{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T10:03:24Z","timestamp":1784801004890,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: The levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used as a long-acting reversible contraceptive and as a therapeutic option for heavy menstrual bleeding, endometriosis, adenomyosis, and endometrial hyperplasia. Although its predominant effect is local, systemic levonorgestrel exposure has raised questions regarding its potential influence on cancer risk. This review aims to summarise and critically appraise the available evidence on the association between LNG-IUD use and gynaecologic, breast, and selected non-gynaecologic malignancies (including colorectal, lung, pancreatic, gastric, thyroid, skin [melanoma], and haematological cancers). Methods: A structured narrative review was developed by a multidisciplinary expert group affiliated with the European Society of Gynaecological Oncology (ESGO) and the European Society for Gynaecological Endoscopy (ESGE). PubMed\/MEDLINE, Embase, and Scopus were searched in December 2024 without publication-date restrictions. We critically appraised epidemiological and clinical evidence on LNG-IUD use and breast, endometrial, ovarian, cervical, and selected non-gynaecologic cancer risks, prioritising population-based cohorts, registry-based studies, case\u2013control studies, systematic reviews, and meta-analyses. Results: The strongest and most consistent evidence supports a substantial reduction in endometrial cancer risk among LNG-IUD users, with a possible protective association also suggested for ovarian cancer. Available data do not indicate a clear increase in cervical cancer, CIN3+, or invasive cervical disease. In contrast, evidence for breast cancer remains heterogeneous, with some registry-based studies suggesting a modest relative increase and other cohort or case\u2013control studies showing no significant association. Evidence regarding non-gynaecologic cancers remains limited and inconclusive. Conclusions: Overall, current evidence suggests that the LNG-IUD has a favourable oncological safety profile, with the strongest evidence supporting a significant reduction in endometrial cancer risk and a potential protective effect against ovarian cancer. There is no evidence pointing to increased risk of cervical cancer. However, results related to breast cancer are mixed, and a slight risk increase cannot be ruled out; thus, counselling should be personalised based on the indication, menopausal status, duration of use, and individual breast cancer risk.<\/jats:p>","DOI":"10.3390\/cancers18152374","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:11:26Z","timestamp":1784797886000},"page":"2374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cancer Risk Profile of the Levonorgestrel-Releasing Intrauterine Device: A Narrative Review"],"prefix":"10.3390","volume":"18","author":[{"given":"Utku","family":"Akg\u00f6r","sequence":"first","affiliation":[{"name":"Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Faculty of Medicine, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilal Esat","family":"Temiz","sequence":"additional","affiliation":[{"name":"Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Faculty of Medicine, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan Volkan","family":"Ege","sequence":"additional","affiliation":[{"name":"Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Faculty of Medicine, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Burney","family":"Ellis","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Bowden","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kyrgiou","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7807-5908","authenticated-orcid":false,"given":"Marc","family":"Arbyn","sequence":"additional","affiliation":[{"name":"Belgian Cancer Centre, Sciensano, 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1573-3114","authenticated-orcid":false,"given":"Mario","family":"Preti","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5357-4708","authenticated-orcid":false,"given":"Kimon","family":"Chatzistamatiou","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynaecology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6598-0896","authenticated-orcid":false,"given":"Zoia","family":"Razumova","sequence":"additional","affiliation":[{"name":"Karolinska Institute, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3513-7192","authenticated-orcid":false,"given":"Vesna","family":"Kesic","sequence":"additional","affiliation":[{"name":"Clinic for Obstetrics and Gynaecology, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1727-904X","authenticated-orcid":false,"given":"Nicol\u00f2","family":"Bizzarri","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Unit, Department of Woman, Child and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Gassama","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Faculty of Medicine, Pharmacy and Odonto-Stomatology, Cheikh Anta Diop University (UCAD), Dakar-Fann P.O. Box 5005, Senegal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reda","family":"Hemida","sequence":"additional","affiliation":[{"name":"Mansoura Gynecologic Oncology Unit (MGOU), Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagham","family":"Ibraheem","sequence":"additional","affiliation":[{"name":"Baghdad Teaching Hospital, Al-Kindi Medical College, University of Baghdad, Jadirya, Baghdad P.O. Box 47188, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7613-8354","authenticated-orcid":false,"given":"Houssein","family":"El Hajj","sequence":"additional","affiliation":[{"name":"Gustave Roussy Cancer Campus, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepali","family":"Raina","sequence":"additional","affiliation":[{"name":"Fortis Memorial Research Institute (FMRI), Gurugram 122002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Collinet","sequence":"additional","affiliation":[{"name":"H\u00f4pital Priv\u00e9 Le Bois\u2014Ramsay Sant\u00e9, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8628-6745","authenticated-orcid":false,"given":"Bernhard","family":"Kr\u00e4mer","sequence":"additional","affiliation":[{"name":"Department for Women\u2019s Health, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Gultekin","sequence":"additional","affiliation":[{"name":"Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Faculty of Medicine, Hacettepe University, Ankara 06230, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3109\/07853899009147248","article-title":"Levonorgestrel-releasing intrauterine device","volume":"22","author":"Luukkainen","year":"1990","journal-title":"Ann. 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