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Association of Levonorgestrel-Releasing Intrauterine Device with Gynecologic and Breast Cancers: National Cohort Study in Sweden

Yi, Huan LU ; Zhang, Naiqi LU ; Huang, Jimiao ; Zheng, Ying ; Hong, Qiu hua ; Sundquist, Jan LU ; Sundquist, Kristina LU ; Zheng, Xiangqin and Ji, Jianguang LU orcid (2024) In American Journal of Obstetrics and Gynecology 231(4). p.1-450
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 514719 women aged 18 to 50 years who have used LNG-IUD... (More)
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 514719 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 1544157 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 and 95% confidence intervals. 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 < 0.002), and 1.63 additional cases per 10,000 person-years.

Conclusions
The risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It's 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. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Obstetrics and Gynecology
volume
231
issue
4
pages
1 - 450
publisher
Elsevier
external identifiers
  • scopus:85196020191
  • pmid:38759709
ISSN
1097-6868
DOI
10.1016/j.ajog.2024.05.011
language
English
LU publication?
yes
id
0ad0fbbf-ff95-424c-b22f-b24f4e401e0b
date added to LUP
2024-05-16 19:43:34
date last changed
2024-10-14 11:56:55
@article{0ad0fbbf-ff95-424c-b22f-b24f4e401e0b,
  abstract     = {{Background<br/>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.<br/><br/>Objective<br/>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.<br/><br/>Study Design<br/>A total of 514719 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 1544157 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 and 95% confidence intervals. 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.<br/><br/>Results<br/>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 &lt; 0.002), and 1.63 additional cases per 10,000 person-years.<br/><br/>Conclusions<br/>The risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It's 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.}},
  author       = {{Yi, Huan and Zhang, Naiqi and Huang, Jimiao and Zheng, Ying and Hong, Qiu hua and Sundquist, Jan and Sundquist, Kristina and Zheng, Xiangqin and Ji, Jianguang}},
  issn         = {{1097-6868}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{4}},
  pages        = {{1--450}},
  publisher    = {{Elsevier}},
  series       = {{American Journal of Obstetrics and Gynecology}},
  title        = {{Association of Levonorgestrel-Releasing Intrauterine Device with Gynecologic and Breast Cancers: National Cohort Study in Sweden}},
  url          = {{http://dx.doi.org/10.1016/j.ajog.2024.05.011}},
  doi          = {{10.1016/j.ajog.2024.05.011}},
  volume       = {{231}},
  year         = {{2024}},
}