Archives of Gynecology and Obstetrics

, Volume 299, Issue 6, pp 1597–1605 | Cite as

Disease activity and thromboembolic events in women with systemic lupus erythematosus with and without anti-phospholipid syndrome: users of the 52-mg levonorgestrel-releasing intrauterine system

  • Rafaella C. Rebelo
  • Estephania Pignaton
  • M. Valeria Bahamondes
  • Lilian T. L. Costallat
  • Simone Appenzeller
  • Luis Bahamondes
  • Arlete FernandesEmail author
General Gynecology



The disease status and thromboembolic events in women with systemic lupus erythematosus (SLE), with and without anti-phospholipid syndrome (APS), were evaluated before and after placement of the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS).


A retrospective cohort study, with review of medical records of SLE women, who received an LNG-IUS placement between January 2007 and December 2016, carried out at the University of Campinas Medical School, Brazil. The outcomes included the disease activity (SLEDAI-2K) and damage index scores (SLICC/ACR-DI) presented for each year of device use, as well as venous/arterial thrombotic events, insertion up to a median of 5 years. The author’s used χ2, Fisher’s exact and the Mann–Whitney tests for analysis and generalized estimating equations for score comparison.


The study evaluated 46 women with SLE, 18 with and 28 without APS; the mean age (± standard deviation [SD]) was 31.8 (SD ± 8.3) years old. The length of follow-up after LNG-IUS placement was 5.6 (SD ± 2.7) and 4.1 (SD ± 2.3) years for the groups with and without APS, respectively. Comparison of the groups found that the SLEDAI and SLICC mean scores were low for both at baseline, without variations through the follow-up. After LNG-IUS placement, two women presented three thrombotic arterial events, and one of them died from causes unrelated to LNG-IUS use.


Our results, although restricted, provide information to policymakers and health professionals that the use of a 52 mg LNG-IUS over a 5-year median did not increase disease activity or damage index scores among women with SLE, with and without APS.


Systemic lupus erythematosus Antiphospholipid syndrome Levonorgestrel-releasing intrauterine system Arterial and venous thrombotic events 


Author contributions

RCR protocol/project development and data collection. EP protocol/project development and data collection. MVB protocol/project development and data collection. LTLC protocol/project development and Manuscript writing/editing. SA protocol/project development. LB manuscript writing/editing and revision. AF protocol/project development and manuscript writing/editing and revision.


The original study was funded by the Brazilian National Research Council (CNPq) and the São Paulo Foundation for the Support of Research (Fundação de Amparo a Pesquisa do Estado de São Paulo—FAPESP). The sponsors played no role in the study design, in the collection, analysis or interpretation of data, in writing the report or in the decision to submit the article for publication. The authors claim they do not have a financial relationship with the organizations that sponsored the research. They claim that they have had full control of all primary data and agree to allow the Journal to review their data if requested.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest. The authors alone are responsible for the content and writing of the paper. LB received honorarium to be a member of an advisory board and has been an invited speaker at scientific meetings for Bayer Healthcare Pharmaceuticals. He is a member of the ICA Foundation without remuneration. The LNG-IUS were donated by the International Contraceptive Access (ICA) Foundation, Turku, Finland, under an unrestricted grant.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Since it was a retrospective study with a review of medical records, the waiver of signature in the consent form was requested and approved in the evaluation of the project.


  1. 1.
    Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277CrossRefGoogle Scholar
  2. 2.
    Williamson RA, Karp LE (1981) Azathioprine teratogenicity: review of the literature and case report. Obstet Gynecol 58:247–250Google Scholar
  3. 3.
    Ossandon A, Cassarà EA, Priori R, Valesini G (2002) Thalidomide: focus on its employment in rheumatologic diseases. Clin Exp Rheumatol 20:709–718Google Scholar
  4. 4.
    Rengasamy P (2017) Congenital malformations attributed to prenatal exposure to cyclophosphamide. Anticancer Agents Med Chem 17:1211–1227CrossRefGoogle Scholar
  5. 5.
    Vianna JL, Haga HJ, Tripathi P, Cervera R, Khamashta MA, Hughes GR (1992) Reassessing the status of antiphospholipid syndrome in systemic lupus erythematosus. Ann Rheum Dis 51:160–161CrossRefGoogle Scholar
  6. 6.
    Gould T, Tikly M, Asherson R, Loizou S, Singh S (2006) Prevalence and clinical correlates of anti-phospholipid antibodies in South Africans with systemic lupus erythematosus. Scand J Rheumatol 35:29–34CrossRefGoogle Scholar
  7. 7.
    Mok CC, Chan PT, Ho LY, Yu KL, To CH (2013) Prevalence of the antiphospholipid syndrome and its effect on survival in 679 Chinese patients with systemic lupus erythematosus: a cohort study. Medicine (Baltim) 92:217–222CrossRefGoogle Scholar
  8. 8.
    Franco JS, Molano-González N, Rodríguez-Jiménez M, Acosta-Ampudia Y, Mantilla RD, Amaya-Amaya J et al (2014) The coexistence of antiphospholipid syndrome and systemic lupus erythematosus in Colombians. PLoS One 24(9):e110242CrossRefGoogle Scholar
  9. 9.
    Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306CrossRefGoogle Scholar
  10. 10.
    Garcia D, Erkan D (2018) Diagnosis and management of the antiphospholipid syndrome. N Engl J Med 378:2010–2021CrossRefGoogle Scholar
  11. 11.
    Pons-Estel GJ, Andreoli L, Scanzi F, Cervera R, Tincani A (2017) The antiphospholipid syndrome in patients with systemic lupus erythematosus. J Autoimmun 76:10–20CrossRefGoogle Scholar
  12. 12.
    Griffiths B, Mosca M, Gordon C (2005) Assessment of patients with systemic lupus erythematosus and the use of lupus disease activity indices. Best Pract Res Clin Rheumatol 19:685–708CrossRefGoogle Scholar
  13. 13.
    Sánchez-Guerrero J, Uribe AG, Jiménez-Santana L, Mestanza-Peralta M, Lara-Reyes P, Seuc AH et al (2005) A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med 353:2539–2549CrossRefGoogle Scholar
  14. 14.
    Petri M, Kim MY, Kalunian KC, Grossman J, Hahn BH, Sammaritano LR et al (2005) Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 353:2550–2558CrossRefGoogle Scholar
  15. 15.
    Andreoli L, Bertsias GK, Agmon-Levin N, Brown S, Cervera R, Costedoat-Chalumeau N et al (2017) EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis 76:476–485CrossRefGoogle Scholar
  16. 16.
    Conard J, Plu-Bureau G, Bahi N, Horellou MH, Pelissier C, Thalabard JC (2004) Progestogen-only contraception in women at high risk of venous thromboembolism. Contraception 70:437–441CrossRefGoogle Scholar
  17. 17.
    Blanco-Molina MA, Lozano M, Cano A, Cristobal I, Pallardo LP, Lete I (2012) Progestin-only contraception and venous thromboembolism. Thromb Res 129:e257–e262CrossRefGoogle Scholar
  18. 18.
    Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C (2009) Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ 339:b2890CrossRefGoogle Scholar
  19. 19.
    Tepper NK, Whiteman MK, Marchbanks PA, James AH, Curtis KM (2016) Progestin only contraception and thromboembolism: a systematic review. Contraception 94:678–700CrossRefGoogle Scholar
  20. 20.
    World Health Organization (2015) Medical eligibility criteria for contraceptive use—5th ed. Switzerland. Accessed 01 June 2018
  21. 21.
    Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640CrossRefGoogle Scholar
  22. 22.
    Romero-Diaz J, Isenberg D, Ramsey-Goldman R (2011) Measures of adult systemic lupus erythematosus: updated version of British Isles Lupus Assessment Group (BILAG 2004), European Consensus Lupus Activity Measurements (ECLAM), Systemic Lupus Activity Measure, Revised (SLAM-R), Systemic Lupus Activity Questionnaire for Population Studies (SLAQ), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Arthritis Care Res (Hoboken) 63(Suppl 11):S37–S46CrossRefGoogle Scholar
  23. 23.
    World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception (1998) Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. Results of an international, multicenter, case-control study. Contraception 57(5):315–324CrossRefGoogle Scholar
  24. 24.
    van Hylckama Vlieg A, Helmerhorst FM, Rosendaal FR (2010) The risk of deep venous thrombosis associated with injectable depot-medroxyprogesterone acetate contraceptives or a levonorgestrel intrauterine device. Arterioscler Thromb Vasc Biol 30:2297–2300CrossRefGoogle Scholar
  25. 25.
    Mantha S, Karp R, Raghavan V, Terrin N, Bauer KA, Zwicker JI (2012) Assessing the risk of venous thromboembolic events in women taking progestin only contraception: a meta-analysis. BMJ 345:e4944CrossRefGoogle Scholar
  26. 26.
    Lidegaard Ø, Løkkegaard E, Jensen A, Skovlund CW, Keiding N (2012) Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med 366:2257–2266CrossRefGoogle Scholar
  27. 27.
    Hinojosa-Azaola A, Romero-Diaz J, Vargas-Ruiz AG, Nuñez-Alvarez CA, Cicero-Casarrubias A, Ocampo-Torres MC et al (2016) Venous and arterial thrombotic events in systemic lupus erythematosus. J Rheumatol 43:576–586CrossRefGoogle Scholar
  28. 28.
    Choojitarom K, Verasertniyom O, Totemchokchyakarn K, Nantiruj K, Sumethkul V, Janwityanujit S (2008) Lupus nephritis and Raynaud’s phenomenon are significant risk factors for vascular thrombosis in SLE patients with positive antiphospholipid antibodies. Clin Rheumatol 27:345–351CrossRefGoogle Scholar
  29. 29.
    Urbanus R, Siegerink B, Roest M, Rosendaal F, de Groot P, Algra A (2009) Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study. Lancet Neurol 8:998–1005CrossRefGoogle Scholar
  30. 30.
    Matyja-Bednarczyk A, Swadźba J, Iwaniec T, Sanak M, Dziedzina S, Ćmiel A et al (2014) Risk factors for arterial thrombosis in antiphospholipid syndrome. Thromb Res 133:173–176CrossRefGoogle Scholar
  31. 31.
    Kaiser R, Tang LF, Taylor KE, Sterba K, Nititham J, Brown EE et al (2014) A polymorphism in TLR2 is associated with arterial thrombosis in a multiethnic population of patients with systemic lupus erythematosus. Arthritis Rheumatol 66:1882–1887CrossRefGoogle Scholar
  32. 32.
    Kuhl H (1996) Effects of progestogens on haemostasis. Maturitas 24:1–19CrossRefGoogle Scholar
  33. 33.
    Nilsson CG, Haukkamaa M, Vierola H, Luukkainen T (1982) Tissue concentrations of levonorgestrel in women using a levonorgestrel-releasing IUD. Clin Endocrinol (Oxf) 17(6):529–536CrossRefGoogle Scholar
  34. 34.
    Seeber B, Ziehr SC, Gschlieβer A, Moser C, Mattle V, Seger C et al (2012) Quantitative levonorgestrel plasma level measurements in patients with regular and prolonged use of the levonorgestrel-releasing intrauterine system. Contraception 86:345–349CrossRefGoogle Scholar
  35. 35.
    Brito MB, Casqueiro JS, Alves FSS, Lopes JB, Alves RDMS, Santiago M (2018) Low prevalence of contraceptive use among Brazilian women of reproductive age with systemic lupus erythematosus. J Obstet Gynaecol 19:1–4Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Family Planning Clinic, Department of Obstetrics and Gynaecology, School of Medical SciencesUniversity of Campinas (UNICAMP)CampinasBrazil
  2. 2.Rheumatology Division, Department of Clinical Medicine, School of Medical SciencesUniversity of Campinas (UNICAMP)CampinasBrazil

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