Trial Outcomes & Findings for Postmenopausal Women Estrogen and Progesterone Infusion (NCT NCT00455741)
NCT ID: NCT00455741
Last Updated: 2018-05-18
Results Overview
Difference between baseline LH (average of 3 samples drawn 15 min apart) and nadir LH based on a 3-point moving average of blood samples drawn every 4 hours over 120 hr, expressed as a percent of baseline (% baseline).
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
20 participants
Primary outcome timeframe
Baseline at 0 time before infusion, nadir occurred between 8 and 60 hr (mean 24 hr)
Results posted on
2018-05-18
Participant Flow
36 subjects consented; 6 failed screening, 2 decided not to participate.
1 subject terminated during study (hemoglobin drop) for a total of 24 completed.
Participant milestones
| Measure |
Younger PMW
Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
Older PMW
Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
12
|
|
Overall Study
COMPLETED
|
13
|
11
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Younger PMW
Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
Older PMW
Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
|---|---|---|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
Postmenopausal Women Estrogen and Progesterone Infusion
Baseline characteristics by cohort
| Measure |
Younger PMW
n=13 Participants
Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
Older PMW
n=12 Participants
Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
|
49.9 years
STANDARD_DEVIATION 3.8 • n=5 Participants
|
75.2 years
STANDARD_DEVIATION 3.6 • n=7 Participants
|
61.3 years
STANDARD_DEVIATION 13.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=5 Participants
|
12 participants
n=7 Participants
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline at 0 time before infusion, nadir occurred between 8 and 60 hr (mean 24 hr)Population: NOTE: 2 older and 2 younger postmenopausal women excluded from this analysis as estradiol levels exceeded physiological exposure levels
Difference between baseline LH (average of 3 samples drawn 15 min apart) and nadir LH based on a 3-point moving average of blood samples drawn every 4 hours over 120 hr, expressed as a percent of baseline (% baseline).
Outcome measures
| Measure |
Younger PMW
n=11 Participants
Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
Older PMW
n=9 Participants
Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
|---|---|---|
|
Effect of Aging on Estrogen Negative Feedback on LH
|
-52.8 % change from baseline
Standard Error 3.0
|
-53.2 % change from baseline
Standard Error 2.3
|
PRIMARY outcome
Timeframe: Onset of surge (average of 61 hr from beginnning of infusion until the end of the study (120 hr)Population: NOTE: 2 older and 2 younger postmenopausal women excluded from this analysis as estradiol levels exceeded physiological exposure levels
LH area under the curve in response to estrogen positive feedback. Area under the curve was calculated from blood samples drawn every 4 hours from the onset of positive feedback until the end of the study (120 min). The onset of positive feedback is defined as the time when LH first exceeds mean + 2SD of the previous three time points and shows a sustained rise.
Outcome measures
| Measure |
Younger PMW
n=11 Participants
Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
Older PMW
n=9 Participants
Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
|---|---|---|
|
Effect of Aging on Estrogen Positive Feedback on LH
|
4544.6 IU*hr/L
Standard Error 636.3
|
2885.5 IU*hr/L
Standard Error 316.7
|
SECONDARY outcome
Timeframe: Baseline vs 24 hr after the onset of steroid infusionPopulation: postmenopausal women
Regional cerebral glucose metabolism (rCMRglu) is used as a measure of neuronal metabolic activity and calculated as average uptake (voxels) of 18 flurodeoxyglucose within the region of interest (ROI) and expressed simply as units. Normalized uptake refers to co-registration of the PET with the MRI to provide more accurate anatomic correlates.
Outcome measures
| Measure |
Younger PMW
n=11 Participants
Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
Older PMW
n=11 Participants
Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
|---|---|---|
|
18 FDG Uptake at the Pituitary During Estrogen Infusion: LH Negative Feedback
|
45.8 units
Standard Error 4.5
|
48.4 units
Standard Error 4.0
|
SECONDARY outcome
Timeframe: 0 vs 24 hrPopulation: postmenopausal women
Regional cerebral glucose metabolism (rCMRglu) is used as a measure of neuronal metabolic activity and calculated as average uptake (voxels) of 18 flurodeoxyglucose within the region of interest (ROI) and expressed simply as units. Normalized uptake refers to co-registration of the PET with the MRI to provide more accurate anatomic correlates.
Outcome measures
| Measure |
Younger PMW
n=11 Participants
Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
Older PMW
n=11 Participants
Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
|---|---|---|
|
18 FDG Uptake at the Hypothalamus During Estrogen Infusion: LH Negative Feedback
|
69.0 units
Standard Error 3.3
|
63.1 units
Standard Error 2.8
|
SECONDARY outcome
Timeframe: 24 hr vs 72 hrPopulation: postmenopausal women
Regional cerebral glucose metabolism (rCMRglu) is used as a measure of neuronal metabolic activity and calculated as average uptake (voxels) of 18 flurodeoxyglucose within the region of interest (ROI) and expressed simply as units. Normalized uptake refers to co-registration of the PET with the MRI to provide more accurate anatomic correlates.
Outcome measures
| Measure |
Younger PMW
n=11 Participants
Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
Older PMW
n=11 Participants
Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
|---|---|---|
|
18 FDG Uptake at the Pituitary During Estrogen Infusion: LH Positive Feedback
|
48.0 units
Standard Error 4.0
|
54.3 units
Standard Error 4.4
|
SECONDARY outcome
Timeframe: 24 vs 72 hrPopulation: postmenopausal women
Regional cerebral glucose metabolism (rCMRglu) is used as a measure of neuronal metabolic activity and calculated as average uptake (voxels) of 18 flurodeoxyglucose within the region of interest (ROI) and expressed simply as units. Normalized uptake refers to co-registration of the PET with the MRI to provide more accurate anatomic correlates.
Outcome measures
| Measure |
Younger PMW
n=11 Participants
Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
Older PMW
n=11 Participants
Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
|---|---|---|
|
18 FDG Uptake at the Hypothalamus During Estrogen Infusion: LH Positive Feedback
|
63.1 unit
Standard Error 2.8
|
66.2 unit
Standard Error 3.7
|
Adverse Events
Younger PMW
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Older PMW
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Younger PMW
n=13 participants at risk
Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
Older PMW
n=12 participants at risk
Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions.
Estradiol infusion:
Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr.
Progesterone infusion:
Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
|
|---|---|---|
|
Blood and lymphatic system disorders
anemia
|
0.00%
0/13 • 60 days for each subject; 4 years in total
As in clinicaltrials.gov
|
8.3%
1/12 • Number of events 1 • 60 days for each subject; 4 years in total
As in clinicaltrials.gov
|
|
Vascular disorders
vasomotor symptoms
|
15.4%
2/13 • Number of events 2 • 60 days for each subject; 4 years in total
As in clinicaltrials.gov
|
0.00%
0/12 • 60 days for each subject; 4 years in total
As in clinicaltrials.gov
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place