be measured during the Monetary Incentive Delay (MID) task during the win trials. During MID the task, participants need to select the correct response during "win" and "lose" conditions by pressing a button on a button box in the MRI. | Posted | Mean | Standard Deviation | Milliseconds | Pre-treatment (visit 3) |
|
|
|
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| Secondary | Response Latency to Reward During the MID fMRI Task Following Estradiol Treatment | Time (ms) between stimulus and response will be measured during reward trials of the Monetary Incentive Delay (MID) task. During MID the task, participants need to select the correct response during "win" and "lose" conditions by pressing a button on a button box in the MRI. | Posted | Mean | Standard Deviation | Milliseconds | Post-treatment (visit 6) |
|
|
|
|
| Secondary | Change in Inventory of Depression and Anxiety Symptoms (IDAS) Dysphoria Scores | The Dysphoria Scale of the Inventory of Depression and Anxiety Symptoms (IDAS) will be used to assess the change in depressive symptom severity. The IDAS Dysphoria Scale consists of 10 items and uses a 5-point Likert-type scale, ranging from 1 to 5 with 1 indicating "not at all" and 5 indicating "extremely". As such, the range of possible scores is 10 to 50. The Dysphoria scale includes items assessing feelings of depression, inadequacy, psychomotor agitation, guilt, discouragement, anhedonia, poor concentration, difficulty with decision-making, psychomotor retardation, and worry. Higher scores indicate worse depression symptoms. | Posted | Mean | Standard Error | score on a scale | Assessed at pre- and post-treatment (visits 3 and 6) |
|
|
|
|
| 0 |
| 33 |
| 0 |
| 33 |
| 16 |
| 33 |
| EG001 | Perimenopausal Women, Non-depressed | Participants will receive transdermal estradiol (100μg/day) for 3 weeks. Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. Estradiol: Participants will receive transdermal estradiol (100μg/day) for 3 weeks Progesterone: Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation. | 0 | 31 | 0 | 31 | 17 | 31 |
| Headaches | Nervous system disorders | Non-systematic Assessment |
|
| Breast Tenderness | Reproductive system and breast disorders | Non-systematic Assessment | Breast fullness or tenderness. |
|
| Cramps | Reproductive system and breast disorders | Non-systematic Assessment | menstrual type cramps, abdominal pain and tenderness, sensitive groin |
|
| Bloating | Endocrine disorders | Non-systematic Assessment | Water retention or bloating |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | Non-systematic Assessment |
|
| Menstrual Bleeding | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Hot Flashes | Endocrine disorders | Non-systematic Assessment |
|
| Waking during the night | General disorders | Non-systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Lower Back Pain | General disorders | Non-systematic Assessment |
|
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| D011083 |
| Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D003339 | Corpus Luteum Hormones |
| D045167 | Progesterone Congeners |