Trial Outcomes & Findings for Timing Estrogen After MenoPaUSe (NCT NCT01605071)
NCT ID: NCT01605071
Last Updated: 2021-03-01
Results Overview
Estrogen mediated change in glucose disposal rate and time since menopause * Baseline GDR (no difference between groups) * E2 mediated change (significant difference between groups) randomized order of testing, cross-over design
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
53 participants
Primary outcome timeframe
after 1wk estradiol or placebo
Results posted on
2021-03-01
Participant Flow
Participant milestones
| Measure |
Early Postmenopausal
Postmenopausal women within 6 years of last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
Late Postmenopausal
Postmenopausal women more than 10 years since last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
|---|---|---|
|
Overall Study
STARTED
|
27
|
26
|
|
Overall Study
COMPLETED
|
24
|
24
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
| Measure |
Early Postmenopausal
Postmenopausal women within 6 years of last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
Late Postmenopausal
Postmenopausal women more than 10 years since last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
2
|
Baseline Characteristics
Timing Estrogen After MenoPaUSe
Baseline characteristics by cohort
| Measure |
Early Postmenopausal
n=22 Participants
Postmenopausal women within 6 years of last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
Late Postmenopausal
n=24 Participants
Postmenopausal women more than 10 years since last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
Total
n=46 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
45-70 years of age
|
22 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Female
|
22 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
22 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: after 1wk estradiol or placeboEstrogen mediated change in glucose disposal rate and time since menopause * Baseline GDR (no difference between groups) * E2 mediated change (significant difference between groups) randomized order of testing, cross-over design
Outcome measures
| Measure |
Early Postmenopausal
n=22 Participants
Postmenopausal women within 6 years of last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
Late Postmenopausal
n=24 Participants
Postmenopausal women more than 10 years since last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
|---|---|---|
|
Insulin-mediated Glucose Disposal Rate (Hyperinsulinemic-euglycemic Clamp)
Placebo
|
11.7 mg/kg FFM/min
Standard Deviation 2.8
|
11.5 mg/kg FFM/min
Standard Deviation 3.0
|
|
Insulin-mediated Glucose Disposal Rate (Hyperinsulinemic-euglycemic Clamp)
Estrogen
|
12.2 mg/kg FFM/min
Standard Deviation 3.1
|
10.7 mg/kg FFM/min
Standard Deviation 2.9
|
SECONDARY outcome
Timeframe: after 1wk estradiol or placeboEstrogen receptors (ERα and ERβ) differences in time since menopause and estrogen treatment randomized order of testing, cross-over design
Outcome measures
| Measure |
Early Postmenopausal
n=13 Participants
Postmenopausal women within 6 years of last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
Late Postmenopausal
n=14 Participants
Postmenopausal women more than 10 years since last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
|---|---|---|
|
Skeletal Muscle Estrogen Receptor Expression
ERβ cytosolic protein (Estrogen)
|
0.89 AU
Standard Deviation 0.44
|
0.64 AU
Standard Deviation 0.25
|
|
Skeletal Muscle Estrogen Receptor Expression
ERα nuclear protein (Placebo)
|
1 AU
Standard Deviation 0.25
|
0.71 AU
Standard Deviation 0.20
|
|
Skeletal Muscle Estrogen Receptor Expression
ERα nuclear protein (Estrogen)
|
0.92 AU
Standard Deviation 0.37
|
0.80 AU
Standard Deviation 0.31
|
|
Skeletal Muscle Estrogen Receptor Expression
ERβ nuclear protein (Placebo)
|
1 AU
Standard Deviation 0.35
|
0.78 AU
Standard Deviation 0.26
|
|
Skeletal Muscle Estrogen Receptor Expression
ERβ nuclear protein (Estrogen)
|
0.97 AU
Standard Deviation 0.47
|
0.75 AU
Standard Deviation 0.26
|
|
Skeletal Muscle Estrogen Receptor Expression
ERα cytosolic protein (Placebo)
|
1 AU
Standard Deviation 0.40
|
1 AU
Standard Deviation 0.62
|
|
Skeletal Muscle Estrogen Receptor Expression
ERα cytosolic protein (Estrogen)
|
0.63 AU
Standard Deviation 0.32
|
0.83 AU
Standard Deviation 0.45
|
|
Skeletal Muscle Estrogen Receptor Expression
ERβ cytosolic protein (Placebo)
|
1 AU
Standard Deviation 0.41
|
0.7 AU
Standard Deviation 0.26
|
SECONDARY outcome
Timeframe: after 1wk estradiol or placeboEstrogen receptors (ERα and ERβ) differences in time since menopause and estrogen treatment randomized order of testing, cross-over design
Outcome measures
| Measure |
Early Postmenopausal
n=13 Participants
Postmenopausal women within 6 years of last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
Late Postmenopausal
n=14 Participants
Postmenopausal women more than 10 years since last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
|---|---|---|
|
Skeletal Muscle Estrogen Receptor Expression (Protein/Cyto Protein)
ERα nuclear protein/cyto protein (Placebo)
|
0.94 ratio
Standard Deviation 0.34
|
0.78 ratio
Standard Deviation 0.37
|
|
Skeletal Muscle Estrogen Receptor Expression (Protein/Cyto Protein)
ERα nuclear protein/cyto protein (Estrogen)
|
1.49 ratio
Standard Deviation 0.92
|
0.98 ratio
Standard Deviation 0.39
|
|
Skeletal Muscle Estrogen Receptor Expression (Protein/Cyto Protein)
ERβ nuclear protein/cyto protein (Placebo)
|
1 ratio
Standard Deviation 0.53
|
1.13 ratio
Standard Deviation 0.52
|
|
Skeletal Muscle Estrogen Receptor Expression (Protein/Cyto Protein)
ERβ nuclear protein/cyto protein (Estrogen)
|
1.13 ratio
Standard Deviation 0.54
|
1.07 ratio
Standard Deviation 0.39
|
SECONDARY outcome
Timeframe: BaselineAdipose tissue estrogen receptor expression associated with age and menopause Abdominal and femoral subcutaneous adipose tissue ERα and ERβ expression
Outcome measures
| Measure |
Early Postmenopausal
n=23 Participants
Postmenopausal women within 6 years of last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
Late Postmenopausal
n=22 Participants
Postmenopausal women more than 10 years since last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
|---|---|---|
|
Adipose Tissue Estrogen Receptor Expression
Abdominal ERα (ESR1)
|
1.58 2ΔCT
Standard Deviation 1.17
|
0.96 2ΔCT
Standard Deviation 0.58
|
|
Adipose Tissue Estrogen Receptor Expression
Abdominal ERβ (ESR2)
|
1.17 2ΔCT
Standard Deviation 0.70
|
1.22 2ΔCT
Standard Deviation 0.64
|
|
Adipose Tissue Estrogen Receptor Expression
Femoral ERα (ESR1)
|
1.44 2ΔCT
Standard Deviation 0.98
|
0.97 2ΔCT
Standard Deviation 0.49
|
|
Adipose Tissue Estrogen Receptor Expression
Femoral ERβ (ESR2)
|
1.09 2ΔCT
Standard Deviation 0.68
|
1.25 2ΔCT
Standard Deviation 0.71
|
SECONDARY outcome
Timeframe: BaselineAdipose tissue estrogen receptor expression associated with age and menopause Abdominal and femoral subcutaneous adipose tissue ratio of ERα:ERβ expression
Outcome measures
| Measure |
Early Postmenopausal
n=23 Participants
Postmenopausal women within 6 years of last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
Late Postmenopausal
n=22 Participants
Postmenopausal women more than 10 years since last menses who never used estrogen-based hormone therapy
Estradiol: 1 week of transdermal estradiol (0.15mg)
1 week of transdermal placebo
|
|---|---|---|
|
Adipose Tissue Estrogen Receptor Expression (ERα:ERβ)
Abdominal ERα:ERβ (ESR1:ESR2)
|
1.47 ratio
Standard Deviation 0.71
|
0.89 ratio
Standard Deviation 0.55
|
|
Adipose Tissue Estrogen Receptor Expression (ERα:ERβ)
Femoral ERα:ERβ (ESR1:ESR2)
|
1.143 ratio
Standard Deviation 0.85
|
0.87 ratio
Standard Deviation 0.37
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Estrogen
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=37 participants at risk
1 week of transdermal placebo
|
Estrogen
n=37 participants at risk
Estradiol: 1 week of transdermal estradiol (0.15mg)
|
|---|---|---|
|
General disorders
Migraine/nausea
|
5.4%
2/37 • Number of events 2 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
0.00%
0/37 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
|
Skin and subcutaneous tissue disorders
bruising/discomfort
|
2.7%
1/37 • Number of events 1 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
0.00%
0/37 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
|
Respiratory, thoracic and mediastinal disorders
CT scan abnormality
|
2.7%
1/37 • Number of events 1 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
0.00%
0/37 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
|
General disorders
Irritation at IV site
|
2.7%
1/37 • Number of events 1 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
0.00%
0/37 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
|
General disorders
Extended E2 administration
|
0.00%
0/37 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
2.7%
1/37 • Number of events 1 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
|
General disorders
Low pulse
|
2.7%
1/37 • Number of events 1 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
0.00%
0/37 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
|
Skin and subcutaneous tissue disorders
IV infiltration
|
0.00%
0/37 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
2.7%
1/37 • Number of events 1 • 4 months participants were randomized in a crossover manner, visits were separated by approximately 2 months. - 1 week of placebo/study testing - 1 week of transdermal E2/study testing.
No deaths or serious adverse events occurred in this study
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place