Abstract
Objective
To compare the risk of all-cause death, hospitalizations (any cause), ectopic pregnancy,
pelvic inflammatory disease or infection, uterine perforation, device removal, neuro-psychiatric
drugs initiation, or new psychiatric visit(s) between levonorgestrel (LNG) 52 mg intrauterine
system (IUS) and copper intrauterine device (IUD) users in France.
Study design
We identified a historical cohort of women aged 20–55 years with a first dispensing
of either LNG 52 mg IUS or copper-IUD between January 1, 2010, and December 31, 2014,
in the French National Claims database, SNDS. We used propensity score matching to
balance the two groups on baseline sociodemographic and clinical characteristics to
minimize confounding. We estimated Cox proportional hazards models to compare health
outcomes between LNG 52 mg IUS and copper-IUDs users.
Results
We matched 9318 LNG 52 mg IUS users (mean age 36.2±6.8 years) to 10,185 copper-IUD
users (mean age 35.4±7.1 years). After matching and age-adjustment, LNG 52 mg IUS
users had a slightly higher risk of anxiolytic drugs initiation (HR 1.08, 95%CI 1.01–1.15)
and device removal (HR 1.05, 95%CI 1.01–1.10) compared to copper-IUD users, with no
differences for other studied outcomes.
Conclusion
French IUS users report slightly more anxiolytic treatment initiation and IUD removal
compared to copper-IUD users. These results are consistent with a potential pharmacovigilance
signal of anxiety-related disorders in LNG 52 mg IUS users.
Implications statement
In French LNG 52 mg IUS users, there was slightly more anxiolytic treatment initiation
and IUD removal compared to copper-IUD users. No risk difference was found for all-cause
death, hospitalizations, ectopic pregnancy, pelvic disorders, and uterine perforation.
We cannot exclude that the associations are related to differences in characteristics
of women who chose each type of type of IUD.
Keywords
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References
- Méthode contraceptives: Focus sur les méthodes les plus efficaces disponibles. Haute Autorité de Santé,
Paris, France2016https://www.has-sante.fr/portail/upload/docs/application/pdf/2013-03/synthese_methodes_contraceptives_format2clics.pdfDate accessed: September 7, 2018
- Les Françaises et la contraception: premières données du Baromètre santé 2016. Santé Publique Fr,
2017https://www.santepubliquefrance.fr/Actualites/Les-Francaises-et-la-contraception-premieres-donnees-du-Barometre-sante-2016Date accessed: September 7, 2018
- Safety and efficacy in parous women of a 52-mg levonorgestrel-medicated intrauterine device: a 7-year randomized comparative study with the TCu380A.Contraception. 2016; 93: 498-506https://doi.org/10.1016/j.contraception.2016.02.024
- LNG-IUS 12: a 19.5 levonorgestrel-releasing intrauterine system for prevention of pregnancy for up to five years.Expert Opin Drug Deliv. 2017; 14: 1131-1140https://doi.org/10.1080/17425247.2017.1353972
- Efficacy and safety of long-acting reversible Contraception.Drugs. 2011; 71: 969-980https://doi.org/10.2165/11591290-000000000-00000
- The safety of intrauterine devices among young women: a systematic review.Contraception. 2017; 95: 17-39https://doi.org/10.1016/j.contraception.2016.10.006
- The levonorgestrel-releasing intrauterine system: safety, efficacy, and patient acceptability.Ther Clin Risk Manag. 2009; 5: 561-574
- Understanding benefits and addressing misperceptions and barriers to intrauterine device access among populations in the United States.Patient Prefer Adherence. 2014; 8: 947-957https://doi.org/10.2147/PPA.S45710
- Stérilet hormonal Mirena: les Françaises dénoncent une omerta sur les effets secondaires.([Available from:])
- Stérilet Levonorgestrel 52 mg IUS : Les plaintes liées à de lourds effets secondaires se multiplient.([Available from:]) ([52 mg IUS -plaintes-liees-lourds-effets-secondaires-multiplient])
- The national healthcare system claims databases in France, SNIIRAM and EGB: powerful tools for pharmacoepidemiology.Pharmacoepidemiol Drug Saf. 2017; 26: 954-962https://doi.org/10.1002/pds.4233
- Les chiffres clés de la sécurité sociale 2014. Direction de la Sécurité sociale.http://www.securite-sociale.fr/IMG/pdf/chiffres_cles_ed_2016_web.pdfDate: 2015Date accessed: September 7, 2018
- The central role of the propensity score in observational studies for causal effects.Biometrika. 1983; 70: 41-55https://doi.org/10.1093/biomet/70.1.41
- Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples.Stat Med. 2009; 28: 3083-3107https://doi.org/10.1002/sim.3697
- News and Events - European Medicines Agency to review third- and fourth-generation combined oral contraceptives.([n.d.])http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/01/news_detail_001700.jsp&mid=WC0b01ac058004d5c1Date accessed: September 7, 2018
- Efficacy of contraceptive methods: a review of the literature.Eur J Contracept Reprod Health Care. 2010; 15: 4-16https://doi.org/10.3109/13625180903427675
- Comparative contraceptive effectiveness of levonorgestrel-releasing and copper intrauterine devices: the European active surveillance study for intrauterine devices.Contraception. 2015; 91: 280-283
- Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine devices in the European active surveillance study on intrauterine devices.Contraception. 2015; 91: 274-279
Rahib D, Le Guen M, Lydié N. Contraception – Quatre ans après la crise de la pilule, les évolutions se poursuivent [Internet]. Saint-Maurice, France: Santé Publique France; [cited 2019 Jan 7]. (Baromètre Sante 2016). Available from:] http://inpes.santepubliquefrance.fr/CFESBases/catalogue/pdf/1806.pdf
- Contraception chez l'homme et chez la femme. Haute Autorité de Santé, 2013
- Cohort study of psychiatric adverse events following exposure to Levonorgestrel-containing intrauterine devices in UK general practice.Drug Saf. 2018; : 1-8https://doi.org/10.1007/s40264-018-0683-x
- The levonorgestrel-releasing intrauterine device potentiates stress reactivity.Psychoneuroendocrinology. 2017; 80: 39-45
- Progesterone and women's anxiety across the menstrual cycle.Horm Behav. 2018; 102: 34-40
- Long-term safety, efficacy, and patient acceptability of the intrauterine copper T-380A contraceptive device.Int J Women's Health. 2010; 2: 211-220
- Review of the safety, efficacy and patient acceptability of the levonorgestrel-releasing intrauterine system.Patient Prefer Adherence. 2008; 2: 293-302
- French health insurance databases: what interest for medical research?.Rev Méd Interne. 2015; 36: 411-417https://doi.org/10.1016/j.revmed.2014.11.009
- French national health insurance information system and the permanent beneficiaries sample.Rev Epidemiol Sante Publique. 2010; 58: 286-290https://doi.org/10.1016/j.respe.2010.04.005
Article info
Publication history
Published online: March 11, 2019
Accepted:
February 21,
2019
Received in revised form:
February 21,
2019
Received:
September 10,
2018
Footnotes
☆Funding sources: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
☆☆Disclosure of potential conflicts of interest: The study was conducted in the context of a national pharmacovigilance follow-up for which the Centre de Pharmacovigilance de Bordeaux was appointed by the French Medicines Agency (Agence Nationale de Sécurité des Médicaments, ANSM). The ANSM had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication. This publication represents the views of the authors and does not necessarily represent the opinion of the ANSM.
★Dr. P. Bosco-Lévy, Dr. C. Langlade, Dr A. Gouverneur, Dr G. Miremont, Pr A. Pariente, have no conflict of interest to disclose.
★★Pr A. Pariente is the coordinator of the French DRUGS-SAFE (DRUGS Systematized Assessment in real-liFe Environment) national platform of pharmacoepidemiology. This national platform is granted by the ANSM. This work is not part of the DRUGS-SAFE research programme (www.drugssafe.fr).
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