Trial Outcomes & Findings for Perimenopausal Effects of Estradiol on Reward Responsiveness (NCT NCT02255175)
NCT ID: NCT02255175
Last Updated: 2019-11-12
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
64 participants
Primary outcome timeframe
Pre-treatment (visit 3)
Results posted on
2019-11-12
Participant Flow
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.
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.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
33
|
31
|
|
Overall Study
COMPLETED
|
16
|
19
|
|
Overall Study
NOT COMPLETED
|
17
|
12
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Perimenopausal Effects of Estradiol on Reward Responsiveness
Baseline characteristics by cohort
| Measure |
Perimenopausal Women, Depressed
n=33 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.
|
Perimenopausal Women, Non-depressed
n=31 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.
|
Total
n=64 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
Age
|
50.13 years
n=5 Participants
|
50.76 years
n=7 Participants
|
50.44 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
64 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · White or Caucasion
|
23 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Black or African American
|
8 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Multi-Racial
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race/Ethnicity · Cuban or Carribean
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-treatment (visit 3)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.
Outcome measures
| Measure |
Perimenopausal Women, Depressed
n=16 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.
|
Perimenopausal Women, Non-depressed
n=19 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.
|
Perimenopausal Women, Depressed, Following Estradiol Treatment
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.
|
Perimenopausal Women, Non-depressed, Following Estradiol
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.
|
|---|---|---|---|---|
|
Caudate Signal Intensity in Response to Reward During the MID fMRI Task at Pre-treatment
|
.027 percent signal change
Standard Deviation .105
|
.043 percent signal change
Standard Deviation .074
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-treatment (visit 3)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.
Outcome measures
| Measure |
Perimenopausal Women, Depressed
n=16 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.
|
Perimenopausal Women, Non-depressed
n=19 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.
|
Perimenopausal Women, Depressed, Following Estradiol Treatment
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.
|
Perimenopausal Women, Non-depressed, Following Estradiol
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.
|
|---|---|---|---|---|
|
Nucleus Accumbens (NAcc) Signal Intensity in Response to Reward During the MID fMRI Task at Pre-treatment
|
.045 percent signal change
Standard Deviation .117
|
.052 percent signal change
Standard Deviation .108
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-treatment (visit 3)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.
Outcome measures
| Measure |
Perimenopausal Women, Depressed
n=16 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.
|
Perimenopausal Women, Non-depressed
n=19 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.
|
Perimenopausal Women, Depressed, Following Estradiol Treatment
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.
|
Perimenopausal Women, Non-depressed, Following Estradiol
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.
|
|---|---|---|---|---|
|
Putamen Signal Intensity in Response to Reward During the MID fMRI Task at Pre-treatment
|
.015 percent signal change
Standard Deviation .103
|
.004 percent signal change
Standard Deviation .093
|
—
|
—
|
PRIMARY outcome
Timeframe: Post-treatment (visit 6)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.
Outcome measures
| Measure |
Perimenopausal Women, Depressed
n=16 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.
|
Perimenopausal Women, Non-depressed
n=19 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.
|
Perimenopausal Women, Depressed, Following Estradiol Treatment
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.
|
Perimenopausal Women, Non-depressed, Following Estradiol
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.
|
|---|---|---|---|---|
|
Caudate Signal Intensity in Response to Reward During the MID fMRI Task Following Estradiol Treatment.
|
.005 percent signal change
Standard Deviation .079
|
.026 percent signal change
Standard Deviation .103
|
—
|
—
|
PRIMARY outcome
Timeframe: Post-treatment (visit 6)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.
Outcome measures
| Measure |
Perimenopausal Women, Depressed
n=16 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.
|
Perimenopausal Women, Non-depressed
n=19 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.
|
Perimenopausal Women, Depressed, Following Estradiol Treatment
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.
|
Perimenopausal Women, Non-depressed, Following Estradiol
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.
|
|---|---|---|---|---|
|
Nucleus Accumbens (NAcc) Signal Intensity in Response to Reward During the MID fMRI Task Following Estradiol Treatment.
|
.040 percent signal change
Standard Deviation .110
|
.059 percent signal change
Standard Deviation .118
|
—
|
—
|
PRIMARY outcome
Timeframe: Post-treatment (visit 6)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.
Outcome measures
| Measure |
Perimenopausal Women, Depressed
n=16 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.
|
Perimenopausal Women, Non-depressed
n=19 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.
|
Perimenopausal Women, Depressed, Following Estradiol Treatment
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.
|
Perimenopausal Women, Non-depressed, Following Estradiol
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.
|
|---|---|---|---|---|
|
Putamen Signal Intensity in Response to Reward During the MID fMRI Task Following Estradiol Treatment.
|
-.030 percent signal change
Standard Deviation .068
|
.032 percent signal change
Standard Deviation .073
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-treatment (visit 3)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.
Outcome measures
| Measure |
Perimenopausal Women, Depressed
n=16 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.
|
Perimenopausal Women, Non-depressed
n=19 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.
|
Perimenopausal Women, Depressed, Following Estradiol Treatment
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.
|
Perimenopausal Women, Non-depressed, Following Estradiol
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.
|
|---|---|---|---|---|
|
Response Latency to Reward During the MID fMRI Task at Pre-treatment
|
204.17 Milliseconds
Standard Deviation 25.11
|
209.63 Milliseconds
Standard Deviation 20.71
|
—
|
—
|
SECONDARY outcome
Timeframe: Post-treatment (visit 6)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.
Outcome measures
| Measure |
Perimenopausal Women, Depressed
n=16 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.
|
Perimenopausal Women, Non-depressed
n=19 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.
|
Perimenopausal Women, Depressed, Following Estradiol Treatment
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.
|
Perimenopausal Women, Non-depressed, Following Estradiol
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.
|
|---|---|---|---|---|
|
Response Latency to Reward During the MID fMRI Task Following Estradiol Treatment
|
190.68 Milliseconds
Standard Deviation 34.98
|
193.43 Milliseconds
Standard Deviation 39.60
|
—
|
—
|
SECONDARY outcome
Timeframe: Assessed at pre- and post-treatment (visits 3 and 6)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.
Outcome measures
| Measure |
Perimenopausal Women, Depressed
n=16 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.
|
Perimenopausal Women, Non-depressed
n=19 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.
|
Perimenopausal Women, Depressed, Following Estradiol Treatment
n=16 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.
|
Perimenopausal Women, Non-depressed, Following Estradiol
n=19 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.
|
|---|---|---|---|---|
|
Change in Inventory of Depression and Anxiety Symptoms (IDAS) Dysphoria Scores
|
24.56 score on a scale
Standard Error 1.47
|
13.79 score on a scale
Standard Error 1.35
|
15.25 score on a scale
Standard Error 1.13
|
11.84 score on a scale
Standard Error 1.04
|
Adverse Events
Perimenopausal Women, Depressed
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Perimenopausal Women, Non-depressed
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Perimenopausal Women, Depressed
n=33 participants at risk
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.
|
Perimenopausal Women, Non-depressed
n=31 participants at risk
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.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Itchiness at patch site
|
15.2%
5/33 • Number of events 5 • 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.
|
12.9%
4/31 • Number of events 4 • 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.
|
|
Nervous system disorders
Headaches
|
12.1%
4/33 • Number of events 4 • 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.
|
12.9%
4/31 • Number of events 4 • 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.
|
|
Reproductive system and breast disorders
Breast Tenderness
|
18.2%
6/33 • Number of events 6 • 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.
|
9.7%
3/31 • Number of events 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.
|
|
Reproductive system and breast disorders
Cramps
|
15.2%
5/33 • Number of events 5 • 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.
|
9.7%
3/31 • Number of events 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.
|
|
Endocrine disorders
Bloating
|
6.1%
2/33 • Number of events 2 • 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.
|
6.5%
2/31 • Number of events 2 • 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.
|
|
Gastrointestinal disorders
Nausea
|
9.1%
3/33 • Number of events 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.
|
6.5%
2/31 • Number of events 2 • 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.
|
|
Nervous system disorders
Dizziness
|
3.0%
1/33 • Number of events 1 • 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.
|
6.5%
2/31 • Number of events 2 • 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.
|
|
Reproductive system and breast disorders
Menstrual Bleeding
|
6.1%
2/33 • Number of events 2 • 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.
|
6.5%
2/31 • Number of events 2 • 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.
|
|
Endocrine disorders
Hot Flashes
|
6.1%
2/33 • Number of events 2 • 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.
|
3.2%
1/31 • Number of events 1 • 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.
|
|
General disorders
Waking during the night
|
0.00%
0/33 • 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.
|
6.5%
2/31 • Number of events 2 • 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.
|
|
Skin and subcutaneous tissue disorders
Acne
|
6.1%
2/33 • Number of events 2 • 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.
|
0.00%
0/31 • 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.
|
|
General disorders
Lower Back Pain
|
6.1%
2/33 • Number of events 2 • 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.
|
0.00%
0/31 • 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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place