Trial Outcomes & Findings for Assessment of the Transfer of Using Levonorgestrel Intrauterine System (LNG IUS) as a Contraceptive to Using it as Part of Hormone Replacement Therapy (HRT). (NCT NCT00185458)
NCT ID: NCT00185458
Last Updated: 2013-11-27
Results Overview
Measured by using Subject Diaries (Subject Reported Data)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
394 participants
Primary outcome timeframe
Last 90 days in Contraception Phase and first 360 days in Hormone-Replacement Therapy (HRT) Phase
Results posted on
2013-11-27
Participant Flow
Only the subjects who reached menopause within max. of 4 years of the contraception phase were eligible for the Hormone-Replacement Therapy (HRT) phase. 58 subjects discontinued the study during the contraception phase before starting the HRT, and 168 subjects who started treatment did not reach menopause.
489 subjects were screened: 394 subjects started treatment and 95 subjects failed screening. Intent-to-treat (ITT) population included all subjects (N=394) who had the LNG IUS inserted, or for whom the insertion was attempted. 322 subjects without major protocol deviations were included in the Per protocol set (PPS).
Participant milestones
| Measure |
LNG IUS
Levonorgestrel Intrauterine System (LNG IUS) (initial in vitro release 20 µg/24h) intrauterine for minimum of 9 months and maximum of 60 months - 2 phases: a) Contraception Phase b) Hormone-Replacement Therapy (HRT) Phase. For outcome measures (vaginal bleeding variables), five 90-day Reference Periods were defined, which were used for comparison during statistical analysis: Reference Period -1 in Contraception Phase; Reference Periods 1-4 in HRT Phase. 90-day reference periods for analyzing vaginal bleeding data are defined by World Health Organization (WHO) guideline. Reference Period -1 is the last 90-day reference period that the subject had before starting the HRT. Reference Period 1 covers the first 90-days of the HRT phase, Reference Period 2 covers days 91 to 180, Reference Period 3 days 181 to 270, and Reference Period 4 days 271 to 360 of the HRT phase.
|
|---|---|
|
Contraception Phase
STARTED
|
394
|
|
Contraception Phase
COMPLETED
|
336
|
|
Contraception Phase
NOT COMPLETED
|
58
|
|
HRT Phase
STARTED
|
168
|
|
HRT Phase
COMPLETED
|
141
|
|
HRT Phase
NOT COMPLETED
|
27
|
Reasons for withdrawal
| Measure |
LNG IUS
Levonorgestrel Intrauterine System (LNG IUS) (initial in vitro release 20 µg/24h) intrauterine for minimum of 9 months and maximum of 60 months - 2 phases: a) Contraception Phase b) Hormone-Replacement Therapy (HRT) Phase. For outcome measures (vaginal bleeding variables), five 90-day Reference Periods were defined, which were used for comparison during statistical analysis: Reference Period -1 in Contraception Phase; Reference Periods 1-4 in HRT Phase. 90-day reference periods for analyzing vaginal bleeding data are defined by World Health Organization (WHO) guideline. Reference Period -1 is the last 90-day reference period that the subject had before starting the HRT. Reference Period 1 covers the first 90-days of the HRT phase, Reference Period 2 covers days 91 to 180, Reference Period 3 days 181 to 270, and Reference Period 4 days 271 to 360 of the HRT phase.
|
|---|---|
|
Contraception Phase
Adverse Event
|
37
|
|
Contraception Phase
Lost to Follow-up
|
10
|
|
Contraception Phase
Protocol Violation
|
2
|
|
Contraception Phase
Physician Decision
|
2
|
|
Contraception Phase
Withdrawal by Subject
|
7
|
|
HRT Phase
Adverse Event
|
18
|
|
HRT Phase
Lost to Follow-up
|
4
|
|
HRT Phase
Protocol Violation
|
2
|
|
HRT Phase
Withdrawal by Subject
|
3
|
Baseline Characteristics
Assessment of the Transfer of Using Levonorgestrel Intrauterine System (LNG IUS) as a Contraceptive to Using it as Part of Hormone Replacement Therapy (HRT).
Baseline characteristics by cohort
| Measure |
LNG IUS
n=394 Participants
Levonorgestrel Intrauterine System (LNG IUS) (initial in vitro release 20 µg/24h) intrauterine for minimum of 9 months and maximum of 60 months - 2 phases: a) Contraception Phase b) Hormone-Replacement Therapy (HRT) Phase. For outcome measures (vaginal bleeding variables), five 90-day Reference Periods were defined, which were used for comparison during statistical analysis: Reference Period -1 in Contraception Phase; Reference Periods 1-4 in HRT Phase. 90-day reference periods for analyzing vaginal bleeding data are defined by World Health Organization (WHO) guideline. Reference Period -1 is the last 90-day reference period that the subject had before starting the HRT. Reference Period 1 covers the first 90-days of the HRT phase, Reference Period 2 covers days 91 to 180, Reference Period 3 days 181 to 270, and Reference Period 4 days 271 to 360 of the HRT phase.
|
|---|---|
|
Age Continuous
|
47.8 years
STANDARD_DEVIATION 1.42 • n=5 Participants
|
|
Sex: Female, Male
Female
|
394 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Last 90 days in Contraception Phase and first 360 days in Hormone-Replacement Therapy (HRT) PhasePopulation: Intention to treat population (ITT); all subjects with adequate bleeding diary data. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Measured by using Subject Diaries (Subject Reported Data)
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=165 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=154 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=151 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
n=141 Participants
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
n=132 Participants
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Number of Bleeding Days
|
0 Bleeding days
Interval 0.0 to 2.0
|
0 Bleeding days
Interval 0.0 to 1.0
|
0 Bleeding days
Interval 0.0 to 2.0
|
0 Bleeding days
Interval 0.0 to 0.0
|
0 Bleeding days
Interval 0.0 to 0.0
|
PRIMARY outcome
Timeframe: Last 90 days in Contraception Phase and first 360 days in HRT PhasePopulation: ITT; all subjects with adequate bleeding diary data. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Measured by using Subject Diaries (Subject Reported Data)
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=165 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=154 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=151 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
n=141 Participants
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
n=132 Participants
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Number of Spotting Days
|
4 Spotting days
Interval 0.0 to 11.0
|
4 Spotting days
Interval 0.0 to 10.0
|
2 Spotting days
Interval 0.0 to 9.0
|
1 Spotting days
Interval 0.0 to 5.0
|
0 Spotting days
Interval 0.0 to 6.0
|
PRIMARY outcome
Timeframe: Last 90 days in Contraception Phase and first 360 days in HRT PhasePopulation: ITT; all subjects eligible for the HRT
Definition of successful treatment: * Completion of HRT phase, and * Both, the number of bleeding days and the number of spotting days during HRT was equal to or less than during contraceptive phase, and * The number of bleeding days and the number of spotting days could be calculated for at least 3 out of the first 4 reference periods in HRT
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=168 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Percentage of Participants With Successful Treatment
|
31 Percentage of participants with success
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Women's Health Questionnaire (Total Score). For the Total score, the minimum is 36 and maximum is 144. A higher score means the distress and dysfunction are less pronounced.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=165 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=148 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=141 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Assessment of QOL as Measured by Women's Health Questionnaire
|
104.1 score on a scale
Standard Deviation 17.75
|
114.4 score on a scale
Standard Deviation 16.64
|
112.9 score on a scale
Standard Deviation 16.32
|
—
|
—
|
SECONDARY outcome
Timeframe: At entry, at 2 years, at 4 yearsPopulation: ITT. Kaplan-Meier estimator given.
Percentage of subjects continuing in the study at the given time points.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=394 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Continuation Rates
At Entry
|
100.0 Percentage of participants continuing
|
—
|
—
|
—
|
—
|
|
Continuation Rates
At 2 Years
|
72.3 Percentage of participants continuing
|
—
|
—
|
—
|
—
|
|
Continuation Rates
At 4 Years
|
23.6 Percentage of participants continuing
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=168 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=147 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=139 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Progestogenic Symptom 1: Headache (as Measured by a Visual Analogue Scale (VAS))
|
23.9 score on a scale
Standard Deviation 23.98
|
19.1 score on a scale
Standard Deviation 22.57
|
18.2 score on a scale
Standard Deviation 23.00
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=167 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=147 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=139 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Progestogenic Symptom 2: Depressive Mood (as Measured by a VAS)
|
22.3 score on a scale
Standard Deviation 25.69
|
11.8 score on a scale
Standard Deviation 17.31
|
14.6 score on a scale
Standard Deviation 22.10
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=168 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=147 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=139 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Progestogenic Symptom 3: Acne or Greasy Skin (as Measured by a VAS)
|
8.9 score on a scale
Standard Deviation 14.02
|
7.3 score on a scale
Standard Deviation 15.38
|
7.6 score on a scale
Standard Deviation 15.41
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=168 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=147 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=139 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Progestogenic Symptom 4: Nausea (as Measured by a VAS)
|
7.5 score on a scale
Standard Deviation 13.57
|
5.3 score on a scale
Standard Deviation 11.96
|
6.7 score on a scale
Standard Deviation 15.32
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=168 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=147 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=139 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Progestogenic Symptom 5: Edema (as Measured by a VAS)
|
15.7 score on a scale
Standard Deviation 20.30
|
12.3 score on a scale
Standard Deviation 18.93
|
11.7 score on a scale
Standard Deviation 17.65
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=166 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=144 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=135 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Progestogenic Symptom 6: Decreased Libido (as Measured by a VAS)
|
24.9 score on a scale
Standard Deviation 26.29
|
15.6 score on a scale
Standard Deviation 22.06
|
17.5 score on a scale
Standard Deviation 21.13
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=167 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=147 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=138 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Climacteric Symptom 1: Hot Flushes (as Measured by a VAS)
|
39.9 score on a scale
Standard Deviation 30.21
|
9.4 score on a scale
Standard Deviation 14.88
|
11.3 score on a scale
Standard Deviation 18.65
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=167 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=147 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=138 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Climacteric Symptom 2: Sweating Episodes (as Measured by a VAS)
|
43.0 score on a scale
Standard Deviation 29.40
|
14.0 score on a scale
Standard Deviation 19.95
|
17.0 score on a scale
Standard Deviation 21.97
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=167 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=147 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=138 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Climacteric Symptom 3: Vaginal Dryness (as Measured by a VAS)
|
22.8 score on a scale
Standard Deviation 27.96
|
13.1 score on a scale
Standard Deviation 20.93
|
16.7 score on a scale
Standard Deviation 23.00
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=167 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=147 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=138 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Climacteric Symptom 4: Sleep Problems (as Measured by a VAS)
|
39.4 score on a scale
Standard Deviation 29.71
|
17.1 score on a scale
Standard Deviation 21.34
|
19.9 score on a scale
Standard Deviation 23.93
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=167 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=147 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=138 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Climacteric Symptom 5: Irritability (as Measured by a VAS)
|
33.1 score on a scale
Standard Deviation 27.40
|
17.2 score on a scale
Standard Deviation 19.47
|
19.4 score on a scale
Standard Deviation 20.26
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=167 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=147 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=138 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Climacteric Symptom 6: Breast Tension (as Measured by a VAS)
|
15.5 score on a scale
Standard Deviation 22.16
|
13.5 score on a scale
Standard Deviation 20.39
|
13.0 score on a scale
Standard Deviation 19.42
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=168 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=147 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=139 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Progestogenic Symptom 7: Hair Loss (as Measured by a VAS)
|
10.0 score on a scale
Standard Deviation 15.14
|
9.3 score on a scale
Standard Deviation 16.69
|
9.0 score on a scale
Standard Deviation 13.63
|
—
|
—
|
SECONDARY outcome
Timeframe: Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phasePopulation: ITT. Only the subjects that were eligible for the HRT are included. Due to dropouts and missing data the number of subjects do not necessarily sum up to 168, the number of subjects of the ITT, who qualified for the HRT phase.
Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100.
Outcome measures
| Measure |
Reference Period -1 (Contraception Phase)
n=168 Participants
Patient assessment within the last 90-days before starting the HRT
|
Reference Period 1 (HRT Phase)
n=146 Participants
Patient assessment within the first 90-days of the HRT phase
|
Reference Period 2 (HRT Phase)
n=139 Participants
Patient assessment within day 91 to 180 of the HRT phase
|
Reference Period 3 (HRT Phase)
Patient assessment within day 181 to 270 of the HRT phase
|
Reference Period 4 (HRT Phase)
Patient assessment within day 271 to 360 of the HRT phase
|
|---|---|---|---|---|---|
|
Progestogenic Symptom 8: Greasy Hair (as Measured by a VAS)
|
14.0 score on a scale
Standard Deviation 20.60
|
11.5 score on a scale
Standard Deviation 18.85
|
11.1 score on a scale
Standard Deviation 18.93
|
—
|
—
|
Adverse Events
LNG IUS
Serious events: 25 serious events
Other events: 357 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LNG IUS
n=394 participants at risk
Levonorgestrel Intrauterine System (LNG IUS) (initial in vitro release 20 µg/24h) intrauterine for minimum of 9 months and maximum of 60 months - 2 phases: a) Contraception Phase b) Hormone-Replacement Therapy (HRT) Phase. For outcome measures (vaginal bleeding variables), five 90-day Reference Periods were defined, which were used for comparison during statistical analysis: Reference Period -1 in Contraception Phase; Reference Periods 1-4 in HRT Phase. 90-day reference periods for analyzing vaginal bleeding data are defined by World Health Organization (WHO) guideline. Reference Period -1 is the last 90-day reference period that the subject had before starting the HRT. Reference Period 1 covers the first 90-days of the HRT phase, Reference Period 2 covers days 91 to 180, Reference Period 3 days 181 to 270, and Reference Period 4 days 271 to 360 of the HRT phase.
|
|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
1.0%
4/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.51%
2/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Gastrointestinal disorders
Abdominal pain
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Renal and urinary disorders
Bladder prolapse
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Bronchitis
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Nervous system disorders
Cerebrovascular accident
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Surgical and medical procedures
Cholecystectomy
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Reproductive system and breast disorders
Colpocele
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Gastrointestinal disorders
Crohn's disease
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Reproductive system and breast disorders
Cystocele
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Gastrointestinal disorders
Ileus
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Surgical and medical procedures
Jejunectomy
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Injury, poisoning and procedural complications
Muscle rupture
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Cardiac disorders
Palpitations
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Musculoskeletal and connective tissue disorders
Periarthritis
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Pneumonia
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Surgical and medical procedures
Scar excision
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Surgical and medical procedures
Splenectomy
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Surgical and medical procedures
Thyroidectomy
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Nervous system disorders
Transient ischaemic attack
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Surgical and medical procedures
Varicose vein operation
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Vascular disorders
Venous thrombosis limb
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Gastrointestinal disorders
Volvulus
|
0.25%
1/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
Other adverse events
| Measure |
LNG IUS
n=394 participants at risk
Levonorgestrel Intrauterine System (LNG IUS) (initial in vitro release 20 µg/24h) intrauterine for minimum of 9 months and maximum of 60 months - 2 phases: a) Contraception Phase b) Hormone-Replacement Therapy (HRT) Phase. For outcome measures (vaginal bleeding variables), five 90-day Reference Periods were defined, which were used for comparison during statistical analysis: Reference Period -1 in Contraception Phase; Reference Periods 1-4 in HRT Phase. 90-day reference periods for analyzing vaginal bleeding data are defined by World Health Organization (WHO) guideline. Reference Period -1 is the last 90-day reference period that the subject had before starting the HRT. Reference Period 1 covers the first 90-days of the HRT phase, Reference Period 2 covers days 91 to 180, Reference Period 3 days 181 to 270, and Reference Period 4 days 271 to 360 of the HRT phase.
|
|---|---|
|
Injury, poisoning and procedural complications
Procedural pain
|
29.7%
117/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Nervous system disorders
Headache
|
15.0%
59/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.9%
47/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Influenza
|
10.9%
43/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Reproductive system and breast disorders
Menopausal symptoms
|
7.9%
31/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Reproductive system and breast disorders
Ovarian cyst
|
7.9%
31/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Investigations
Smear cervix normal
|
7.9%
31/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Gastrointestinal disorders
Abdominal pain
|
7.6%
30/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
7.4%
29/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Vaginal candidiasis
|
7.4%
29/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Reproductive system and breast disorders
Breast pain
|
7.1%
28/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Reproductive system and breast disorders
Breast tenderness
|
6.9%
27/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
6.9%
27/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Cystitis
|
6.6%
26/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
6.6%
26/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Nasopharyngitis
|
6.1%
24/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Vascular disorders
Hypertension
|
5.8%
23/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.8%
23/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.1%
20/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Bronchitis
|
5.1%
20/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Psychiatric disorders
Depression
|
4.8%
19/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Reproductive system and breast disorders
Genital haemorrhage
|
4.8%
19/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Sinusitis
|
4.8%
19/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Psychiatric disorders
Sleep disorder
|
4.6%
18/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Investigations
Weight increased
|
4.3%
17/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Gastrointestinal disorders
Abdominal pain lower
|
4.1%
16/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Vaginitis bacterial
|
3.8%
15/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
General disorders
Fatigue
|
3.6%
14/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Vascular disorders
Hot flush
|
3.6%
14/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Reproductive system and breast disorders
Vaginal discharge
|
3.6%
14/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Vaginal infection
|
3.6%
14/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Nervous system disorders
Migraine
|
3.3%
13/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Upper respiratory tract infection
|
3.3%
13/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Gastrointestinal disorders
Abdominal distension
|
3.0%
12/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.0%
12/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Reproductive system and breast disorders
Metrorrhagia
|
3.0%
12/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Cardiac disorders
Palpitations
|
3.0%
12/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
2.8%
11/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Urinary tract infection
|
2.8%
11/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
2.8%
11/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Nervous system disorders
Dizziness
|
2.5%
10/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Reproductive system and breast disorders
Cervical polyp
|
2.3%
9/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Psychiatric disorders
Insomnia
|
2.3%
9/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Gastrointestinal disorders
Nausea
|
2.3%
9/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Skin and subcutaneous tissue disorders
Acne
|
2.0%
8/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Acute sinusitis
|
2.0%
8/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Reproductive system and breast disorders
Breast cyst
|
2.0%
8/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Respiratory tract infection
|
2.0%
8/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Infections and infestations
Tooth infection
|
2.0%
8/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
|
Reproductive system and breast disorders
Vulvovaginal pruritus
|
2.0%
8/394 • The data covers the entire treatment period (contraception phase + HRT phase).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The investigators agree to allow the sponsor to review any manuscripts and to negotiate the times and forums of their publication.
- Publication restrictions are in place
Restriction type: OTHER