Trial Outcomes & Findings for Fat Mediated Modulation of Reproductive and Endocrine Function in Young Athletes (NCT NCT00946192)
NCT ID: NCT00946192
Last Updated: 2021-06-11
Results Overview
Change in bone density with transdermal estrogen versus oral estrogen or no estrogen in amenorrheic athletes
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
121 participants
Primary outcome timeframe
12 months
Results posted on
2021-06-11
Participant Flow
Participant milestones
| Measure |
Estrogen Patch
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
|
Estrogen Pill
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
|
Control
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 Study
STARTED
|
43
|
40
|
38
|
|
Overall Study
COMPLETED
|
25
|
22
|
26
|
|
Overall Study
NOT COMPLETED
|
18
|
18
|
12
|
Reasons for withdrawal
| Measure |
Estrogen Patch
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
|
Estrogen Pill
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
|
Control
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 Study
Lost to Follow-up
|
6
|
11
|
9
|
|
Overall Study
Withdrawal by Subject
|
10
|
7
|
3
|
|
Overall Study
Did not start medication
|
2
|
0
|
0
|
Baseline Characteristics
Fat Mediated Modulation of Reproductive and Endocrine Function in Young Athletes
Baseline characteristics by cohort
| Measure |
Estrogen Patch
n=43 Participants
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
|
Estrogen Pill
n=40 Participants
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
|
Control
n=38 Participants
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
n=121 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
19.86 years
STANDARD_DEVIATION 0.40 • n=5 Participants
|
20.30 years
STANDARD_DEVIATION 0.44 • n=7 Participants
|
19.35 years
STANDARD_DEVIATION 0.38 • n=5 Participants
|
19.84 years
STANDARD_DEVIATION 0.41 • n=4 Participants
|
|
Sex: Female, Male
Female
|
43 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
121 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
43 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
119 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
5 Participants
n=4 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
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
37 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
110 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
43 participants
n=5 Participants
|
40 participants
n=7 Participants
|
38 participants
n=5 Participants
|
121 participants
n=4 Participants
|
|
BMI
|
20.45 kg/m^2
STANDARD_DEVIATION 0.35 • n=5 Participants
|
20.80 kg/m^2
STANDARD_DEVIATION 0.39 • n=7 Participants
|
20.75 kg/m^2
STANDARD_DEVIATION 0.34 • n=5 Participants
|
20.67 kg/m^2
STANDARD_DEVIATION 0.36 • n=4 Participants
|
PRIMARY outcome
Timeframe: 12 monthsChange in bone density with transdermal estrogen versus oral estrogen or no estrogen in amenorrheic athletes
Outcome measures
| Measure |
Estrogen Patch
n=25 Participants
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
|
Estrogen Pill
n=22 Participants
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
|
Control
n=26 Participants
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
|
|---|---|---|---|
|
Change in Lumbar Bone Mineral Density
|
0.025 g/cm^2
Standard Error 0.011
|
0.008 g/cm^2
Standard Error 0.011
|
0.012 g/cm^2
Standard Error 0.012
|
SECONDARY outcome
Timeframe: 12 monthsChange in total volumetric bone density at the tibia with transdermal estrogen versus oral estrogen or no estrogen in amenorrheic athletes
Outcome measures
| Measure |
Estrogen Patch
n=24 Participants
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
|
Estrogen Pill
n=24 Participants
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
|
Control
n=27 Participants
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
|
|---|---|---|---|
|
Change in Total Volumetric Bone Mineral Density (Tibia)
|
7.01 mg HA/cm^3
Standard Error 3.06
|
1.17 mg HA/cm^3
Standard Error 3.05
|
3.71 mg HA/cm^3
Standard Error 4.44
|
Adverse Events
Estrogen Patch
Serious events: 3 serious events
Other events: 10 other events
Deaths: 0 deaths
Estrogen Pill
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Control
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Estrogen Patch
n=43 participants at risk
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
|
Estrogen Pill
n=40 participants at risk
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
|
Control
n=38 participants at risk
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
|
|---|---|---|---|
|
Endocrine disorders
Fractures or sprains
|
7.0%
3/43 • Number of events 3 • 1 year
|
0.00%
0/40 • 1 year
|
0.00%
0/38 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Sinus surgery
|
0.00%
0/43 • 1 year
|
0.00%
0/40 • 1 year
|
2.6%
1/38 • Number of events 1 • 1 year
|
Other adverse events
| Measure |
Estrogen Patch
n=43 participants at risk
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
|
Estrogen Pill
n=40 participants at risk
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
|
Control
n=38 participants at risk
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
|
|---|---|---|---|
|
Infections and infestations
Mononucleosis
|
0.00%
0/43 • 1 year
|
2.5%
1/40 • Number of events 1 • 1 year
|
0.00%
0/38 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory symptoms
|
0.00%
0/43 • 1 year
|
0.00%
0/40 • 1 year
|
2.6%
1/38 • Number of events 1 • 1 year
|
|
Skin and subcutaneous tissue disorders
Skin tags
|
0.00%
0/43 • 1 year
|
2.5%
1/40 • Number of events 1 • 1 year
|
0.00%
0/38 • 1 year
|
|
Investigations
Electrolyte changes
|
0.00%
0/43 • 1 year
|
2.5%
1/40 • Number of events 1 • 1 year
|
0.00%
0/38 • 1 year
|
|
Nervous system disorders
Headache
|
4.7%
2/43 • Number of events 2 • 1 year
|
2.5%
1/40 • Number of events 1 • 1 year
|
0.00%
0/38 • 1 year
|
|
Vascular disorders
Dizziness
|
2.3%
1/43 • Number of events 1 • 1 year
|
0.00%
0/40 • 1 year
|
0.00%
0/38 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/43 • 1 year
|
5.0%
2/40 • Number of events 2 • 1 year
|
0.00%
0/38 • 1 year
|
|
General disorders
Fatigue
|
0.00%
0/43 • 1 year
|
2.5%
1/40 • Number of events 1 • 1 year
|
0.00%
0/38 • 1 year
|
|
Endocrine disorders
Breast tenderness
|
2.3%
1/43 • Number of events 1 • 1 year
|
2.5%
1/40 • Number of events 1 • 1 year
|
0.00%
0/38 • 1 year
|
|
Metabolism and nutrition disorders
Fluid retention
|
0.00%
0/43 • 1 year
|
2.5%
1/40 • Number of events 1 • 1 year
|
0.00%
0/38 • 1 year
|
|
General disorders
Bloating
|
4.7%
2/43 • Number of events 2 • 1 year
|
0.00%
0/40 • 1 year
|
0.00%
0/38 • 1 year
|
|
Endocrine disorders
Early menses
|
0.00%
0/43 • 1 year
|
2.5%
1/40 • Number of events 1 • 1 year
|
0.00%
0/38 • 1 year
|
|
Infections and infestations
Yeast infection
|
0.00%
0/43 • 1 year
|
2.5%
1/40 • Number of events 1 • 1 year
|
0.00%
0/38 • 1 year
|
|
Psychiatric disorders
Worsening depression
|
2.3%
1/43 • Number of events 1 • 1 year
|
2.5%
1/40 • Number of events 1 • 1 year
|
0.00%
0/38 • 1 year
|
|
Product Issues
Mood swings
|
0.00%
0/43 • 1 year
|
2.5%
1/40 • Number of events 1 • 1 year
|
0.00%
0/38 • 1 year
|
|
General disorders
Generalized discomfort
|
2.3%
1/43 • Number of events 1 • 1 year
|
0.00%
0/40 • 1 year
|
0.00%
0/38 • 1 year
|
|
Vascular disorders
Vasovagal response
|
0.00%
0/43 • 1 year
|
5.0%
2/40 • Number of events 2 • 1 year
|
0.00%
0/38 • 1 year
|
|
Skin and subcutaneous tissue disorders
Skin rash
|
2.3%
1/43 • Number of events 1 • 1 year
|
0.00%
0/40 • 1 year
|
0.00%
0/38 • 1 year
|
|
Gastrointestinal disorders
Gastritis
|
2.3%
1/43 • Number of events 1 • 1 year
|
0.00%
0/40 • 1 year
|
0.00%
0/38 • 1 year
|
|
Reproductive system and breast disorders
Decreased libido
|
0.00%
0/43 • 1 year
|
2.5%
1/40 • Number of events 1 • 1 year
|
0.00%
0/38 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
2.3%
1/43 • Number of events 1 • 1 year
|
0.00%
0/40 • 1 year
|
0.00%
0/38 • 1 year
|
Additional Information
Madhu Misra, MD; Chief, Pediatric Endocrine
Massachusetts General Hospital and Harvard Medical School
Phone: 6177245602
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place