MRI Monitor: IUDs Can Have Systemic Effects
By Beth W. Orenstein
Radiology Today
Vol. 23 No. 2 P. 8

The background parenchymal enhancement (BPE) on dynamic contrast-enhanced breast MRI is a well-known marker for hormone levels. Researchers in Aachen, North Rhine–Westphalia, Germany, used this marker to demonstrate that women with intrauterine devices (IUDs) that release levonorgestrel, a progestin, can experience systemic effects.

“Manufacturers claim that IUDs have a purely local effect on the uterus,” says Luisa Huck, MD, a radiology resident at Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University and lead author of a study presented at RSNA 2021. “However, our results support the reports of women with IUDs who claim to have systemic side effects.” Side effects reported by women with IUDs include depression, headaches, sleep disorders, and panic attacks.

The IUD manufacturers claim that because their IUDs release only small amounts of hormone directly into the uterus, the amount in the bloodstream is low and less than with other hormonal contraceptive methods. In theory, this limited area of release should mean the side effects are confined to the region around the IUD.

Knowing that breast MR is a very sensitive measure of circulating hormones, Huck and colleagues, including senior author of the study Christiane Kuhl, MD, chief of the radiology department at RWTH Aachen University, searched their hospital database for premenopausal women who had undergone breast cancer screening with MRI between January 2014 and July 2020 at least twice. They specifically searched for women who had one scan before an IUD was placed and one scan at least four weeks after they had an IUD placed or removed. None of the women included in the study had a history of breast cancer or hormone or antihormone intake.

Their goal was to trace a change in systemic hormone levels by comparing the level of contrast enhancement in the same women with and without the IUD in place, Huck says.

Before-and-After Scans
Scans from a total of 48 women with an average age of 45 fit their criteria and were studied. The two scans the women had were a median 27 months apart. One-half of the women in the study underwent the first breast MRI exam before IUD placement and the second with the IUD in place. The remainder of participants had their first MRI with IUD placement and the second MRI after IUD removal. This enabled the researchers to avoid age-related effects on BPE that might affect interpretation of the results.

Their results: 23 of the women in the study had background enhancement that was higher on their scans with the IUD than on their scans without the IUD (p<0.001); 24 women had no change in BPE with or without an IUD; and one woman had lower BPE with an IUD than without it.

The results, Huck says, indicate that the use of IUD leads to hormonal stimulation of the breast that is detectable by MRI. “This means there are hormone effects caused by IUD that occur far away from the uterus,” she says. Obviously, she adds, “IUDs do not have a purely local effect on the uterus, but on the entire body. And it is plausible that IUDs can have side effects similar to that of other hormonal treatments.”

Stamatia Destounis, MD, FACR, FSBI, FAIUM, who is a partner/owner at Elizabeth Wende Breast Care in Rochester, New York; chief of the ACR’s Breast Imaging Commission; and chair of the ACR Breast MRI Accreditation Committee, agrees with the researchers’ conclusion. “The interesting thing about the enhancement is that it should not happen if the hormone released by the IUD is local to the uterus only,” Destounis says. “But this study reveals that there were parenchymal changes with enhancement in some of the women that had an IUD vs not.”

As to the question of why one-half of the participants showed no variation in BPE, Destounis, who is also a member of Radiology Today’s Editorial Advisory Board, suggests that the IUD may not be “a direct cause and effect. It may be variable in women and not exactly have the same presentation in everyone. Some women may have no changes, some subtle, some pronounced,” Destounis says.

Enhancement on MRI can happen with a woman’s monthly cyclical variation, Destounis adds, “so I don’t believe this should be considered worrisome, but it may affect interpretation of the MRI and thus it is important for the radiologist to be aware.”

Huck agrees that the increased enhancement “also has implications for the diagnostic accuracy of breast MRI in women using hormonal IUDs.”

Shaping the Discussion
Enhancements on breast MRI sometimes can lead to additional imaging studies or biopsies. Given the results of this study, should women be asked whether they have IUDs before undergoing breast MRI? “Most facilities do ask if a woman has had a hysterectomy, if she is on estrogen replacement therapy, or if she is on an oral or other type of contraceptive,” Destounis says. “If facilities are not asking these specific questions, the information may be missed. So, it is important for centers performing breast MRI to evaluate their questionnaires and make certain they are including specific questions regarding hormonal replacement and also IUDs.”

Destounis adds that this study should be followed up with additional clinical investigation. “The authors’ findings suggest that the radiologist interpreting the MRI should be aware if the patient has an IUD in place, as there may be some enhancement that may be different than prior years if the patient did not have the IUD previously,” she says. “This is an area that should be researched/investigated carefully, as IUDs are very prevalent and helpful in our society and research specific to whether these changes are harmful in any way should be done.”

Would it be helpful to test hormonal levels in patients with elevated BPE? Yes, Destounis says. “It may reveal what hormone levels are elevated in women that respond with higher background enhancement and also reveal what level of hormone will elicit what response for these women.” The relationship of hormone levels and enhancement on MRI may not be linear, she adds. “This topic is certainly very interesting, and more information will have to be obtained along with additional investigation in varied populations to see whether the data collected by the authors are similar in other settings.”

Regular Screening With MRI?
Destounis also believes that some women who have IUDs could benefit from regular screening with MRI. “Certainly, the benefits of identifying a mass on MRI in high-risk women for breast cancer, secondary to genetic mutation and family history or personal history of breast cancer, are very important, and women should have a breast MRI given its high sensitivity to find occult breast cancer that may hide in dense breast tissue on mammography and may not be identifiable on ultrasound.”

Multiple studies also have shown that elevated BPE levels, measured qualitatively or quantitatively, are linked to a greater risk of developing breast cancer, according to a study published in January 2020 in the Journal of Magnetic Resonance Imaging.

According to the Centers for Disease Control and Prevention, a little more than 10% of women in the United States aged 15 to 49 use an IUD or contraceptive implant. Of the FDA-approved IUDs available in the United States, four (Mirena, Liletta, Skyla, and Kyleena) are hormonal IUDs that release very small amounts of levonorgestrel (a fifth, Paragard, is a copper IUD). Of the women in the study, 98 had the Mirena levonorgestrel-releasing IUD.

Even with this study, Huck would tell women that IUDs appear to be a very safe means of contraception and are generally well tolerated. She adds that women who experience so-far unexplainable side effects should talk to their doctor “and consider using other types of contraception.”

— Beth W. Orenstein, of Northampton, Pennsylvania, is a freelance medical writer and regular contributor to Radiology Today.