Trial Outcomes & Findings for Mirena and Estrogen for Control of Perimenopause Symptoms and Ovulation Suppression (NCT NCT01613131)

NCT ID: NCT01613131

Last Updated: 2015-12-02

Results Overview

The Hot Flash Related Daily Interference Scale (HFRDIS) is a ten item scale measuring degree to which hot flashes interfere with 9 daily activities (work, social, leisure, sleep, mood, concentration, relations, sexuality, enjoyment of life, overall quality of life) over the prior week, each scored on a 10 point Likert scale. The total score is reported, and scores range from 0-100, 100 being the worst outcome.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 39 participants
• Primary outcome timeframe: Day 0
• Results posted on: 2015-12-02

Participant Flow

Women were recruited from the University of Colorado Denver campus by direct physician referral or from advertisements in the University community.

Women using systemic hormonal contraception (patch, pill, ring) were required to have a 30 day hormone washout prior to placement. One subject signed the consent, but failed to meet the inclusion/exclusion criteria during the screening process. Thus, there were 39 women that were enrolled, but only 38 that started in the participant flow.

Participant milestones

Measure	Mirena + Estradiol Gel Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Overall Study STARTED	20	18
Overall Study COMPLETED	17	13
Overall Study NOT COMPLETED	3	5

Reasons for withdrawal

Measure	Mirena + Estradiol Gel Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Overall Study Withdrawal by Subject	3	5

Baseline Characteristics

Mirena and Estrogen for Control of Perimenopause Symptoms and Ovulation Suppression

Baseline characteristics by cohort

Measure	Mirena + Estradiol Gel n=20 Participants Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=18 Participants Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.	Total n=38 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
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants	18 Participants n=7 Participants	38 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	18 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	18 participants n=7 Participants	38 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0

The Hot Flash Related Daily Interference Scale (HFRDIS) is a ten item scale measuring degree to which hot flashes interfere with 9 daily activities (work, social, leisure, sleep, mood, concentration, relations, sexuality, enjoyment of life, overall quality of life) over the prior week, each scored on a 10 point Likert scale. The total score is reported, and scores range from 0-100, 100 being the worst outcome.

Outcome measures

Measure	Mirena + Estradiol Gel n=20 Participants Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=18 Participants Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Hot Flashes	10.3 scores on a scale Standard Error 2.653	7.944 scores on a scale Standard Error 2.85

PRIMARY outcome

Timeframe: Day 0

The Pittsburgh Sleep Quality Index (PSQI) is a 19-item scale designed to measure general sleep disturbances over the previous month (sleep wake patterns, duration of sleep, sleep latency, impact of poor sleep on daytime functioning, assesses specific problems contributing to poor sleep, including pain, urination, breathing difficulty, snoring, dreams, temperature). The global score is reported and ranges from 1-21, with higher scores being indicative of poorer sleep.

Outcome measures

Measure	Mirena + Estradiol Gel n=20 Participants Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=18 Participants Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Sleep	9.80 scores on a scale Standard Error 1.13	8.83 scores on a scale Standard Error 1.01

PRIMARY outcome

Timeframe: Day 0

Population: Two women in the Mirena + Placebo Gel did not provide complete data for this outcome measure; thus they were not included in the analysis for this timepoint.

The Center for Epidemiologic Studies-Depression Scale (CES-D) is a 20-item scale with 4-point Likert responses indicating frequency of symptoms over past week. Scores range from 0-60, with scores >16 considered indicative of depressive symptoms.

Outcome measures

Measure	Mirena + Estradiol Gel n=20 Participants Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=16 Participants Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Depression	9.8 scores on a scale Standard Error 1.34	11.31 scores on a scale Standard Error 2.27

PRIMARY outcome

Timeframe: Day 0

Population: One woman in the Mirena + Placebo Gel arm did not provide complete data for this outcome measure; thus she was not included in the analysis for this timepoint.

The Fatigue Severity Scale (FSS) was used to determine the degree to which night-time sleep difficulty manifested as daytime sleepiness. The FSS is a 9-item scale assessing fatigue over the past week, on a 7-point Likert scale (ranging from 1-7). It is scored by averaging the individual item scores, with higher scores indicating greater fatigue. Scores greater than or equal to 5.5 are generally indicative of insomnia with impaired daytime functioning.

Outcome measures

Measure	Mirena + Estradiol Gel n=20 Participants Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=17 Participants Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Fatigue	3.38 scores on a scale Standard Error .32	3.90 scores on a scale Standard Error .34

PRIMARY outcome

Timeframe: Day 90

Population: 3 women in the Mirena + Estradiol Gel arm, and 5 women in the Mirena + Placebo Gel did not provide complete data; thus, were not included in the analysis for this timepoint.

The Pittsburgh Sleep Quality Index (PSQI) is a 19-item scale designed to measure general sleep disturbances over the previous month (sleep wake patterns, duration of sleep, sleep latency, impact of poor sleep on daytime functioning, assesses specific problems contributing to poor sleep, including pain, urination, breathing difficulty, snoring, dreams, temperature). The global score is reported and ranges from 1-21, with higher scores being indicative of poorer sleep.

Outcome measures

Measure	Mirena + Estradiol Gel n=17 Participants Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=13 Participants Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Sleep	9.24 scores on a scale Standard Error 1.04	9.31 scores on a scale Standard Error 1.37

PRIMARY outcome

Timeframe: Day 140

Population: 5 women in the Mirena + Estradiol Gel arm, and 7 women in the Mirena + Placebo Gel did not provide complete data; thus, were not included in the analysis for this timepoint.

The Pittsburgh Sleep Quality Index (PSQI) is a 19-item scale designed to measure general sleep disturbances over the previous month (sleep wake patterns, duration of sleep, sleep latency, impact of poor sleep on daytime functioning, assesses specific problems contributing to poor sleep, including pain, urination, breathing difficulty, snoring, dreams, temperature). The global score is reported and ranges from 1-21, with higher scores being indicative of poorer sleep.

Outcome measures

Measure	Mirena + Estradiol Gel n=15 Participants Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=11 Participants Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Sleep	8.67 scores on a scale Standard Error 1.10	7.46 scores on a scale Standard Error 1.46

PRIMARY outcome

Timeframe: Day 90

Population: 3 women in the Mirena + Estradiol Gel arm, and 5 women in the Mirena + Placebo Gel did not provide complete data; thus, were not included in the analysis for this timepoint.

The Hot Flash Related Daily Interference Scale (HFRDIS) is a ten item scale measuring degree to which hot flashes interfere with 9 daily activities (work, social, leisure, sleep, mood, concentration, relations, sexuality, enjoyment of life, overall quality of life) over the prior week, each scored on a 10 point Likert scale. The total score is reported, and scores range from 0-100, 100 being the worst outcome.

Outcome measures

Measure	Mirena + Estradiol Gel n=17 Participants Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=13 Participants Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Hot Flashes	12.71 scores on a scale Standard Error 3.70	5.31 scores on a scale Standard Error 2.62

PRIMARY outcome

Timeframe: Day 140

Population: 3 women in the Mirena + Estradiol Gel arm, and 5 women in the Mirena + Placebo Gel did not provide data; thus, were not included in the analysis for this timepoint.

The Hot Flash Related Daily Interference Scale (HFRDIS) is a ten item scale measuring degree to which hot flashes interfere with 9 daily activities (work, social, leisure, sleep, mood, concentration, relations, sexuality, enjoyment of life, overall quality of life) over the prior week, each scored on a 10 point Likert scale. The total score is reported, and scores range from 0-100, 100 being the worst outcome.

Outcome measures

Measure	Mirena + Estradiol Gel n=17 Participants Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=13 Participants Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Hot Flashes	7.18 scores on a scale Standard Error 2.12	9.54 scores on a scale Standard Error 4.09

PRIMARY outcome

Timeframe: Day 90

Population: 4 women in the Mirena + Estradiol Gel arm, and 5 women in the Mirena + Placebo Gel did not provide complete data; thus, were not included in the analysis for this timepoint.

The Center for Epidemiologic Studies-Depression Scale (CES-D) is a 20-item scale with 4-point Likert responses indicating frequency of symptoms over past week. Scores range from 0-60, with scores >16 considered indicative of depressive symptoms.

Outcome measures

Measure	Mirena + Estradiol Gel n=16 Participants Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=13 Participants Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Depression	9.69 scores on a scale Standard Error 1.46	11.46 scores on a scale Standard Error 2.92

PRIMARY outcome

Timeframe: Day 140

Population: 3 women in the Mirena + Estradiol Gel arm, and 6 women in the Mirena + Placebo Gel did not provide complete data; thus, were not included in the analysis for this timepoint.

The Center for Epidemiologic Studies-Depression Scale (CES-D) is a 20-item scale with 4-point Likert responses indicating frequency of symptoms over past week. Scores range from 0-60, with scores >16 considered indicative of depressive symptoms.

Outcome measures

Measure	Mirena + Estradiol Gel n=17 Participants Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=12 Participants Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Depression	11.41 scores on a scale Standard Error 1.80	12.08 scores on a scale Standard Error 2.56

PRIMARY outcome

Timeframe: Day 90

Population: 3 women in the Mirena + Estradiol Gel arm, and 6 women in the Mirena + Placebo Gel did not provide complete data; thus, were not included in the analysis for this timepoint.

The Fatigue Severity Scale (FSS) was used to determine the degree to which night-time sleep difficulty manifested as daytime sleepiness. The FSS is a 9-item scale assessing fatigue over the past week, on a 7-point Likert scale (ranging from 1-7). It is scored by averaging the individual item scores, with higher scores indicating greater fatigue. Scores greater than or equal to 5.5 are generally indicative of insomnia with impaired daytime functioning.

Outcome measures

Measure	Mirena + Estradiol Gel n=17 Participants Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=12 Participants Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Fatigue	3.54 scores on a scale Standard Error .34	3.80 scores on a scale Standard Error .35

PRIMARY outcome

Timeframe: Day 140

Population: 3 women in the Mirena + Estradiol Gel arm, and 5 women in the Mirena + Placebo Gel did not provide complete data; thus, were not included in the analysis for this timepoint.

The Fatigue Severity Scale (FSS) was used to determine the degree to which night-time sleep difficulty manifested as daytime sleepiness. The FSS is a 9-item scale assessing fatigue over the past week, on a 7-point Likert scale (ranging from 1-7). It is scored by averaging the individual item scores, with higher scores indicating greater fatigue. Scores greater than or equal to 5.5 are generally indicative of insomnia with impaired daytime functioning.

Outcome measures

Measure	Mirena + Estradiol Gel n=17 Participants Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=13 Participants Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
Fatigue	2.78 scores on a scale Standard Error .27	3.90 scores on a scale Standard Error .39

Adverse Events

Mirena + Estradiol Gel

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Mirena + Placebo Gel

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Mirena + Estradiol Gel n=20 participants at risk Subjects will be assigned to use of Estradiol gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Estradiol: Topical, .06%, Applied once daily for 50 days.	Mirena + Placebo Gel n=18 participants at risk Subjects will be assigned to use of placebo gel for use with Mirena. Mirena: Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months). Placebo Gel: Topical Gel, Applied once daily for 50 days, Placebo comparator.
General disorders Mood changes	5.0% 1/20 • Number of events 1 • 140 days	5.6% 1/18 • Number of events 1 • 140 days

Additional Information

Chanel Mansfield

University of Colorado Denver

Phone: 303-724-6501

Email: chanel.mansfield@ucdenver.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place