Background parenchymal enhancement in contrast-enhanced MR imaging suggests systemic effects of intrauterine contraceptive devices

Abstract

Objectives: Levonorgestrel-releasing intrauterine contraceptive devices (LNG-IUDs) are designed to exhibit only local hormonal effects. There is an ongoing debate on whether LNG-IUDs can have side effects similar to systemic hormonal medication. Benign background parenchymal enhancement (BPE) in dynamic contrast-enhanced (DCE) MRI has been established as a sensitive marker of hormonal stimulation of the breast. We investigated the association between LNG-IUD use and BPE in breast MRI to further explore possible systemic effects of LNG-IUDs.

Methods: Our hospital database was searched to identify premenopausal women without personal history of breast cancer, oophorectomy, and hormone replacement or antihormone therapy, who had undergone standardized DCE breast MRI at least twice, once with and without an LNG-IUD in place. To avoid confounding aging-related effects on BPE, half of included women had their first MRI without, the other half with, LNG-IUD in place. Degree of BPE was analyzed according to the ACR categories. Wilcoxon-matched-pairs signed-rank test was used to compare the distribution of ACR categories with vs. without LNG-IUD.

Results: Forty-eight women (mean age, 46 years) were included. In 24/48 women (50% [95% CI: 35.9-64.1%]), ACR categories did not change with vs. without LNG-IUDs. In 23/48 women (48% [33.9-62.1%]), the ACR category was higher with vs. without LNG-IUDs; in 1/48 (2% [0-6%]), the ACR category was lower with vs. without LNG-IUDs. The change of ACR category depending on the presence or absence of an LNG-IUD proved highly significant (p < 0.001).

Conclusion: The use of an LNG-IUD can be associated with increased BPE in breast MRI, providing further evidence that LNG-IUDs do have systemic effects.

Key points: • The use of levonorgestrel-releasing intrauterine contraceptive devices is associated with increased background parenchymal enhancement in breast MRI. • This suggests that hormonal effects of these devices are not only confined to the uterine cavity, but may be systemic. • Potential systemic effects of levonorgestrel-releasing intrauterine contraceptive devices should therefore be considered.

Keywords: Background parenchymal enhancement; Breast MRI; Contraception; Levonorgestrel; Levonorgestrel-releasing intrauterine device.

Fig. 1

Study design. The total study cohort consisted of 48 premenopausal women. Women underwent their first MRI study (left column) either with an IUD in place (group A, examination A1) or without an IUD in place (group B, examination B1). At the second MRI study (right column), women of group A had the MRI after IUD removal (examination A2); women of group B had the MRI after IUD placement (examination B2). The main comparison is on the respective levels of BPE in the MRI with vs. without LNG-IUD for each individual woman. In addition, a groupwise analysis of BPE in women with (A1 and B2) vs. without (A2 and B1) LNG-IUD was done. A1, first MRI examination of women of group A (with LNG-IUD in place); A2, second MRI examination of women of group A (without LNG-IUD in place); B1, first MRI examination of women of group B (without LNG-IUD in place); B2, second MRI examination of women of group B (with LNG-IUD in place)

Fig. 2

Flow chart of women examined in our institution between 2014 to 2020. LNG-IUD = levonorgestrel-releasing intrauterine contraceptive device, HRT = hormone replacement therapy

Fig. 3

Distribution of background parenchymal enhancement MR-ACR categories depending on the presence or absence of a levonorgestrel-releasing intrauterine contraceptive device (LNG-IUD) in the entire study cohort

Fig. 4

BPE on DCE-MRI in women with vs. without LNG-IUD. A.1 and A.2: a premenopausal woman undergoing MRI for screening because of dense breast tissue of group A. Maximum-intensity projection images (MIPs) of the first post-contrast subtracted images of the woman’s MRI (A.1) at age 44, with LNG-IUD (Mirena®) in place since 3 years, and (A.2) the same woman, now aged 47, after LNG-IUD removal. BPE was categorized as MR-ACR 3 in A.1 and MR-ACR 2 in A.2. B.1 and B.2: a premenopausal woman undergoing MRI for screening because of dense breast tissue of group B. Maximum-intensity projection images (MIPs) of the first post-contrast subtracted images of the woman’s MRI (B.1) at age 41, without LNG-IUD in place, and (B.2) the same woman, now aged 42, after LNG-IUD placement (Mirena®) 1.5 years ago. BPE was categorized as MR-ACR 2 in B.1 and MR-ACR 4 in B.2