Trial Outcomes & Findings for Early Menopause Hormone Treatment and Cognition (NCT NCT01046643)
NCT ID: NCT01046643
Last Updated: 2014-05-19
Results Overview
Measure the changes in brain activity in verbal tasks with hormone use (either estradiol or progesterone) versus placebo. The test is a deep and shallow verbal processing task, where the subjects are presented lists of words, one word at a time, and are asked to make one of 2 decisions about each list. One decision is whether each word is written in upper or lower case letters (shallow processing), and the other decision is whether each word denotes an abstract or concrete concept (deep processing). The test was administered 3 months after baseline and 38 weeks after baseline.
COMPLETED
NA
30 participants
August 2010 - March 2012
2014-05-19
Participant Flow
+++\_\_Women were recruited from 3/1/2010 to 7/29/2011 through local newspaper ads, flyers, electronic newsletters, bulletin boards, clinics and the Women's Health Registry, a University of Michigan database of women interested in participating in women's health related clinical research.
Several enrolled participants were excluded from the trial prior to assignment in groups on the basis of the risk factors identified at the pre-screening appointment. Some others did not qualify due to their lab results which did not meet the inclusion criteria.
Participant milestones
| Measure |
Estrogen Followed by Placebo
Estrogen treatment with Estradiol (E2)
One Estradiol capsule (1mg) once a day, at the same time each day, for 90 days followed by one Placebo capsule once per day for 90 days, at the same time each day
|
Progesterone Followed by Placebo
Progesterone (P10) treatment
One Progesterone (P10) (200 mg) capsule once a day, at the same time each day, for 90 days, followed by one Placebo capsule once per day for 90 days, at the same time each day.
|
Placebo Followed by Estrogen
One Placebo capsule once per day for 90 days, at the same time each day, followed by one Estradiol capsule (E2) (1mg) once a day, at the same time each day, for 90 days.
|
Placebo Followed by Progesterone
One Placebo capsule once per day for 90 days, at the same time each day, followed by one Progesterone (P10) (200 mg) capsule once a day, at the same time each day, for 90 days.
|
|---|---|---|---|---|
|
First Period Treatment or Placebo
STARTED
|
9
|
7
|
7
|
7
|
|
First Period Treatment or Placebo
COMPLETED
|
9
|
6
|
7
|
7
|
|
First Period Treatment or Placebo
NOT COMPLETED
|
0
|
1
|
0
|
0
|
|
Washout Period
STARTED
|
9
|
6
|
7
|
7
|
|
Washout Period
COMPLETED
|
9
|
6
|
7
|
7
|
|
Washout Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Second Period Treatment or Placebo
STARTED
|
9
|
6
|
7
|
7
|
|
Second Period Treatment or Placebo
COMPLETED
|
9
|
6
|
7
|
7
|
|
Second Period Treatment or Placebo
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Estrogen Followed by Placebo
Estrogen treatment with Estradiol (E2)
One Estradiol capsule (1mg) once a day, at the same time each day, for 90 days followed by one Placebo capsule once per day for 90 days, at the same time each day
|
Progesterone Followed by Placebo
Progesterone (P10) treatment
One Progesterone (P10) (200 mg) capsule once a day, at the same time each day, for 90 days, followed by one Placebo capsule once per day for 90 days, at the same time each day.
|
Placebo Followed by Estrogen
One Placebo capsule once per day for 90 days, at the same time each day, followed by one Estradiol capsule (E2) (1mg) once a day, at the same time each day, for 90 days.
|
Placebo Followed by Progesterone
One Placebo capsule once per day for 90 days, at the same time each day, followed by one Progesterone (P10) (200 mg) capsule once a day, at the same time each day, for 90 days.
|
|---|---|---|---|---|
|
First Period Treatment or Placebo
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Early Menopause Hormone Treatment and Cognition
Baseline characteristics by cohort
| Measure |
Estrogen and Placebo
n=16 Participants
Estrogen treatment with Estradiol (E2)
Participants received both an Estradiol capsule (E2) (1mg) and a Placebo capsule in a randomized sequence (for a total of two sequences of 90 days each, consisting of one capsule, once per day at the same time each day).
|
Progesterone and Placebo
n=14 Participants
Progesterone treatment (P10)
Participants received both a Progesterone capsule (P10) (200 mg) and a Placebo capsule in a randomized sequence (for a total of two sequences of 90 days each, consisting of one capsule, once per day at the same time each day).
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51.8 years
STANDARD_DEVIATION 2.2 • n=5 Participants
|
51.2 years
STANDARD_DEVIATION 2.9 • n=7 Participants
|
51.5 years
STANDARD_DEVIATION 2.5 • n=5 Participants
|
|
Gender
Female
|
9 participants
n=5 Participants
|
7 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Gender
Male
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=5 Participants
|
7 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Months since Last Menstrual Period
|
19.81 months
STANDARD_DEVIATION 9.57 • n=5 Participants
|
16.69 months
STANDARD_DEVIATION 9.80 • n=7 Participants
|
18.41 months
STANDARD_DEVIATION 9.63 • n=5 Participants
|
|
Education
|
15.75 years
STANDARD_DEVIATION 2.82 • n=5 Participants
|
17.19 years
STANDARD_DEVIATION 2.67 • n=7 Participants
|
16.4 years
STANDARD_DEVIATION 2.8 • n=5 Participants
|
|
Estradiol
|
17.75 pg/mL
STANDARD_DEVIATION 6.30 • n=5 Participants
|
14.38 pg/mL
STANDARD_DEVIATION 6.25 • n=7 Participants
|
16.24 pg/mL
STANDARD_DEVIATION 6.40 • n=5 Participants
|
|
Follicle-Stimulating Hormone
|
92.34 mIU/mL
STANDARD_DEVIATION 33.85 • n=5 Participants
|
80.86 mIU/mL
STANDARD_DEVIATION 21.60 • n=7 Participants
|
87.19 mIU/mL
STANDARD_DEVIATION 29.11 • n=5 Participants
|
|
BMI
|
27.13 kg/m²
STANDARD_DEVIATION 6.13 • n=5 Participants
|
28.38 kg/m²
STANDARD_DEVIATION 3.8 • n=7 Participants
|
27.69 kg/m²
STANDARD_DEVIATION 5.17 • n=5 Participants
|
PRIMARY outcome
Timeframe: August 2010 - March 2012Population: Within the Estrogen/Placebo groups, 3 participants were unable to complete the needed fMRI analyses due to adverse events, and in the Progesterone/Placebo groups, 1 participant's fMRI scans were damaged and unable to be used in the analysis.
Measure the changes in brain activity in verbal tasks with hormone use (either estradiol or progesterone) versus placebo. The test is a deep and shallow verbal processing task, where the subjects are presented lists of words, one word at a time, and are asked to make one of 2 decisions about each list. One decision is whether each word is written in upper or lower case letters (shallow processing), and the other decision is whether each word denotes an abstract or concrete concept (deep processing). The test was administered 3 months after baseline and 38 weeks after baseline.
Outcome measures
| Measure |
Estrogen
n=13 Participants
Estrogen treatment with Estradiol (E2)
Estradiol (E2) : One Estradiol capsule (1mg) once a day, at the same time each day, for 90 days
|
Progesterone
n=12 Participants
Progesterone treatment
Progesterone (P10) : One Progesterone (200 mg) capsule once a day, at the same time each day, for 90 days
|
Placebo (Estrogen)
n=13 Participants
Placebo phase of Estradiol (E2) treatment
One Placebo capsule once a day, at the same time each day, for 90 days
|
Placebo (Progesterone)
n=12 Participants
Placebo phase of Progesterone (P10) treatment
One Placebo capsule once a day, at the same time each day, for 90 days
|
|---|---|---|---|---|
|
Changes in Brain Activation Patterns in Verbal Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans
Medial Frontal Cortex
|
.14 percent BOLD signal changes
Standard Deviation .12
|
.13 percent BOLD signal changes
Standard Deviation .16
|
.05 percent BOLD signal changes
Standard Deviation 021
|
.13 percent BOLD signal changes
Standard Deviation .18
|
|
Changes in Brain Activation Patterns in Verbal Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans
Left Hippocampus
|
-.04 percent BOLD signal changes
Standard Deviation .14
|
-.01 percent BOLD signal changes
Standard Deviation .15
|
-.13 percent BOLD signal changes
Standard Deviation .16
|
.09 percent BOLD signal changes
Standard Deviation .34
|
|
Changes in Brain Activation Patterns in Verbal Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans
Right Hippocampus
|
-.06 percent BOLD signal changes
Standard Deviation .18
|
-.06 percent BOLD signal changes
Standard Deviation .13
|
-.14 percent BOLD signal changes
Standard Deviation .16
|
.01 percent BOLD signal changes
Standard Deviation .24
|
PRIMARY outcome
Timeframe: August 2010 - March 2012Population: Within the Estrogen/Placebo groups, 3 participants were unable to complete the needed fMRI analyses due to adverse events, and in the Progesterone/Placebo groups, 1 participant's fMRI scans were damaged.
Measure the changes in brain activity in visual tasks with hormone use (either estradiol or progesterone) versus placebo. The test is a visual working memory task, where the women are presented with 3 geometric grids on the screen. The target grid is on top, and 2 test grids are on the bottom. The women must decide if the right or left test grid matches the grid on top. There are 3 conditions: a match condition where all 3 grids are shown simultaneously, and 2 delay conditions, where the target grid is shown first, disappears, and the test grids appear after a 1 or a 4 second delay. The test was administered 3 months after baseline and 38 weeks after baseline.
Outcome measures
| Measure |
Estrogen
n=13 Participants
Estrogen treatment with Estradiol (E2)
Estradiol (E2) : One Estradiol capsule (1mg) once a day, at the same time each day, for 90 days
|
Progesterone
n=12 Participants
Progesterone treatment
Progesterone (P10) : One Progesterone (200 mg) capsule once a day, at the same time each day, for 90 days
|
Placebo (Estrogen)
n=13 Participants
Placebo phase of Estradiol (E2) treatment
One Placebo capsule once a day, at the same time each day, for 90 days
|
Placebo (Progesterone)
n=12 Participants
Placebo phase of Progesterone (P10) treatment
One Placebo capsule once a day, at the same time each day, for 90 days
|
|---|---|---|---|---|
|
Changes in Brain Activation Patterns in Visual Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans
Medial Frontal Cortex
|
.25 percent BOLD signal changes
Standard Deviation .17
|
.47 percent BOLD signal changes
Standard Deviation .28
|
.16 percent BOLD signal changes
Standard Deviation .41
|
.20 percent BOLD signal changes
Standard Deviation .43
|
|
Changes in Brain Activation Patterns in Visual Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans
Left Hippocampus
|
.21 percent BOLD signal changes
Standard Deviation .20
|
.38 percent BOLD signal changes
Standard Deviation .25
|
.23 percent BOLD signal changes
Standard Deviation .38
|
.21 percent BOLD signal changes
Standard Deviation .29
|
|
Changes in Brain Activation Patterns in Visual Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans
Right Hippocampus
|
.29 percent BOLD signal changes
Standard Deviation .17
|
.38 percent BOLD signal changes
Standard Deviation .29
|
.21 percent BOLD signal changes
Standard Deviation .48
|
.15 percent BOLD signal changes
Standard Deviation .29
|
SECONDARY outcome
Timeframe: August 2010 - March 2012Population: Within the Estrogen/Placebo groups, 3 participants were unable to complete the needed fMRI analyses due to adverse events, and in the Progesterone/Placebo groups, 1 participant's fMRI scans were damaged.
Changes in neuropsychological testing measures (verbal learning retention) with hormone use (either estradiol or progesterone) versus placebo. Subjects are given tests that present them with a series of words. They are asked to recall how many items they can remember, and then some time later, are asked to recall the items again. The retention measure is how many items they can remember at the later time point, compared to the earlier time point. Adapted from the Benton Visual Memory Test, Revised. The tests were administered 3 months after baseline and 38 weeks after baseline.
Outcome measures
| Measure |
Estrogen
n=13 Participants
Estrogen treatment with Estradiol (E2)
Estradiol (E2) : One Estradiol capsule (1mg) once a day, at the same time each day, for 90 days
|
Progesterone
n=12 Participants
Progesterone treatment
Progesterone (P10) : One Progesterone (200 mg) capsule once a day, at the same time each day, for 90 days
|
Placebo (Estrogen)
n=13 Participants
Placebo phase of Estradiol (E2) treatment
One Placebo capsule once a day, at the same time each day, for 90 days
|
Placebo (Progesterone)
n=12 Participants
Placebo phase of Progesterone (P10) treatment
One Placebo capsule once a day, at the same time each day, for 90 days
|
|---|---|---|---|---|
|
Neuropsychological Testing Scores - Verbal Learning Retention
|
96.79 percent retention
Standard Deviation 6.72
|
97.12 percent retention
Standard Deviation 15.30
|
94.94 percent retention
Standard Deviation 10.75
|
98.44 percent retention
Standard Deviation 12.25
|
SECONDARY outcome
Timeframe: August 2010 - March 2012Population: Within the Estrogen/Placebo groups, 3 participants were unable to complete the needed fMRI analyses due to adverse events, and in the Progesterone/Placebo groups, 1 participant's fMRI scans were damaged.
Changes in neuropsychological testing measures (visual learning retention) with hormone use (either estradiol or progesterone) versus placebo. Subjects are given tests that present them with a series of pictures. They are asked to recall how many items they can remember, and then some time later, are asked to recall the items again. The retention measure is how many items they can remember at the later time point, compared to the earlier time point. Adapted from the California Verbal Learning Test - 2nd edition. The tests were administered 3 months after baseline and 38 weeks after baseline.
Outcome measures
| Measure |
Estrogen
n=13 Participants
Estrogen treatment with Estradiol (E2)
Estradiol (E2) : One Estradiol capsule (1mg) once a day, at the same time each day, for 90 days
|
Progesterone
n=12 Participants
Progesterone treatment
Progesterone (P10) : One Progesterone (200 mg) capsule once a day, at the same time each day, for 90 days
|
Placebo (Estrogen)
n=13 Participants
Placebo phase of Estradiol (E2) treatment
One Placebo capsule once a day, at the same time each day, for 90 days
|
Placebo (Progesterone)
n=12 Participants
Placebo phase of Progesterone (P10) treatment
One Placebo capsule once a day, at the same time each day, for 90 days
|
|---|---|---|---|---|
|
Neuropsychological Testing Scores - Visual Learning Retention
|
93.31 percent retention
Standard Deviation 19.22
|
97.59 percent retention
Standard Deviation 13.67
|
97.01 percent retention
Standard Deviation 14.79
|
96.19 percent retention
Standard Deviation 12.06
|
Adverse Events
Estrogen Followed by Placebo
Progesterone Followed by Placebo
Placebo Followed by Estrogen
Placebo Followed by Progesterone
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Estrogen Followed by Placebo
n=9 participants at risk
Estrogen treatment with Estradiol (E2)
One Estradiol capsule (E2) (1mg) once a day, at the same time each day, for 90 days followed by one Placebo capsule once per day for 90 days, at the same time each day.
|
Progesterone Followed by Placebo
n=7 participants at risk
Progesterone treatment
One Progesterone (P10) (200 mg) capsule once a day, at the same time each day, for 90 days, followed by one Placebo capsule once per day for 90 days, at the same time each day.
|
Placebo Followed by Estrogen
n=7 participants at risk
One Placebo capsule once per day for 90 days, at the same time each day, followed by one Estradiol capsule (E2) (1mg) capsule once a day, at the same time each day, for 90 days.
|
Placebo Followed by Progesterone
n=7 participants at risk
One Placebo capsule once per day for 90 days, at the same time each day, followed by one Progesterone (P10) (200 mg) capsule once a day, at the same time each day, for 90 days.
|
|---|---|---|---|---|
|
General disorders
Claustrophobia
|
11.1%
1/9 • Number of events 1 • 2 years
|
0.00%
0/7 • 2 years
|
28.6%
2/7 • Number of events 2 • 2 years
|
0.00%
0/7 • 2 years
|
|
General disorders
Side effects of hormone use
|
0.00%
0/9 • 2 years
|
14.3%
1/7 • Number of events 1 • 2 years
|
14.3%
1/7 • Number of events 1 • 2 years
|
14.3%
1/7 • Number of events 1 • 2 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place