Assessment of the Transfer of Using Levonorgestrel Intrauterine System (LNG IUS) as a Contraceptive to Using it as Part of Hormone Replacement Therapy (HRT).

Study Overview
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Brief Summary
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The study has been designed to look at the transfer from using LNG IUS for contraception only, in reproductive age to using it for endometrial protection in menopausal age. The main area of interest in the study is the pattern of any vaginal bleeding that occurs.

Detailed Description
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The study has previously been posted by Schering AG, Germany. Schering AG, Germany has been renamed to Bayer HealthCare AG, Germany. Bayer HealthCare AG, Germany is the sponsor of the trial.

Official Title
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A 60-month Non-comparative Study on Bleeding Profiles With Levonorgestrel Intrauterine System in Transition From Reproductive Age Contraception to Menopause Age Endometrial Protection During Estrogen Replacement Therapy.

Conditions
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Menopause

Intervention / Treatment
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* Drug: LNG IUS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with intact uterus, regular menstrual cycles and no previous or current climacteric symptoms. Exclusion Criteria: Pregnancy or lactation. Previous pelvic infections. Abnormal bleeding. Abnormal uterine cavity. Uterine polyps. Genital cancer. Liver diseases. Alcoholism or drug abuse.

Ages Eligible for Study
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Minimum Age: 46 Years
Maximum Age: 51 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LNG IUS<br>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. | Drug: LNG IUS<br>* 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) 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 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Bleeding Days | Measured by using Subject Diaries (Subject Reported Data) | Last 90 days in Contraception Phase and first 360 days in Hormone-Replacement Therapy (HRT) Phase | 
| Number of Spotting Days | Measured by using Subject Diaries (Subject Reported Data) | Last 90 days in Contraception Phase and first 360 days in HRT Phase | 
| Percentage of Participants With Successful Treatment | 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 | Last 90 days in Contraception Phase and first 360 days in HRT Phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of QOL as Measured by Women's Health Questionnaire | 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. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Continuation Rates | Percentage of subjects continuing in the study at the given time points. | At entry, at 2 years, at 4 years | 
| Progestogenic Symptom 1: Headache (as Measured by a Visual Analogue Scale (VAS)) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Progestogenic Symptom 2: Depressive Mood (as Measured by a VAS) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Progestogenic Symptom 3: Acne or Greasy Skin (as Measured by a VAS) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Progestogenic Symptom 4: Nausea (as Measured by a VAS) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Progestogenic Symptom 5: Edema (as Measured by a VAS) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Progestogenic Symptom 6: Decreased Libido (as Measured by a VAS) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Climacteric Symptom 1: Hot Flushes (as Measured by a VAS) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Climacteric Symptom 2: Sweating Episodes (as Measured by a VAS) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Climacteric Symptom 3: Vaginal Dryness (as Measured by a VAS) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Climacteric Symptom 4: Sleep Problems (as Measured by a VAS) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Climacteric Symptom 5: Irritability (as Measured by a VAS) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Climacteric Symptom 6: Breast Tension (as Measured by a VAS) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Progestogenic Symptom 7: Hair Loss (as Measured by a VAS) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase | 
| Progestogenic Symptom 8: Greasy Hair (as Measured by a VAS) | Higher value means the symptom is more pronounced. Minimum is 0, maximum is 100. | Last measurement before start of HRT phase, 6 months after start of HRT phase, 12 month after start of HRT phase |