Association of levonorgestrel-releasing intrauterine device with gynecologic and breast cancers: a national cohort study in Sweden - 12/06/24

Doi : 10.1016/j.ajog.2024.05.011

Huan Yi, MD, PhD ^a,^b,^c,^⁎ , Naiqi Zhang, MD, PhD ^b, Jimiao Huang, MM ^a, Ying Zheng, MM ^d, Qiu hua Hong, BM ^a, Jan Sundquist, MD, PhD ^b,^e,^f,^g, Kristina Sundquist, MD, PhD ^b,^e,^f,^g, Xiangqin Zheng, MD ^a,^c,^⁎ , Jianguang Ji, MD, PhD ^a,^b,^⁎
^a 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
^b Department of Clinical Sciences Malmö, Center for Primary Health Care Research, Lund University, Malmo, Sweden
^c 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
^d Department of Obstetrics, Fuzhou Second Hospital, Fuzhou, Fujian, China
^e Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY
^f Department of Functional Pathology, Center for Community-Based Healthcare Research and Education (CoHRE), School of Medicine, Shimane University, Japan
^g University Clinic Primary Care Skåne, Region Skåne, Malmo, Sweden

^∗Corresponding authors: Huan Yi, MD, PhD.^∗∗Xiangqin Zheng, MD.^∗∗∗Jianguang Ji, MD, PhD.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Wednesday 12 June 2024

Abstract

Background

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.

Objective

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.

Study design

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.

Results

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.

Conclusion

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.

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Key words : breast cancer, family history, gynecologic cancer, levonorgestrel-releasing intrauterine device

Plan

Introduction

Methods

Data sources

Assessment of outcome

Assessment of covariates

Results in the context of what is known

Clinical implications

Research implications

Strengths and limitations

Conclusions

Data and materials availability statement

	H.Y., N.Z., J.H., and Y.Z. contributed equally to this work.
	The authors report no conflict of interest.
	This project was supported by Fujian Research and Training Grants for Young and Middle-Aged Leaders in Healthcare; Joint Funds for the Innovation of Science and Technology, Fujian Province (Grant number: 2021Y9169, 2021Y9180); Special Health Subidy of Fujian Provincial Finance Department (Grant number: 210020650502302); Fujian Provincial Natural Science Foundation (Grant number: 2023J011223); Youth and Middle-aged Training of Fujian Provincial Health Technology Project (Grant number: 2021GGB014) to H.Y. and MAS cancer to J.J.
	Cite this article as: Yi H, Zhang N, Huang J, et al. Association of levonorgestrel-releasing intrauterine device with gynecologic and breast cancers: a national cohort study in Sweden. Am J Obstet Gynecol 2024;XXX:XX–XX.