Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000122358
Ethics application status
Approved
Date submitted
25/02/2008
Date registered
6/03/2008
Date last updated
17/03/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effect of the intra-uterine system, Mirena, on bone density
Scientific title
To compare the bone mineral density (BMD) of women who have used the levonorgestrel-releasing intra-uterine system Mirena for 4 to 6 years with women who have not been exposed to exogenous hormones or pregnancy for the previous 5 years.
Secondary ID [1] 288783 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bone mineral density 2866 0
Condition category
Condition code
Musculoskeletal 3001 3001 0 0
Osteoporosis

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Mirena use for 4 to 6 years. The Mirena intrauterine device (IUD) is a long acting contraceptive, an effective treatment for heavy menstrual bleeding and is approved for use with hormone replacement therapy (HRT) to provide endometrial protection. This T-shaped plastic device is placed within the uterus and releases the progestagen levonorgestrel into the uterine cavity with some absorption of levonorgestrel into the systemic circulation. Each device is registered for use as a contraceptive for up to 5 years and for control of menstrual bleeding it can be used for as long as it is effective. It can be replaced at the end of that time.
Intervention code [1] 2596 0
Diagnosis / Prognosis
Comparator / control treatment
Women in the control group had not used any exogenous hormones or been pregnant in the previous 5 years.
Control group
Active

Outcomes
Primary outcome [1] 3884 0
Bone mineral density (BMD) of lumbar spine and of the proximal femur measured by dual energy x-ray absorptiometry (DEXA) scan.
Timepoint [1] 3884 0
After 4 to 6 years
Secondary outcome [1] 6526 0
BMD Z-scores of lumbar spine and proximal femur
Timepoint [1] 6526 0
After 4 to 6 years of Mirena use for the Mirena users and after at least 5 years of no exogenous hormones or no pregnancy for the control group.

Eligibility
Key inclusion criteria
Women 30 to 47 years old who have used a Mirena for 4 to 6 years (exposed group) and women who have not been exposed to exogenous hormones or pregnancy for the previous 5 years (control group).
Minimum age
30 Years
Maximum age
47 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
History of chronic illness, metabolic bone disease. Taking medications known to affect bone or mineral metabolism, or any other hormonal medication taken in the previous 5 years. Pregnancy in the previous 5 years.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
Sample size calculation: Given a baseline value of 800 mg/cm2, an additional 0.5% decrease per year over four years of Mirena® use would be represented by a 16 mg/cm2 difference between the two groups. The standard deviation of BMD is estimated to be 47 mg/cm2, but around 75% of the variation in BMD is expected to be explainable by factors that we would be able to match on or adjust for, including age, smoking, BMI, parity, caffeine and calcium intake, contraceptive history, history of previous fracture, family history of osteoporosis (18). With this matching, 34 participants per group would be sufficient to provide 80% power to detect a 16 mg/cm2 difference in mean BMD with two-sided p<0.05 indicating statistical significance.
Statistical Analysis:
Matched demographics, health characteristics, behaviours, and dietary measures were described and then compared between groups using exact symmetry tests and Wilcoxon signed rank tests as appropriate.
Linear mixed models were used to compare groups in terms of BMD and z-score outcomes incorporating the matching at the individual level through a random effect for matched pairs. The adjusted models each included all variables with p<0.25 or that altered the effect size of interest by 15% or more from models otherwise only including group. These potential (residual) confounders were selected from:
age, BMI, smoking history, parity, total activity, and dietary measures (milk, bread, hard cheese and yoghurt). Subgroup analyses were undertaken for those pairs whose duration of Mirena® use was 4-6 years (removing 5 pairs) and a sensitivity analysis was performed restricted to only those pairs using the same DEXA scanner (removing 4 pairs).


Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/03/2008
Actual
4/03/2008
Date of last participant enrolment
Anticipated
Actual
30/09/2009
Date of last data collection
Anticipated
Actual
Sample size
Target
68
Accrual to date
Final
76
Recruitment outside Australia
Country [1] 802 0
New Zealand
State/province [1] 802 0

Funding & Sponsors
Funding source category [1] 3119 0
University
Name [1] 3119 0
University of Otago
Country [1] 3119 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
Union St
PO Box 56
Dunedin
Country
New Zealand
Secondary sponsor category [1] 2807 0
None
Name [1] 2807 0
N/A
Address [1] 2807 0
N/A
Country [1] 2807 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5096 0
Lower South Regional Ethics Committee
Ethics committee address [1] 5096 0
PO Box 5849
Dunedin
Ethics committee country [1] 5096 0
New Zealand
Date submitted for ethics approval [1] 5096 0
Approval date [1] 5096 0
15/02/2008
Ethics approval number [1] 5096 0

Summary
Brief summary
Objective: To determine if the levonorgestrel-releasing intrauterine system Mirena® affects bone mineral density (BMD).
Design: Cross-sectional study
Setting: Dunedin School of Medicine, University of Otago
Patients: BMD was compared between women aged 30 to 47 who had a current Mirena® inserted for 4 to 6 years and matched (age, BMI, smoking, and ethnicity) controls who had not been exposed to exogenous hormones or pregnancy for the previous 5 years.
Interventions: BMD was measured by double xray absorptiometry (DEXA) of the lumbar spine and proximal femur.
Main outcome measures: BMD of the lumbar spine and proximal femur. BMD z-scores were also recorded. Mixed models were used to estimate effects of Mirena® use with a random pair effect to accommodate the clustered design. Potential confounders were parity, gravidity, physical activity as well as matching variables that altered the effect by 15% or more.
Trial website
Trial related presentations / publications
Study presented as poster at the 2013 ASRM/IFFS conference in Boston, USA.
Reference: 'A cross sectional study of hip and spine bone mineral density in users of the levonorgestrel-releasing intrauterine system.' ASRM abstracts, Poster 572.
Fertility and Sterility. Vol 100, No.3, Supplement, S313. September 2013.
Public notes

Contacts
Principal investigator
Name 28399 0
Dr Dawn Miller
Address 28399 0
Department of Women's and Children's Health
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin
Country 28399 0
New Zealand
Phone 28399 0
+64 3 4740999 x58566
Fax 28399 0
+64 3 4709669
Email 28399 0
[email protected]
Contact person for public queries
Name 11556 0
Dr Dawn Miller
Address 11556 0
Departmentof Women's and Children's Health Dunedin School of Medicine University of Otago Great King St PO Box 56 Dunedin
Country 11556 0
New Zealand
Phone 11556 0
+64 3 4740999 x 58566
Fax 11556 0
+64 3 4709669
Email 11556 0
[email protected]
Contact person for scientific queries
Name 2484 0
Dr Dawn Miller
Address 2484 0
Department of Women's and Children's Health Dunedin School of Medicine University of Otago Great King St PO Box 56 Dunedin
Country 2484 0
New Zealand
Phone 2484 0
+64 3 4740999 x 58566
Fax 2484 0
+64 3 4709669
Email 2484 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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