Trial Outcomes & Findings for Bioidentical 'Natural' Hormone Evaluation in Early Menopause (NCT NCT00302731)
NCT ID: NCT00302731
Last Updated: 2018-07-06
Results Overview
To determine if bioidentical hormone replacement therapy is associated with change in lipid profiles (surrogate marker for cardiovascular disease) when compared to Prempro and provide safety data to proceed to larger trial. This was determined by evaluating lipid levels at baseline and during the 12-month treatment period. Participants' values were averaged at baseline and again at 12 months; the average of the baseline value was subtracted from the average at completion.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
21 participants
Primary outcome timeframe
Baseline and month 12
Results posted on
2018-07-06
Participant Flow
Double blind single site pilot clinical trial conducted at academic medical center. Participants randomized to one of 4 arms by computer assignment conducted at independent site not enrolling subjects.
If participants were on hormone replacement at enrollment, needed to have 3 month washout period before randomization. Participants were required to be nonsmokers, have intact uterus, and be menopausal. Screening ultrasound of the uterus, bone density, screening metabolic panel, and baseline mammogram were required.
Participant milestones
| Measure |
Participants Randomized to Arm 1
Participants in Arm 1 received Prempro, premarin .45mg, provera 1.5mg conjugated estrogens, medroxyprogesterone acetate Prempro, premarin, provera conjugated estrogens, medroxyprogesterone acetate: Prempro, premarin .45mg, provera 1.5mg conjugated estrogens, medroxyprogesterone acetate
|
Participants Randomized to Arm 2
Participants in Arm 2 received compounded Estradiol .5mg, estriol 210mg, progesterone 100mg
Estradiol , estriol , progesterone: Estradiol .5mg, estriol 210mg, progesterone 100mg
|
Participants Randomized to Arm 3
Participants in Arm 3 received compounded estriol 2.5mg, progesterone 100mg
estriol, progesterone: estriol 2.5mg, progesterone 100mg
|
Participants Randomized to Arm 4
estradiol,progesterone
estradiol,progesterone: estradiol,progesterone
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
5
|
4
|
|
Overall Study
COMPLETED
|
2
|
1
|
2
|
4
|
|
Overall Study
NOT COMPLETED
|
4
|
5
|
3
|
0
|
Reasons for withdrawal
| Measure |
Participants Randomized to Arm 1
Participants in Arm 1 received Prempro, premarin .45mg, provera 1.5mg conjugated estrogens, medroxyprogesterone acetate Prempro, premarin, provera conjugated estrogens, medroxyprogesterone acetate: Prempro, premarin .45mg, provera 1.5mg conjugated estrogens, medroxyprogesterone acetate
|
Participants Randomized to Arm 2
Participants in Arm 2 received compounded Estradiol .5mg, estriol 210mg, progesterone 100mg
Estradiol , estriol , progesterone: Estradiol .5mg, estriol 210mg, progesterone 100mg
|
Participants Randomized to Arm 3
Participants in Arm 3 received compounded estriol 2.5mg, progesterone 100mg
estriol, progesterone: estriol 2.5mg, progesterone 100mg
|
Participants Randomized to Arm 4
estradiol,progesterone
estradiol,progesterone: estradiol,progesterone
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
0
|
0
|
|
Overall Study
Adverse Event
|
0
|
2
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
0
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
0
|
|
Overall Study
cancer unrelated to study discovered
|
1
|
0
|
1
|
0
|
Baseline Characteristics
Bioidentical 'Natural' Hormone Evaluation in Early Menopause
Baseline characteristics by cohort
| Measure |
Study Arm 1
n=6 Participants
Prempro, premarin .45mg, provera 1.5mg conjugated estrogens, medroxyprogesterone acetate
Prempro, premarin, provera conjugated estrogens, medroxyprogesterone acetate: Prempro, premarin .45mg, provera 1.5mg conjugated estrogens, medroxyprogesterone acetate
|
Study Arm 2
n=6 Participants
Estradiol .5mg, estriol 210mg, progesterone 100mg
Estradiol , estriol , progesterone: Estradiol .5mg, estriol 210mg, progesterone 100mg
|
Study Arm 3
n=5 Participants
estriol 2.5mg, progesterone 100mg
estriol, progesterone: estriol 2.5mg, progesterone 100mg
|
Study Arm 4
n=4 Participants
estradiol,progesterone
estradiol,progesterone: estradiol,progesterone
|
Total
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
21 Participants
n=21 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
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
6 participants
n=7 Participants
|
5 participants
n=5 Participants
|
4 participants
n=4 Participants
|
21 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline and month 12To determine if bioidentical hormone replacement therapy is associated with change in lipid profiles (surrogate marker for cardiovascular disease) when compared to Prempro and provide safety data to proceed to larger trial. This was determined by evaluating lipid levels at baseline and during the 12-month treatment period. Participants' values were averaged at baseline and again at 12 months; the average of the baseline value was subtracted from the average at completion.
Outcome measures
| Measure |
Study Arm 1
n=2 Participants
Menopausal women in first seven years of menopause randomized to arm 1 receive conjugated equine estrogens 0.45 mg combined with medroxyprogesteroneacetate 1.5 mg placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
Study Arm 2
n=1 Participants
Menopausal women in first seven years of menopause randomized to arm 2 estradiol .5mg, estriol 2.0mg, progesterone 100mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
Study Arm 3
n=2 Participants
Menopausal women in first seven years of menopause randomized to arm 3 estriol 2.5mg, progesterone 100mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
Study Arm 4
n=4 Participants
Menopausal women in first seven years of menopause randomized to arm 4 estradiol 0.5 mg, progesterone 100 mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
|---|---|---|---|---|
|
Change in Total Cholesterol
|
221.5 mg/dL
Standard Deviation 12.5
|
221.5 mg/dL
Standard Deviation 0
|
223 mg/dL
Standard Deviation 26
|
165.5 mg/dL
Standard Deviation 11
|
PRIMARY outcome
Timeframe: Baseline and month 12Baseline and 12 month follow up endovaginal ultrasound(completed at study site only) to evaluate endometrial stripe thickness for change on hormone therapy for all 4 arms. Endometrial thickness was measured in millimeters at baseline and again at 12 month completion. The average of the baseline value was subtracted from the average at completion for each group and reported in mm. Single participant in Arm 2: compared baseline to completion.
Outcome measures
| Measure |
Study Arm 1
n=2 Participants
Menopausal women in first seven years of menopause randomized to arm 1 receive conjugated equine estrogens 0.45 mg combined with medroxyprogesteroneacetate 1.5 mg placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
Study Arm 2
n=1 Participants
Menopausal women in first seven years of menopause randomized to arm 2 estradiol .5mg, estriol 2.0mg, progesterone 100mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
Study Arm 3
n=2 Participants
Menopausal women in first seven years of menopause randomized to arm 3 estriol 2.5mg, progesterone 100mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
Study Arm 4
n=4 Participants
Menopausal women in first seven years of menopause randomized to arm 4 estradiol 0.5 mg, progesterone 100 mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
|---|---|---|---|---|
|
Endometrial Measurement
|
13.0 mm
Standard Deviation 0
|
10.0 mm
Standard Deviation 0
|
2.5 mm
Standard Deviation 0.7
|
3.1 mm
Standard Deviation 0.7
|
PRIMARY outcome
Timeframe: baseline and month 12Comparison at baseline and month 12 by descriptive analysis of breast mammograms. Assessing for changes in density and/or lesions for risk of breast stimulation from hormone replacement therapy. Mammogram readings for participants completing study in descriptive terms. Looking for significant change in breast tissue while on hormone therapy for 12 months. Those who had no change are counted below.
Outcome measures
| Measure |
Study Arm 1
n=2 Participants
Menopausal women in first seven years of menopause randomized to arm 1 receive conjugated equine estrogens 0.45 mg combined with medroxyprogesteroneacetate 1.5 mg placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
Study Arm 2
n=1 Participants
Menopausal women in first seven years of menopause randomized to arm 2 estradiol .5mg, estriol 2.0mg, progesterone 100mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
Study Arm 3
n=2 Participants
Menopausal women in first seven years of menopause randomized to arm 3 estriol 2.5mg, progesterone 100mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
Study Arm 4
n=4 Participants
Menopausal women in first seven years of menopause randomized to arm 4 estradiol 0.5 mg, progesterone 100 mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
|---|---|---|---|---|
|
Number of Participants Without Change in Baseline and Follow up Mammograms
|
2 Participants
|
1 Participants
|
2 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: baseline and 12 monthsPopulation: Only 7 participants completed both the baseline bone density and 12-month follow up bone density resulting in a discrepancy in evaluable numbers compared to other outcome measures.
Comparison at baseline and month 12 by descriptive analysis of bone density. Assessing for changes in density related to hormone replacement therapy. Bone density readings for participants completing study in descriptive terms. Looking for significant change in bone density while on hormone therapy for 12 months. Those who had no change are counted below.
Outcome measures
| Measure |
Study Arm 1
n=1 Participants
Menopausal women in first seven years of menopause randomized to arm 1 receive conjugated equine estrogens 0.45 mg combined with medroxyprogesteroneacetate 1.5 mg placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
Study Arm 2
n=1 Participants
Menopausal women in first seven years of menopause randomized to arm 2 estradiol .5mg, estriol 2.0mg, progesterone 100mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
Study Arm 3
n=2 Participants
Menopausal women in first seven years of menopause randomized to arm 3 estriol 2.5mg, progesterone 100mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
Study Arm 4
n=3 Participants
Menopausal women in first seven years of menopause randomized to arm 4 estradiol 0.5 mg, progesterone 100 mg dosed orally / day placed in a placebo capsule to disguise contents from participant and study team. Drug dosed daily for 1 year. Screening FSH and PAP. Baseline mammogram, bone density, pelvic ultrasound, EKG, blood work for cholesterol panel (surrogate marker for cardiovascular disease), BUN/Creatinine. Repeated at 12 months. Safety check at 6 months includes BUN/creatinine, EKG, cholesterol panel, estradiol, progesterone levels.
|
|---|---|---|---|---|
|
Number of Participants Without Change in Baseline and Follow up Bone Density
|
1 Participants
|
1 Participants
|
2 Participants
|
3 Participants
|
Adverse Events
Study Arm 1
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Study Arm 2
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Study Arm 3
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Study Arm 4
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Study Arm 1
n=6 participants at risk
Prempro, premarin .45mg, provera 1.5mg conjugated estrogens, medroxyprogesterone acetate
Prempro, premarin, provera conjugated estrogens, medroxyprogesterone acetate: Prempro, premarin .45mg, provera 1.5mg conjugated estrogens, medroxyprogesterone acetate
|
Study Arm 2
n=6 participants at risk
Estradiol .5mg, estriol 210mg, progesterone 100mg
Estradiol , estriol , progesterone: Estradiol .5mg, estriol 210mg, progesterone 100mg
|
Study Arm 3
n=5 participants at risk
estriol 2.5mg, progesterone 100mg
estriol, progesterone: estriol 2.5mg, progesterone 100mg
|
Study Arm 4
n=4 participants at risk
estradiol,progesterone
estradiol,progesterone: estradiol,progesterone
|
|---|---|---|---|---|
|
Reproductive system and breast disorders
Abnormal vaginal bleeding
|
0.00%
0/6 • Each participant had monitoring for adverse events from enrollment through the 1 year on trial.
|
16.7%
1/6 • Number of events 1 • Each participant had monitoring for adverse events from enrollment through the 1 year on trial.
|
40.0%
2/5 • Number of events 2 • Each participant had monitoring for adverse events from enrollment through the 1 year on trial.
|
0.00%
0/4 • Each participant had monitoring for adverse events from enrollment through the 1 year on trial.
|
|
Metabolism and nutrition disorders
Lethargy
|
0.00%
0/6 • Each participant had monitoring for adverse events from enrollment through the 1 year on trial.
|
16.7%
1/6 • Number of events 1 • Each participant had monitoring for adverse events from enrollment through the 1 year on trial.
|
0.00%
0/5 • Each participant had monitoring for adverse events from enrollment through the 1 year on trial.
|
0.00%
0/4 • Each participant had monitoring for adverse events from enrollment through the 1 year on trial.
|
Additional Information
Jeanne A Drisko, MD, CNS, FACN
University of Kansas Medical Center
Phone: 913-588-6208
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place