Department of Gynecologic Oncology, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China; Department of Clinical Sciences Malmö, Center for Primary Health Care Research, Lund University, Malmo, Sweden; Fujian Province Key Clinical Specialty for Gynecology, Fujian Key Laboratory of Women and Children's Critical Diseases Research, National Key Gynecology Clinical Specialty Construction Institution of China, Fuzhou, Fujian, China.
Department of Clinical Sciences Malmö, Center for Primary Health Care Research, Lund University, Malmo, Sweden.
Am J Obstet Gynecol. 2024 Oct;231(4):450.e1-450.e12. doi: 10.1016/j.ajog.2024.05.011. Epub 2024 May 15.
The levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive.
We aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer.
A total of 514,719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1,544,157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users as well as for their matched comparisons and ended at the date of diagnosis of gynecologic and breast cancers, date of death from any cause, and the end of the study period, whichever came first. The Cox proportional hazard model with a competing risk analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, while multiplicative interaction was calculated by including a product term in the regression model.
The use of LNG-IUD was associated with a 13% higher risk of breast cancer (adjusted HR, 1.13; 95% CI, 1.10-1.17), a 33% lower risk of endometrial cancer (adjusted HR, 0.67; 95% CI, 0.56-0.80), a 14% lower risk of ovarian cancer (adjusted HR, 0.86; 95% CI, 0.75-0.99), and a 9% reduced risk of cervical cancer (adjusted HR, 0.91; 95% CI, 0.84-0.99) compared to women who did not use LNG-IUD. A significant additive interaction between LNG-IUD use and family history of cancer was observed in breast cancer, indicating a relative 19% excess risk for interaction (P<.002), and 1.63 additional cases per 10,000 person-years.
The risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It is important to note that the observed effect is small for breast cancer and the results are limited by the observational study design. Clinical recommendations regarding the use of LNG-IUD should carefully weigh its potential benefits and risks. Close monitoring is advisable for the potential development of breast cancer, particularly among women with a family history of breast cancer.
左炔诺孕酮宫内节育器（LNG-IUD）被广泛用于治疗月经过多、痛经和避孕。然而，LNG-IUD 的使用与特定部位妇科和乳腺癌风险之间的关联仍存在争议。
我们旨在通过调查 LNG-IUD 的使用是否与特定部位妇科和乳腺癌的显著风险相关来解决这一知识空白。这将通过访问全国性的瑞典登记处来实现，并考虑癌症家族史的影响和潜在相互作用。
从瑞典处方药物登记处中确定了 514719 名年龄在 18 至 50 岁之间的女性，她们在 2005 年 7 月至 2018 年 12 月期间使用了 LNG-IUD，并随机与未使用 LNG-IUD 的 1544157 名女性进行了 1:3 的匹配。计算了倾向评分并在使用 LNG-IUD 的女性和匹配的对照组之间进行了匹配。随访期从用户首次使用 LNG-IUD 以及他们的匹配对照开始，截止于妇科和乳腺癌的诊断日期、任何原因导致的死亡日期或研究期结束日期，以先到者为准。使用竞争风险分析的 Cox 比例风险模型计算了危险比（HR）和 95%置信区间（CI）。加性交互作用通过交互作用的相对超额风险来计算，而乘法交互作用通过在回归模型中包含乘积项来计算。
与未使用 LNG-IUD 的女性相比，使用 LNG-IUD 与乳腺癌风险增加 13%（调整后的 HR，1.13；95%CI，1.10-1.17）、子宫内膜癌风险降低 33%（调整后的 HR，0.67；95%CI，0.56-0.80）、卵巢癌风险降低 14%（调整后的 HR，0.86；95%CI，0.75-0.99）和宫颈癌风险降低 9%（调整后的 HR，0.91；95%CI，0.84-0.99）相关。在乳腺癌中观察到 LNG-IUD 使用与癌症家族史之间存在显著的加性交互作用，表明交互作用的相对超额风险为 19%（P<.002），每 10000 人年增加 1.63 例。
LNG-IUD 使用者的妇科和乳腺癌风险呈现出特定部位的效应。值得注意的是，乳腺癌的观察到的效果较小，且结果受到观察性研究设计的限制。关于 LNG-IUD 使用的临床建议应仔细权衡其潜在的益处和风险。应密切监测乳腺癌的潜在发展，特别是在有乳腺癌家族史的女性中。
