Abstract
Objectives
Study Design
Results
Conclusions
Implications
Keywords
1. Introduction
- Bofill Rodriguez M
- Lethaby A
- Jordan V
2. Methods
2.1 Study design
Bayer. Mirena intrauterine delivery system 52 mg, https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/630004_2529710X1027_1_07. [Accessed 22 October 2020].
Pharmaceuticals and Medical Devices Agency. Good Post-marketing Study Practice Guidelines, https://www.pmda.go.jp/review-services/inspections/reexam-reeval/0004.html. [Accessed 14 April 2022]. [In Japanese]
2.1.1 Participants
2.1.2 Study visits
2.2 Study endpoints
2.3 Data collection
2.4 Additional analyses
2.5 Statistical analysis
3. Results
3.1 Patients

Age, years (median [Q1–Q3]) (n = 593) | 42.0 (38.0–45.0) |
BMI, kg/m2 (median [Q1–Q3]) (n = 503) | 21.2 (19.6–23.7) |
Childbirth history | |
Nullipara | 30 (5.0) |
Vaginal delivery | 405 (68.1) |
Caesarean section | 89 (15.0) |
Uterine cavity length, cm (median [Q1–Q3]) (n = 558) | 7.3 (7.0–8.0) |
Main indication for use of LNG-IUS | |
Heavy menstrual bleeding | 469 (78.8) |
Primary heavy menstrual bleeding | 133 (28.4) |
Secondary heavy menstrual bleeding | 336 (71.6) |
Dysmenorrhea | 377 (63.4) |
Primary dysmenorrhea | 118 (31.3) |
Secondary dysmenorrhea | 259 (68.7) |
History of gynecological surgery | |
None | 406 (68.2) |
Endometriosis | 46 (24.7) |
Uterine leiomyoma | 37 (19.9) |
Adenomyosis | 6 (3.2) |
Other | 114 (61.3) |
History of medication in the year prior to enrollment | |
None | 328 (55.1) |
Combined estrogen progestin agent (CHC) | 107 (40.4) |
Progestin-only agent | 51 (19.5) |
GnRH agonist | 52 (19.6) |
Estrogen-only agent | 4 (1.5) |
Danazol | 1 (0.3) |
Other | 90 (34.0) |
3.2 Safety
3.2.1 Evaluation of LNG-IUS insertion and pain
3.3 Clinical outcomes


3.4 Additional analyses
3.4.1 Expulsion risk
Univariate analysis | Multivariate analysis adjusted | Multivariate analysis stepwise | |
---|---|---|---|
Clinical features | OR (95% CI) | OR (95% CI) | OR (95% CI) |
Expulsion | |||
BMI: ≥25 / <25 kg/m2 | 3.25 (1.71–6.19) | 2.43 (1.20–4.89) | 2.74 (1.38–5.46) |
Adenomyosis: yes / no | 2.23 (1.26–3.92) | 2.34 (1.19–4.59) | 2.34 (1.22–4.51) |
Uterine cavity length: ≥8 / <8 cm | 3.08 (1.71–5.55) | 3.08 (1.54–6.16) | 3.44 (1.77–6.70) |
Uterine leiomyoma: yes / no | 2.09 (1.19–3.68) | 1.32 (0.64–2.69) | |
Age: ≥41 / <41 years | 1.86 (1.00–3.46) | 1.93 (0.89–4.16) |
3.4.2 Leiomyoma diameter and ultrasonography findings
4. Discussion
Japan Society for the Study of Obesity.
Johnson BA. FDA Mirena product label (full prescribing information). 2015. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021225s031lbl.pdf. [Accessed 9 March 2021].
Acknowledgements
Appendix. Supplementary materials
References
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Article info
Publication history
Footnotes
Funding: This work was supported by Bayer Yakuhin, Ltd., which actively participated in the study design and managed all operational aspects of the study, including monitoring data collection, statistical analyses, and writing of the report.
Data Statement: The data that support the findings of this study are available from the corresponding author, Tasuku Harada, upon reasonable request.
Author Contributions: Tasuku Harada, Ikuko Ota, Jo Kitawaki, Mikio Momoeda, Nagamasa Maeda, Shigeo Akira, Mikiko Umeyama, Toshiyuki Sunaya, and Kazufumi Hirano participated in the study conception and design. Mikiko Umeyama, Toshiyuki Sunaya, and Kazufumi Hirano collected and/or assembled the data. Tasuku Harada, Ikuko Ota, Jo Kitawaki, Mikio Momoeda, Nagamasa Maeda, Shigeo Akira, Mikiko Umeyama, Toshiyuki Sunaya, and Kazufumi Hirano did the data analysis and interpretation. Tasuku Harada, Ikuko Ota, Jo Kitawaki, Mikio Momoeda, Nagamasa Maeda, Shigeo Akira, Mikiko Umeyama, Toshiyuki Sunaya, and Kazufumi Hirano wrote and revised the manuscript. All authors made the final decision to submit the article for publication.
Declaration of Competing Interest: Tasuku Harada received personal fees from Bayer Yakuhin, Ltd. as a member of the Proper Use Advisory Committee for Mirena. Ikuko Ota received personal fees from Bayer Yakuhin, Ltd., and personal fees from Mochida Pharmaceutical Co., Ltd., and ASKA Pharmaceutical Co., Ltd., unrelated to the submitted work. Jo Kitawaki received personal fees from Bayer Yakuhin, Ltd., Mochida Pharmaceutical Co., Ltd. and ASKA Pharmaceutical Co., Ltd. a grant from Nichimo Biotics Co., Ltd. and has a patent of materials related to the treatment of endometriosis. Mikio Momoeda received personal fees from Bayer Yakuhin, Ltd. as a member of the Proper Use Advisory Committee for Mirena. Nagamasa Maeda received personal fees from Bayer Yakuhin, Ltd. as a member of the Proper Use Advisory Committee for Mirena. Shigeo Akira received personal fees from Bayer Yakuhin, Ltd. as a member of the Proper Use Advisory Committee for Mirena. Mikiko Umeyama, Toshiyuki Sunaya, and Kazufumi Hirano are employees of Bayer Yakuhin, Ltd.
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