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The Effects of Aging and Estrogen on the Pituitary

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00386022
Recruitment Status : Unknown
Verified April 2017 by Janet E. Hall, MD, Massachusetts General Hospital.
Recruitment status was:  Active, not recruiting
First Posted : October 11, 2006
Results First Posted : April 13, 2017
Last Update Posted : April 13, 2017
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Janet E. Hall, MD, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Healthy
Interventions Drug: GnRH
Drug: NAL-GLU GnRH antagonist
Drug: Estrogen patch
Enrollment 19
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Younger PMW Older PMW
Hide Arm/Group Description

Postmenopausal women (PMW) 45-55 years old receiving the following series of treatments:

  1. A single subcutaneous injection of the NAL-GLU GnRH antagonist at a dose of 150 mcg/kg.
  2. GnRH doses of 25, 75, 250 and 750 ng/kg given IV every 4 hr

Participants studied at baseline (period 1) and after 1 month of transdermal estrogen 0.05 mg/day (period 2)

Postmenopausal women (PMW) 70-80 years old receiving the following series of treatments:

  1. A single subcutaneous injection of the NAL-GLU GnRH antagonist at a dose of 150 mcg/kg.
  2. GnRH doses of 25, 75, 250 and 750 ng/kg given IV every 4 hr

Participants studied at baseline (period 1) and after 1 month of transdermal estrogen 0.05 mg/day (period 2)

Period Title: Baseline
Started 10 9
All Doses of GnRH 10 9
Completed 10 9
Not Completed 0 0
Period Title: Plus Estrogen
Started 10 9
Estrogen Patch 8 9
All Doses GnRH 8 8
Completed 8 8
Not Completed 2 1
Reason Not Completed
Lost to Follow-up             2             0
Adverse Event             0             1
Arm/Group Title Younger PMW Older PMW Total
Hide Arm/Group Description

Postmenopausal women (PMW) 45-55 years old receiving the following series of treatments:

  1. A single subcutaneous injection of the NAL-GLU GnRH antagonist at a dose of 150 mcg/kg.
  2. GnRH doses of 25, 75, 250 and 750 ng/kg given IV every 4 hr

Participants studied at baseline (period 1) and after 1 month of transdermal estrogen 0.05 mg/day (period 2)

Postmenopausal women (PMW) 70-80 years old receiving the following series of treatments:

  1. A single subcutaneous injection of the NAL-GLU GnRH antagonist at a dose of 150 mcg/kg.
  2. GnRH doses of 25, 75, 250 and 750 ng/kg given IV every 4 hr

Participants studied at baseline (period 1) and after 1 month of transdermal estrogen 0.05 mg/day (period 2)

Total of all reporting groups
Overall Number of Baseline Participants 10 9 19
Hide Baseline Analysis Population Description
Healthy postmenopausal women who experienced their last menstrual period a minimum of 12 months previously and met all inclusion and exclusion criteria.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 9 participants 19 participants
52.9  (2.46) 72.8  (2.88) 61.9  (10.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 9 participants 19 participants
Female
10
 100.0%
9
 100.0%
19
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 9 participants 19 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
  30.0%
0
   0.0%
3
  15.8%
White
7
  70.0%
9
 100.0%
16
  84.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 9 participants 19 participants
10 9 19
1.Primary Outcome
Title Pituitary Response to GnRH
Hide Description Baseline LH and FSH responses to each of 4 GnRH doses - peak to nadir amplitude expressed as percent (%) change from nadir
Time Frame Peak hormone level within 2 hours post GnRH doses
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Younger PMW Older PMW
Hide Arm/Group Description:

Postmenopausal women aged 45-55 years studied at baseline using the following interventions:

  1. A single subcutaneous injection of the NAL-GLU GnRH antagonist at a dose of 150 mcg/kg.
  2. GnRH doses of 25, 75, 250 and 750 ng/kg given IV every 4 hr

Postmenopausal women aged 70-80 years studied at baseline using the following interventions:

  1. A single subcutaneous injection of the NAL-GLU GnRH antagonist at a dose of 150 mcg/kg.
  2. GnRH doses of 25, 75, 250 and 750 ng/kg given IV every 4 hr
Overall Number of Participants Analyzed 10 9
Mean (Standard Error)
Unit of Measure: Percent change
LH % change: 25 ng/kg GnRH 7.88  (1.76) 6.00  (1.49)
LH % change: 75 ng/kg GnRH 20.08  (2.94) 17.27  (3.65)
LH % change: 250 ng/kg GnRH 62.82  (12.15) 43.96  (5.70)
LH % change: 750 ng/kg GnRH 137.51  (14.17) 103.73  (8.60)
FSH % change 25 ng/kg GnRH 5.30  (.88) 4.32  (.89)
FSH % change: 75 ng/kg GnRH 8.01  (1.13) 6.98  (1.26)
FSH % change: 250 ng/kg GnRH 14.57  (1.87) 9.29  (1.32)
FSH % change: 750 ng/kg 23.55  (1.82) 17.53  (2.40)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Younger PMW, Older PMW
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments null hypothesis will be accepted if there is no difference in the LH response to GnRH as a function of dose in young or old postmenopausal women
Statistical Test of Hypothesis P-Value <0.001
Comments LH % change with dose
Method Repeated measures ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Younger PMW, Older PMW
Comments null hypothesis: there will be no difference in the LH and FSH responses to graded doses of GnRH between younger and older postmenopausal women
Type of Statistical Test Equivalence
Comments null hypothesis will be accepted if there is no difference in the LH response to GnRH between younger and older postmenopausal women
Statistical Test of Hypothesis P-Value <0.03
Comments LH % change with age
Method Repeated measures ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Younger PMW, Older PMW
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments null hypothesis will be accepted if there is no difference in the FSH response to GnRH as a function of dose in younger or older postmenopausal women
Statistical Test of Hypothesis P-Value <0.001
Comments FSH % change with dose
Method Repeated measures ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Younger PMW, Older PMW
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments null hypothesis will be accepted if there is no difference in the FSH response to GnRH between young and old postmenopausal women
Statistical Test of Hypothesis P-Value <0.005
Comments FSH % change with age
Method Repeated measures ANCOVA
Comments [Not Specified]
2.Primary Outcome
Title Effect of Estrogen on Pituitary Response to GnRH
Hide Description LH and FSH responses to each of 4 GnRH doses, expressed as change in amplitude [amp] from peak to nadir between plus estrogen and baseline conditions
Time Frame Peak hormone level within 2 hours post GnRH doses
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Young Postmenopausal Women Older Postmenopausal Women
Hide Arm/Group Description:

Postmenopausal women aged 45-55 years studied after 1 month of transdermal estrogen 0.05 mg/day using the following interventions:

  1. A single subcutaneous injection of the NAL-GLU GnRH antagonist at a dose of 150 mcg/kg.
  2. GnRH doses of 25, 75, 250 and 750 ng/kg given IV every 4 hr

Postmenopausal women aged 70-80 years studied after 1 month of transdermal estrogen 0.05 mg/day using the following interventions:

  1. A single subcutaneous injection of the NAL-GLU GnRH antagonist at a dose of 150 mcg/kg.
  2. GnRH doses of 25, 75, 250 and 750 ng/kg given IV every 4 hr
Overall Number of Participants Analyzed 8 8
Mean (Standard Error)
Unit of Measure: IU/L
LH amp change: 25 ng/kg GnRH -0.38  (1.9) -0.53  (1.0)
LH amp change: 75 ng/kg GnRH -2.9  (3.1) -0.54  (1.7)
LH amp change: 250 ng/kg GnRH -17.8  (8.0) -5.4  (3.4)
LH amp change: 750 ng/kg GnRH -27.1  (18.8) -14.2  (4.6)
FSH amp change: 25 ng/kg GnRH -2.7  (1.9) -0.6  (1.3)
FSH amp change: 75 ng/kg -6.7  (7.5) 0.21  (1.8)
FSH amp change: 250 ng/kg -12.1  (3.3) -1.9  (2.2)
FSH amp change: 750 ng/kg -15.4  (3.9) -5.8  (3.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Young Postmenopausal Women, Older Postmenopausal Women
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments null hypothesis will be accepted if there is no effect of estrogen on the LH response to GnRH in younger and older postmenopausal women
Statistical Test of Hypothesis P-Value <0.01
Comments LH amplitude response with estrogen
Method Repeated measured ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Young Postmenopausal Women, Older Postmenopausal Women
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments The null hypothesis will be accepted if there is no effect of estrogen on the FSH response to GnRH in younger and older postmenopausal women
Statistical Test of Hypothesis P-Value <0.0001
Comments FSH amplitude response with estrogen
Method Repeated measures ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Young Postmenopausal Women, Older Postmenopausal Women
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments The null hypothesis will be accepted if there is no effect of age on the effect of estrogen on the FSH response to GnRH
Statistical Test of Hypothesis P-Value <0.02
Comments FSH amplitude response to estrogen with age
Method Repeated measures ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Young Postmenopausal Women, Older Postmenopausal Women
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments The null hypothesis will be accepted if there is no effect of age on the effect of estrogen on the LH response to GnRH
Statistical Test of Hypothesis P-Value =0.4
Comments LH amplitude response to estrogen with age
Method Repeated measures ANCOVA
Comments [Not Specified]
Time Frame 3 months
Adverse Event Reporting Description Information on AEs was collected for a 3 month period from study entry for each subject.
 
Arm/Group Title Younger PMW Older PMW
Hide Arm/Group Description

Postmenopausal women aged 45-55 years studied at baseline (period 1) and after 1 month of transdermal estrogen 0.05 mg/day (period 2) using the following interventions:

  1. A single subcutaneous injection of the NAL-GLU GnRH antagonist at a dose of 150 mcg/kg.
  2. GnRH doses of 25, 75, 250 and 750 ng/kg given IV every 4 hr

Postmenopausal women aged 70-80 years studied at baseline (period 1) and after 1 month of transdermal estrogen 0.05 mg/day (period 2) using the following interventions:

  1. A single subcutaneous injection of the NAL-GLU GnRH antagonist at a dose of 150 mcg/kg.
  2. GnRH doses of 25, 75, 250 and 750 ng/kg given IV every 4 hr
All-Cause Mortality
Younger PMW Older PMW
Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)      0/9 (0.00%)    
Hide Serious Adverse Events
Younger PMW Older PMW
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      1/9 (11.11%)    
Cardiac disorders     
New Onset Rapid Atrial Fibrillation * [1]  0/10 (0.00%)  0 1/9 (11.11%)  1
*
Indicates events were collected by non-systematic assessment
[1]
On admission to Visit #2, subject's heart rate was 155 bpm. EKG revealed subject was in new onset rapid atrial fibrillation. Subject denied symptoms; transferred to a telemetry floor for rate control and discharged 2 days later. PCP notified.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Younger PMW Older PMW
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/10 (20.00%)      0/9 (0.00%)    
Infections and infestations     
genital herpes diagnosis * [1]  1/10 (10.00%)  1 0/9 (0.00%)  0
Musculoskeletal and connective tissue disorders     
fall * [2]  1/10 (10.00%)  1 0/9 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
diagnosis of genital herpes after baseline visit
[2]
Patient slipped on ice and twisted knee
No significant limitations were present in this study and the subsequent analysis.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Janet E. Hall
Organization: Massachusetts General Hospital
Phone: 617-877-1112
EMail: hall.janet@mgh.harvard.edu
Layout table for additonal information
Responsible Party: Janet E. Hall, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00386022    
Other Study ID Numbers: 2000-P-002498
R01AG013241 ( U.S. NIH Grant/Contract )
First Submitted: October 6, 2006
First Posted: October 11, 2006
Results First Submitted: May 22, 2014
Results First Posted: April 13, 2017
Last Update Posted: April 13, 2017