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Fat Mediated Modulation of Reproductive and Endocrine Function in Young Athletes

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: NCT00946192
Recruitment Status : Active, not recruiting
First Posted : July 24, 2009
Results First Posted : March 18, 2020
Last Update Posted : June 11, 2020
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Madhusmita Misra, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Exercise-related Amenorrhea
Interventions Drug: Transdermal 17Beta-estradiol, progesterone
Drug: Ethinyl Estradiol + Desogestrel
Dietary Supplement: Sham Comparator
Enrollment 121
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Estrogen Patch Estrogen Pill Control
Hide Arm/Group Description

17Beta-estradiol transdermal patch twice weekly application for 12 months

Transdermal 17Beta-estradiol, progesterone: 100 mcg/day 17Beta-estradiol; transdermal twice weekly application for 12 months (with cyclic micronized progesterone pills (Prometrium): 200 mg taken orally daily Day 1 to Day 12 each month) + Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

One pill containing estrogen and progesterone taken daily for 21 days followed by placebo pills only for 7 days; regimen repeated for 12 months.

Ethinyl Estradiol + Desogestrel: Oral ethinyl estradiol (0.03 mg) + desogestrel (0.15 mg) + Elemental calcium 1200 mg and Vit D 400 IU taken once daily

Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

Sham Comparator: Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

Period Title: Overall Study
Started 43 40 38
Completed 25 22 26
Not Completed 18 18 12
Reason Not Completed
Lost to Follow-up             6             11             9
Withdrawal by Subject             10             7             3
Did not start medication             2             0             0
Arm/Group Title Estrogen Patch Estrogen Pill Control Total
Hide Arm/Group Description

17Beta-estradiol transdermal patch twice weekly application for 12 months

Transdermal 17Beta-estradiol, progesterone: 100 mcg/day 17Beta-estradiol; transdermal twice weekly application for 12 months (with cyclic micronized progesterone pills (Prometrium): 200 mg taken orally daily Day 1 to Day 12 each month) + Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

One pill containing estrogen and progesterone taken daily for 21 days followed by placebo pills only for 7 days; regimen repeated for 12 months.

Ethinyl Estradiol + Desogestrel: Oral ethinyl estradiol (0.03 mg) + desogestrel (0.15 mg) + Elemental calcium 1200 mg and Vit D 400 IU taken once daily

Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

Sham Comparator: Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

Total of all reporting groups
Overall Number of Baseline Participants 43 40 38 121
Hide Baseline Analysis Population Description
Athletes with amenorrhea
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 43 participants 40 participants 38 participants 121 participants
19.86  (0.40) 20.30  (0.44) 19.35  (0.38) 19.84  (0.41)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants 40 participants 38 participants 121 participants
Female
43
 100.0%
40
 100.0%
38
 100.0%
121
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants 40 participants 38 participants 121 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
2
   5.3%
2
   1.7%
Not Hispanic or Latino
43
 100.0%
40
 100.0%
36
  94.7%
119
  98.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants 40 participants 38 participants 121 participants
American Indian or Alaska Native
1
   2.3%
0
   0.0%
0
   0.0%
1
   0.8%
Asian
4
   9.3%
0
   0.0%
1
   2.6%
5
   4.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
37
  86.0%
38
  95.0%
35
  92.1%
110
  90.9%
More than one race
1
   2.3%
2
   5.0%
2
   5.3%
5
   4.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 43 participants 40 participants 38 participants 121 participants
43 40 38 121
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 43 participants 40 participants 38 participants 121 participants
20.45  (0.35) 20.80  (0.39) 20.75  (0.34) 20.67  (0.36)
1.Primary Outcome
Title Change in Lumbar Bone Mineral Density
Hide Description Change in bone density with transdermal estrogen versus oral estrogen or no estrogen in amenorrheic athletes
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Estrogen Patch Estrogen Pill Control
Hide Arm/Group Description:

17Beta-estradiol transdermal patch twice weekly application for 12 months

Transdermal 17Beta-estradiol, progesterone: 100 mcg/day 17Beta-estradiol; transdermal twice weekly application for 12 months (with cyclic micronized progesterone pills (Prometrium): 200 mg taken orally daily Day 1 to Day 12 each month) + Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

One pill containing estrogen and progesterone taken daily for 21 days followed by placebo pills only for 7 days; regimen repeated for 12 months.

Ethinyl Estradiol + Desogestrel: Oral ethinyl estradiol (0.03 mg) + desogestrel (0.15 mg) + Elemental calcium 1200 mg and Vit D 400 IU taken once daily

Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

Sham Comparator: Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

Overall Number of Participants Analyzed 25 22 26
Mean (Standard Error)
Unit of Measure: g/cm^2
0.025  (0.011) 0.008  (0.011) 0.012  (0.012)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estrogen Patch, Estrogen Pill, Control
Comments [Not Specified]
Type of Statistical Test Other
Comments Least square means
Statistical Test of Hypothesis P-Value 0.039
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
2.Secondary Outcome
Title Change in Total Volumetric Bone Mineral Density (Tibia)
Hide Description Change in total volumetric bone density at the tibia with transdermal estrogen versus oral estrogen or no estrogen in amenorrheic athletes
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Estrogen Patch Estrogen Pill Control
Hide Arm/Group Description:

17Beta-estradiol transdermal patch twice weekly application for 12 months

Transdermal 17Beta-estradiol, progesterone: 100 mcg/day 17Beta-estradiol; transdermal twice weekly application for 12 months (with cyclic micronized progesterone pills (Prometrium): 200 mg taken orally daily Day 1 to Day 12 each month) + Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

One pill containing estrogen and progesterone taken daily for 21 days followed by placebo pills only for 7 days; regimen repeated for 12 months.

Ethinyl Estradiol + Desogestrel: Oral ethinyl estradiol (0.03 mg) + desogestrel (0.15 mg) + Elemental calcium 1200 mg and Vit D 400 IU taken once daily

Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

Sham Comparator: Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

Overall Number of Participants Analyzed 24 24 27
Mean (Standard Error)
Unit of Measure: mg HA/cm^3
7.01  (3.06) 1.17  (3.05) 3.71  (4.44)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estrogen Patch, Estrogen Pill, Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Time Frame 1 year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Estrogen Patch Estrogen Pill Control
Hide Arm/Group Description

17Beta-estradiol transdermal patch twice weekly application for 12 months

Transdermal 17Beta-estradiol, progesterone: 100 mcg/day 17Beta-estradiol; transdermal twice weekly application for 12 months (with cyclic micronized progesterone pills (Prometrium): 200 mg taken orally daily Day 1 to Day 12 each month) + Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

One pill containing estrogen and progesterone taken daily for 21 days followed by placebo pills only for 7 days; regimen repeated for 12 months.

Ethinyl Estradiol + Desogestrel: Oral ethinyl estradiol (0.03 mg) + desogestrel (0.15 mg) + Elemental calcium 1200 mg and Vit D 400 IU taken once daily

Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

Sham Comparator: Elemental calcium 1200 mg and Vit D 400 IU taken orally daily

All-Cause Mortality
Estrogen Patch Estrogen Pill Control
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/43 (0.00%)      0/40 (0.00%)      0/38 (0.00%)    
Hide Serious Adverse Events
Estrogen Patch Estrogen Pill Control
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/43 (6.98%)      0/40 (0.00%)      1/38 (2.63%)    
Endocrine disorders       
Fractures or sprains   3/43 (6.98%)  3 0/40 (0.00%)  0 0/38 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Sinus surgery   0/43 (0.00%)  0 0/40 (0.00%)  1/38 (2.63%)  1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0.1%
Estrogen Patch Estrogen Pill Control
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/43 (23.26%)      13/40 (32.50%)      1/38 (2.63%)    
Endocrine disorders       
Breast tenderness   1/43 (2.33%)  1 1/40 (2.50%)  1 0/38 (0.00%)  0
Early menses   0/43 (0.00%)  0 1/40 (2.50%)  1 0/38 (0.00%)  0
Gastrointestinal disorders       
Nausea   0/43 (0.00%)  0 2/40 (5.00%)  2 0/38 (0.00%)  0
Gastritis   1/43 (2.33%)  1 0/40 (0.00%)  0 0/38 (0.00%)  0
Diarrhea   1/43 (2.33%)  1 0/40 (0.00%)  0 0/38 (0.00%)  0
General disorders       
Fatigue   0/43 (0.00%)  0 1/40 (2.50%)  1 0/38 (0.00%)  0
Bloating   2/43 (4.65%)  2 0/40 (0.00%)  0 0/38 (0.00%)  0
Generalized discomfort   1/43 (2.33%)  1 0/40 (0.00%)  0 0/38 (0.00%)  0
Infections and infestations       
Yeast infection   0/43 (0.00%)  0 1/40 (2.50%)  1 0/38 (0.00%)  0
Mononucleosis   0/43 (0.00%)  0 1/40 (2.50%)  1 0/38 (0.00%)  0
Investigations       
Electrolyte changes   0/43 (0.00%)  0 1/40 (2.50%)  1 0/38 (0.00%)  0
Metabolism and nutrition disorders       
Fluid retention   0/43 (0.00%)  0 1/40 (2.50%)  1 0/38 (0.00%)  0
Nervous system disorders       
Headache   2/43 (4.65%)  2 1/40 (2.50%)  1 0/38 (0.00%)  0
Product Issues       
Mood swings   0/43 (0.00%)  0 1/40 (2.50%)  1 0/38 (0.00%)  0
Psychiatric disorders       
Worsening depression   1/43 (2.33%)  1 1/40 (2.50%)  1 0/38 (0.00%)  0
Reproductive system and breast disorders       
Decreased libido   0/43 (0.00%)  0 1/40 (2.50%)  1 0/38 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Upper respiratory symptoms   0/43 (0.00%)  0 0/40 (0.00%)  0 1/38 (2.63%)  1
Skin and subcutaneous tissue disorders       
Skin rash   1/43 (2.33%)  1 0/40 (0.00%)  0 0/38 (0.00%)  0
Skin tags   0/43 (0.00%)  0 1/40 (2.50%)  1 0/38 (0.00%)  0
Vascular disorders       
Dizziness   1/43 (2.33%)  1 0/40 (0.00%)  0 0/38 (0.00%)  0
Vasovagal response   0/43 (0.00%)  0 2/40 (5.00%)  2 0/38 (0.00%)  0
Indicates events were collected by systematic assessment
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: Madhu Misra, MD; Chief, Pediatric Endocrine
Organization: Massachusetts General Hospital and Harvard Medical School
Phone: 6177245602
EMail: mmisra@mgh.harvard.edu
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Madhusmita Misra, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00946192    
Other Study ID Numbers: 2009P000353
R01HD060827-01A1 ( U.S. NIH Grant/Contract )
First Submitted: July 22, 2009
First Posted: July 24, 2009
Results First Submitted: February 15, 2020
Results First Posted: March 18, 2020
Last Update Posted: June 11, 2020