Trial Outcomes & Findings for A Treatment Study for Premenstrual Syndrome (PMS) (NCT NCT00001259)
NCT ID: NCT00001259
Last Updated: 2023-03-02
Results Overview
The Beck Depression Inventory (BDI) is a 21-item, self-report rating inventory that measures the severity of symptoms accompanying depression. Each item has a minimum score of 0 and a maximum score of 3, with higher numbers consistent with more severe symptoms. The score of each item is summed to amount the overall BDI score, with a minimum score of 0 and a maximum score of 63. Higher BDI scores are consistent with more severe depression. Score of 16 or greater is consistent with clinical depression. Each participant completed the BDI every 2 weeks during each of the study phases throughout the 6-month study. Outcome measures reported consist of the average of two BDI scores from each phase of the study: the last 4 weeks of the GnRH agonist alone; weeks 6 and 8 of placebo alone; during the 4-week long estradiol phase (weeks 2 and 4 of estradiol) and the 4-week long progesterone phase (weeks 2 and 4 of progesterone).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
60 participants
Primary outcome timeframe
Placebo: Weeks 6 and 8 of Placebo; Lupron only: Weeks 6 and 8 or 10 and 12; Estradiol or progesterone: Weeks 2 and 4
Results posted on
2023-03-02
Participant Flow
One participant signed consent but withdrew prior to study start
8 of 46 participants who completed Study 2, Phase 1 did not proceed to Study 2, Phase 2.
Participant milestones
| Measure |
Study 1, Phase 1, Assignment 1 - Placebo
As part of double Blind randomized trial, participants in Assignment 1 were randomized to 8 weeks of placebo (P) injections (1 injection per month). These participants then continued on to Study 2 after completion of 8 weeks of placebo injections.
|
Study 1, Phase 1, Assignment 2 - GnRH Agonist Injections (Lupron-L Only)
As part of double Blind randomized trial, participants in Assignment 2 were randomized to 8 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly. Those who exhibited a remission of symptoms after 8 weeks continued on to receive one more month of GnRH agonist treatment (12 weeks total) and then entered Study 1, Phase 2.
|
Study 1, Phase 2, Arm 1 - Estradiol, Then Progesterone
12 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly. Additionally, 4 weeks of transdermal Estradiol (100mcg/day by skin patch) and placebo suppositories. Week 5 involves 100mcg/day transdermal Estradiol and active Progesterone suppositories (200mg vaginally twice/day). Followed by 1-2 weeks (weeks 6-7) washout period. Then crossover to 5 weeks (week 8-12) of Progesterone suppositories (200mg vaginally twice/day) and placebo patches.
|
Study 1, Phase 2, Arm 2 - Progesterone, Then Estradiol
12 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly. Additionally, 5 weeks of Progesterone suppositories (200mg vaginally twice/day) and placebo patches. Followed by 1-2 weeks (weeks 6-7) washout period. Then crossover to 4 weeks (weeks 8-11) of transdermal Estradiol (100mcg/day by skin patch) and placebo suppositories. Week 12 involves 100mcg/day transdermal Estradiol and active Progesterone suppositories (200mg vaginally twice/day)
|
Study 2, Phase 1 - GnRH Agonist Injections (Lupron-L Only)
Eight to 12 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly.
|
Study 2, Phase 2, Arm 1 - Estradiol, Then Progesterone
12 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly. Additionally, 4 weeks of transdermal Estradiol (100mcg/day by skin patch) and placebo suppositories. Week 5 involves 100mcg/day transdermal Estradiol and active Progesterone suppositories (200mg vaginally twice/day). Followed by 1-2 weeks (weeks 6-7) washout period. Then crossover to 5 weeks (week 8-12) of Progesterone suppositories (200mg vaginally twice/day) and placebo patches.
|
Study 2, Phase 2, Arm 2 - Progesterone, Then Estradiol
12 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly. Additionally, 5 weeks of Progesterone suppositories (200mg vaginally twice/day) and placebo patches. Followed by 1-2 weeks (weeks 6-7) washout period. Then crossover to 4 weeks (weeks 8-11) of transdermal Estradiol (100mcg/day by skin patch) and placebo suppositories. Week 12 involves 100mcg/day transdermal Estradiol and active Progesterone suppositories (200mg vaginally twice/day)
|
|---|---|---|---|---|---|---|---|
|
Study 1
STARTED
|
10
|
10
|
0
|
0
|
0
|
0
|
0
|
|
Study 1
Completed Phase 1
|
10
|
10
|
0
|
0
|
0
|
0
|
0
|
|
Study 1
Started Phase 2
|
0
|
0
|
4
|
6
|
0
|
0
|
0
|
|
Study 1
Completed Phase 2
|
0
|
0
|
4
|
5
|
0
|
0
|
0
|
|
Study 1
Started Phase 2 - Crossover Arm
|
0
|
0
|
4
|
5
|
0
|
0
|
0
|
|
Study 1
Completed Phase 2 - Crossover Arm
|
0
|
0
|
4
|
5
|
0
|
0
|
0
|
|
Study 1
COMPLETED
|
10
|
10
|
0
|
0
|
0
|
0
|
0
|
|
Study 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Study 2
STARTED
|
0
|
0
|
0
|
0
|
48
|
0
|
0
|
|
Study 2
Completed Phase 1
|
0
|
0
|
0
|
0
|
46
|
0
|
0
|
|
Study 2
Started Phase 2
|
0
|
0
|
0
|
0
|
0
|
21
|
17
|
|
Study 2
Completed Phase 2
|
0
|
0
|
0
|
0
|
0
|
21
|
17
|
|
Study 2
Started Phase 2 - Crossover Arm
|
0
|
0
|
0
|
0
|
0
|
21
|
17
|
|
Study 2
Completed Phase 2 - Crossover Arm
|
0
|
0
|
0
|
0
|
0
|
21
|
17
|
|
Study 2
COMPLETED
|
0
|
0
|
0
|
0
|
46
|
0
|
0
|
|
Study 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
2
|
0
|
0
|
Reasons for withdrawal
| Measure |
Study 1, Phase 1, Assignment 1 - Placebo
As part of double Blind randomized trial, participants in Assignment 1 were randomized to 8 weeks of placebo (P) injections (1 injection per month). These participants then continued on to Study 2 after completion of 8 weeks of placebo injections.
|
Study 1, Phase 1, Assignment 2 - GnRH Agonist Injections (Lupron-L Only)
As part of double Blind randomized trial, participants in Assignment 2 were randomized to 8 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly. Those who exhibited a remission of symptoms after 8 weeks continued on to receive one more month of GnRH agonist treatment (12 weeks total) and then entered Study 1, Phase 2.
|
Study 1, Phase 2, Arm 1 - Estradiol, Then Progesterone
12 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly. Additionally, 4 weeks of transdermal Estradiol (100mcg/day by skin patch) and placebo suppositories. Week 5 involves 100mcg/day transdermal Estradiol and active Progesterone suppositories (200mg vaginally twice/day). Followed by 1-2 weeks (weeks 6-7) washout period. Then crossover to 5 weeks (week 8-12) of Progesterone suppositories (200mg vaginally twice/day) and placebo patches.
|
Study 1, Phase 2, Arm 2 - Progesterone, Then Estradiol
12 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly. Additionally, 5 weeks of Progesterone suppositories (200mg vaginally twice/day) and placebo patches. Followed by 1-2 weeks (weeks 6-7) washout period. Then crossover to 4 weeks (weeks 8-11) of transdermal Estradiol (100mcg/day by skin patch) and placebo suppositories. Week 12 involves 100mcg/day transdermal Estradiol and active Progesterone suppositories (200mg vaginally twice/day)
|
Study 2, Phase 1 - GnRH Agonist Injections (Lupron-L Only)
Eight to 12 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly.
|
Study 2, Phase 2, Arm 1 - Estradiol, Then Progesterone
12 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly. Additionally, 4 weeks of transdermal Estradiol (100mcg/day by skin patch) and placebo suppositories. Week 5 involves 100mcg/day transdermal Estradiol and active Progesterone suppositories (200mg vaginally twice/day). Followed by 1-2 weeks (weeks 6-7) washout period. Then crossover to 5 weeks (week 8-12) of Progesterone suppositories (200mg vaginally twice/day) and placebo patches.
|
Study 2, Phase 2, Arm 2 - Progesterone, Then Estradiol
12 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly. Additionally, 5 weeks of Progesterone suppositories (200mg vaginally twice/day) and placebo patches. Followed by 1-2 weeks (weeks 6-7) washout period. Then crossover to 4 weeks (weeks 8-11) of transdermal Estradiol (100mcg/day by skin patch) and placebo suppositories. Week 12 involves 100mcg/day transdermal Estradiol and active Progesterone suppositories (200mg vaginally twice/day)
|
|---|---|---|---|---|---|---|---|
|
Study 2
Adverse Event
|
0
|
0
|
0
|
0
|
2
|
0
|
0
|
Baseline Characteristics
A Treatment Study for Premenstrual Syndrome (PMS)
Baseline characteristics by cohort
| Measure |
Placebo
n=10 Participants
8 weeks of placebo (P) injections (one injection per month)
|
GnRH Agonist Injections (Lupron-L Only)
n=49 Participants
Eight to 12 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly before randomization to estradiol or progesterone arm in the crossover phase of the study
|
Total
n=59 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=93 Participants
|
49 Participants
n=4 Participants
|
59 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=93 Participants
|
49 Participants
n=4 Participants
|
59 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=93 Participants
|
47 Participants
n=4 Participants
|
57 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
15 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=93 Participants
|
29 Participants
n=4 Participants
|
39 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Placebo: Weeks 6 and 8 of Placebo; Lupron only: Weeks 6 and 8 or 10 and 12; Estradiol or progesterone: Weeks 2 and 4Population: Analyses included comparison of participants mean BDI scores during each phase of the study
The Beck Depression Inventory (BDI) is a 21-item, self-report rating inventory that measures the severity of symptoms accompanying depression. Each item has a minimum score of 0 and a maximum score of 3, with higher numbers consistent with more severe symptoms. The score of each item is summed to amount the overall BDI score, with a minimum score of 0 and a maximum score of 63. Higher BDI scores are consistent with more severe depression. Score of 16 or greater is consistent with clinical depression. Each participant completed the BDI every 2 weeks during each of the study phases throughout the 6-month study. Outcome measures reported consist of the average of two BDI scores from each phase of the study: the last 4 weeks of the GnRH agonist alone; weeks 6 and 8 of placebo alone; during the 4-week long estradiol phase (weeks 2 and 4 of estradiol) and the 4-week long progesterone phase (weeks 2 and 4 of progesterone).
Outcome measures
| Measure |
Placebo
n=10 Participants
8 weeks of placebo (P) injections (one injection per month)
|
GnRH Agonist Injections (Lupron-L Only)
n=48 Participants
Eight to 12 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly before randomization to estradiol or progesterone arm in the crossover phase of the study
|
Estradiol
n=48 Participants
4 weeks of transdermal Estradiol (100mcg/day by skin patch)
|
Progesterone
n=48 Participants
5 weeks of Progesterone suppositories (200mg vaginally twice/day)
|
|---|---|---|---|---|
|
Mean Beck Depression Inventory Score
|
2.6 score on a scale
Standard Deviation 2.6
|
3.0 score on a scale
Standard Deviation 3.8
|
5.3 score on a scale
Standard Deviation 5.3
|
3.6 score on a scale
Standard Deviation 5.7
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
GnRH Agonist Injections (Lupron-L Only)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Estradiol
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Progesterone
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 |
Placebo
n=10 participants at risk
8 weeks of placebo (P) injections (one injection per month)
|
GnRH Agonist Injections (Lupron-L Only)
n=58 participants at risk
Eight to 12 weeks of GnRH agonist treatment 3.75 mg given intramuscularly monthly before randomization to estradiol or progesterone arm in the crossover phase of the study
|
Estradiol
n=48 participants at risk
4 weeks of transdermal Estradiol (100mcg/day by skin patch)
|
Progesterone
n=48 participants at risk
5 weeks of Progesterone suppositories (200mg vaginally twice/day)
|
|---|---|---|---|---|
|
General disorders
Pain
|
0.00%
0/10 • 6 months
|
0.00%
0/58 • 6 months
|
4.2%
2/48 • Number of events 2 • 6 months
|
0.00%
0/48 • 6 months
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/10 • 6 months
|
1.7%
1/58 • Number of events 1 • 6 months
|
0.00%
0/48 • 6 months
|
0.00%
0/48 • 6 months
|
|
Metabolism and nutrition disorders
Fluid retention
|
0.00%
0/10 • 6 months
|
1.7%
1/58 • Number of events 1 • 6 months
|
0.00%
0/48 • 6 months
|
0.00%
0/48 • 6 months
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/10 • 6 months
|
0.00%
0/58 • 6 months
|
2.1%
1/48 • Number of events 1 • 6 months
|
0.00%
0/48 • 6 months
|
|
Psychiatric disorders
Mood disorder due to a general medical condition
|
0.00%
0/10 • 6 months
|
1.7%
1/58 • Number of events 1 • 6 months
|
0.00%
0/48 • 6 months
|
0.00%
0/48 • 6 months
|
|
Endocrine disorders
Genital atrophy
|
0.00%
0/10 • 6 months
|
1.7%
1/58 • Number of events 1 • 6 months
|
0.00%
0/48 • 6 months
|
0.00%
0/48 • 6 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place