Vice-Chair, Associate Clinical Professor, Department of Obstetrics and Gynecology

Ilana Cass, MD

As ob/gyns, we care for patients with a variety of gynecologic and reproductive health issues that can be emotionally charged and intensely private. Although gynecologic health issues are medical issues as are headaches or sprained ankles, the extent to which individuals want to talk openly about them varies. In our offices, patients share their fears, their pains, and their hopes, and discuss their sexuality, their gender identity, and their sexual behaviors. We talk with preteens about puberty, with teens about their periods, with women who are excited to be pregnant, and with those who are not. We talk to women who have never told anyone about a past sexual assault. We talk with women who are facing infertility or the need for a hysterectomy. Our patients know we will listen to and treat them with dignity and provide accurate health education that enables them to be a partner in their health care decisions.

Three recent pieces of legislation highlight a threat to the physician-patient relationship. The proposal of laws that interfere with this complex and intimate relationship is a step too far. These pieces of legislation illustrate this overreach by the state: dictating medical care for transgender adolescents (Arkansas and 18 other states),

 mandating medically inaccurate information about abortion (18 states),

 and requiring resuscitation for newborns with fatal diagnoses (New Hampshire).

As Frank Bruni pointed out in his recent 

 op-ed column, politicians are currently demonizing trans people in a new culture war, similar to the way in which they vilified gays and lesbians, charging that gay marriages would somehow undermine straight marriages.

 Politicians, including former President Donald Trump, assert that trans equality would “destroy women’s sports.”

 This is a political strategy that ignores the realities of the patients in our offices. It ignores the transgender individual who has found puberty blockers to be immensely helpful or the trans persons who had previously been suicidal when attempting to fit in to a gender-binary world. It ignores the parents who have wrestled with their child’s affirmed gender identity, done extensive research and reading about the issue, and who love their child and support therapy and potentially medication to help alleviate their child’s gender dysphoria. It ignores our medical judgment and recommendations after we have listened to the patient and their parents. It ignores the expertise of our colleagues in endocrinology, psychology, adolescent medicine, adolescent gynecology, urology, and social work who work with transgender youth. As Bruni describes, these lawmakers are stunningly arrogant, and are “getting between physicians and patients.”

As many state legislatures across the U.S. introduce or have in process bills that could directly impact the physician-patient relationship and how treatments are administered, several professional organizations issued position statements. 

In its statement, the North American Society of Adolescent and Pediatric Gynecology stated that it has nearly 470 members consisting of physicians, advanced practice providers, nurses, and professional health care trainees. “Our mission is to provide multidisciplinary leadership in education, research and gynecologic care to improve the reproductive health of all youth, inclusive of children and adolescents who are gender diverse. 

We advocate for the provision of unrestricted, unbiased and evidence-based practice of pediatric and adolescent gynecology. We stand with national medical organizations supporting comprehensive care of adolescents and the confidential relationship between patients and their physicians.

 We support the positions that `physicians must be able to practice medicine that is informed by their years of medical education, training, experience, and the available evidence, freely and without threat of punishment. Patients, their families and caretakers in partnership with their physicians, not policymakers, should be the ones to make decisions about what care is best for them.’”

The other organizations included the American College of Obstetricians and Gynecologists; the American Academy of Family Physicians; the American Academy of Pediatrics; the American Psychiatric Association; and the American Osteopathic Association.

Frontline physicians oppose legislation that interferes in or penalizes patient care. American Academy of Pediatrics. April 2, 2021. Accessed April 26, 2021.

https://services.aap.org/en/news-room/news-releases/aap/2021/frontline-physicians-oppose-legislation-that-interferes-in-or-penalizes-patient-care/

It is not controversial to agree that our obligation as physicians is to care for our patients in a way that best meets their needs. We should also agree that legislatures do not have a role in dictating specifics of medical care. The Coalition to Protect the Patient-Provider Relationship is comprised of nonpartisan, nonprofit organizations united in the “opposition to inappropriate interference in the relationship between a patient and health care provider.”6 Member organizations include the American College of Obstetricians and Gynecologists (ACOG), American Academy of Family Physicians, American Academy of Pediatrics, American College of Physicians, American Medical Association, American Medical Student Association, American Medical Women’s Association, American Nurses Association, American Osteopathic Association, American Public Health Association. The coalition states that “patients deserve accurate information, high-quality care, and the treatment options that best meet their needs. Physicians and other health care providers should be able to follow the best medical science and training based on available evidence, and adhere to their ethical obligations.”

It’s not just in areas of women’s health that we must protect that relationship. Other health and safety issues for which politicians are passing laws that stand between us and our patients include gun safety and environmental hazards. Resources for clinicians include a report, “Politics in the Exam Room: A Growing Threat,” by the National Partnership for Women & Families, National Physicians Alliance, Natural Resources Defense Council, and Giffords Law Center to Prevent Gun Violence.

According to ACOG’s policy statement on legislative interference with patient care, medical decisions, and the patient-physician relationship, “laws should not interfere with the ability of physicians to determine appropriate treatment options and have open, honest, and confidential communications with their patients. Nor should laws interfere with the patient’s right to be counseled by a physician according to the best currently available medical evidence and the physician’s professional medical judgment. ACOG strongly opposes any governmental interference that threatens communications between patients and their physicians or causes a physician to compromise his or her medical judgment about what information or treatment is in the best interest of the patient.”

When state legislators try to come between our patients and us, we must speak out strongly. We must not let politics trump science or interfere with our hallowed patient relationships. Our patients must be able to rely upon us to provide appropriate and confidential care, based on science and our medical judgment. 

Legislative tracker: anti-transgender medical care bans

. Freedom for All Americans. Accessed April 13, 2021. 

https://freedomforallamericans.org/legislative-tracker/medical-care-bans/

2.Cox C. As Arkansas bans treatments for transgender youth, 15 other states consider similar bills. 

. April 8, 2021. Accessed April 13, 2021. https://www.usatoday.com/story/news/politics/2021/04/08/states-consider-bills-medical-treatments-transgender-youth/7129101002/

3.An overview of abortion laws. Guttmacher Institute. Updated April 1, 2021. Accessed April 11, 2021. https://www.guttmacher.org/state-policy/explore/overview-abortion-laws

4.Bruni F. Republicans find a cruel new culture war. 

. April 10, 2021. Accessed April 11, 2021. https://www.nytimes.com/2021/04/10/opinion/sunday/transgender-rights-republicans-arkansas.html

5.Ennis D. What Donald Trump’s transphobia really means for women’s sports. 

. February 28, 2021. Accessed April 13, 2021. https://www.forbes.com/sites/dawnstaceyennis/2021/02/28/what-donald-trumps-transphobia-really-means-for-womens-sports/?sh=3fac76545e66

6.About the coalition. Coalition to Protect the Patient-Provider Relationship. Accessed April 13, 2021. 

7.Politics in the exam room: a growing threat. National Partnership for Women & Families. October 2015. Accessed April 13, 2021. https://www.nationalpartnership.org/our-work/resources/repro/politics-in-the-exam-room-a-growing-threat.pdf

8.Legislative interference with patient care, medical decisions, and the patient-physician relationship. ACOG. Updated July 2019. Accessed April 13, 2021. 

https://www.acog.org/clinical-information/policy-and-position-statements/statements-of-policy/2019

Articles

Three recent pieces of legislation highlight a threat to the physician-patient relationship.


Keeping Politicians Out of the Exam Room

Slideshows

These ten images can help ob/gyns recognize the additional information GBCA administration provides in MRIs.

The value of GBCA in MRI images

Gadolinium-based intravenous contrast agents (GBCA) provide additional information based on signal intensity changes after GBCA administration. 

8 examples of how GBCA improves MRI

Magnetic resonance imaging (MRI) uses magnetic fields to provide detailed anatomic images that reflect distribution and magnetic properties of tissues (specifically of hydrogen nuclei in water and fat) to aid in diagnosis of many pathologic conditions. Gadolinium-based intravenous contrast agents (GBCA) provide additional information based on signal intensity changes after GBCA administration. GBCA are used in approximately 45% of MRI exams in the United States. In the 30 years since the first GBCA was introduced into clinical practice, almost a half billion enhanced MRI studies have been performed worldwide. In the field of gynecology, MRI is widely used to enhance detection of early breast cancers in women at elevated risk, or to better delineate complex pelvic anatomy in the setting of prior pelvic surgery, severe endometriosis, distorting fibroids, cervical, uterine cancer or ovarian cancer.

A recent concern with use of GBCA surfaced in 2014, when the link between permanent high T1 signal in the dentate nucleus and globus pallidus of the brain and repeated prior GBCA exposure was identified.

 Post-mortem analysis of these deep brain structures confirmed that gadolinium deposition in the brain of patients who had GBCA-enhanced MRI of any part of the body. Specifically, higher signal intensities were seen in patients who had undergone at least six contrast-enhanced MRI examinations compared to patients who had undergone only non-contrast MRI. Case reports in children noted the same pattern of gadolinium deposition as that seen in adult patients following GBCA.

Industry-sponsored studies in rats serially exposed to GBCA found progressively higher signal intensity on imaging, which correlated with post-mortem gadolinium concentrations in the brain.

 Notably, at the time of this writing, no human or animal data have shown any association between GBCA exposure and neurologic toxicity or neurological symptoms related to gadolinium deposition in the dentate nucleus of globus pallidus.

Ob/gyns need to be aware of the current data about gadolinium-based contrast and the potential implications of its use when they order MRI for their patients.


	In response to the reports of gadolinium deposition in the brain of GBCA-exposed individuals, the US Food and Drug Administration (

) required a new class warning and other safety measures for all GBCA for MRI in December 2017. Updates to GBCA labeling in May 2018 stated that GBCA was safe and should be used when medically necessary, and directed MRI centers to make educational information available to every outpatient the first time they receive GBCA.

 includes risk of gadolinium retention associated with the two types of GBCA (linear and macrocyclic) and indicates that linear GBCA appears to result in higher retention for longer periods of time than macrocyclic GBCA. Providers are encouraged to consider patient characteristics that may result in increased risk of gadolinium retention, and to minimize closely spaced or multiple GBCA MRI. 

Gulani and colleagues, on behalf of the International Society for Magnetic Resonance in Medicine (

) summarized the evidence and offered guidelines to clinicians in 

 They highlighted incomplete understanding of the clinical implications and mechanisms that drive gadolinium deposition, and discordant data comparing different types of gadolinium. The authors advised health care professionals to use caution when administering GBCA and to carefully document 

a specific GBCA is given to a patient. They did not endorse macrocyclic over linear GBCA, and suggested that patient and clinical factors in addition to pharmacokinetics of the available agents should guide selection of the best GBCA. The American College of Radiology independently endorsed the same recommendation.

 Finally, the ISMRM Summary urged ongoing research to elucidate clinical implications of gadolinium deposition. The Pharmacovigilance 

Risk Assessment Committee of the European Medicines Agency

 has proposed a ban on all linear agents. Radiologists from the 

 have recommended that use of macrocyclic rather than linear agents be considered, if possible.

Implications for MRI utilization in gynecology


	MRI imaging of the pelvis is indicated to further characterize masses seen on computed tomography (CT) or ultrasound. An MRI without contrast offers sensitivity comparable to CT with contrast and superior specificity in diagnosis of adnexal malignancy following an indeterminate ultrasound.

 MRI provides better assessment of soft tissue structures and improved localization of pelvic masses, which is useful to discriminate between ovarian and uterine pathology. T2-weighted imaging is helpful in determining whether the lesion is a unilocular cyst, mixed solid and cystic, or homogeneously solid. T1-weighted imaging without and with fat saturation allows for detection of adnexal lesions containing macroscopic fat. Fat-saturated T1-weighted imaging is useful for identifying ovarian endometriomas, extraovarian endometriosis, and other lesions with blood degradation products, such as hemorrhagic cysts.

 Adding contrast may allow better discrimination between benign and malignant pathology due to the kinetics of contrast enhancement and washout, although its use may vary by institutional MRI protocol. 

The incremental additional clinical information that is gained with use of GBCA in MRI evaluation of variant pelvic anatomy and suspected benign pathology is small. Adding GBCA has been shown to improve evaluation of myometrial invasion from endometrial carcinoma

 and identification of the correct primary tumor when there are multiple sites of biopsy-proven uterine adenocarcinoma.

 Contrast may also be useful in identifying vulvar cancers and occult inguinal metastases

 and it has shown to be useful in identifying neoplastic nodules within complex adnexal lesions and distinguishing endometriosis from pelvic inflammatory disease.

Breast cancer screening in high-risk women


	Intensive breast cancer surveillance is advised for women at the highest risk of breast cancer. Women with inherited genetic susceptibility due to 

 and other less well-known germline mutations (CHEK2, ATM, PALB2), family history, prior chest radiation (cumulative dose > 10 Gy before age 30), or calculated lifetime risk of breast cancer exceeding 20% or more are advised to start breast cancer screening between ages 25 and 30.

 While mammography remains the gold standard for breast cancer screening in the general population, it has been less successful in detection of early, curable cancers in higher-than-average-risk patients. Prospective studies of annual mammography in 

-positive women showed an interval cancer rate of 35% to 50% and the majority of invasive cancers were > 1 cm and 20% to 56% of them had lymph node involvement.

 Some factors cited to explain the poorer detection of 

-associated breast cancer may relate to the confounding effect of breast density, which is more common in younger women. Mammography relies upon abnormal tissue density, tissue distortion, and calcifications to identify breast cancers. 

-associated breast cancers tend to be less mammographically detectable than sporadic breast cancers, which has been attributed to their distinctive histologic growth patterns, such as pushing borders, the relative absence of associated ductal carcinoma in situ, and high cellularity.

In observational studies, adding contrast-enhanced MRI to annual mammography in BRCA mutation carriers significantly improved detection of early, treatable breast cancers with a combined sensitivity of 94% compared to 39% with mammography alone.

 MRI provides a functional assessment of breast tissue. Contrast- enhanced MRI can detect microvascular changes and peritumoral inflammation as the contrast accumulates rapidly, and is then washed out rapidly, in more vascular tumors compared to benign breast tissue. Consequently, annual contrast-based MRI has been incorporated into breast cancer surveillance guidelines for women at the highest risk of breast cancer.

There has been no change to the recommendation of annual breast MRI by the 

 due to the increased benefit of early detection of cancer in these high-risk patients.

 In view of the concerns raised over GBCA, macrocyclic agents are advised, and alternatives to conventional MRI imaging are being investigated. These include investigations of lower-dose gadolinium scans

 or alternative MRI contrast agents such as Feraheme (ferumoxytol an ultrasmall, superparamagnetic iron oxide nanoparticle), which is currently used for vascular imaging.

Some high-volume centers enriched with populations of BRCA mutation carriers have amended the recommended surveillance for women at high risk of breast cancer. Breast ultrasound may be alternated with annual MRI, in addition to annual mammography. Ongoing study of novel strategies to improve the mammogram, such as use of iodinated contrast and breast tomosynthesis, which creates a 3-D image of the breast by stacking multiple 2D mammographic renderings, are underway in women with BRCA mutations. Such advances may allow reduction in cumulative exposure to GBCA in these high-risk women.

Weighing risks and benefits in women at high risk


	While it’s discomforting to consider progressive accumulation of gadolinium in the body over time, the clinical consequences and level of risk associated with GBCA are, as yet, unknown. On the contrary, the consequences of missing an aggressive breast cancer are all too well known. In the absence of an effective non-gadolinium alternative to GBCA, until we have more definitive data on the true risk of gadolinium deposition, we forego surveillance of women at high risk of breast cancer with contrast-enhanced MRI at our peril. Best practice suggests that providers consider the necessity of contrast based upon clinical circumstances, and that macrocyclic rather than linear agents be used when necessary.

 Judicious use of gadolinium, coupled with vigilance in identifying women who might be pregnant, can minimize inadvertent fetal exposure to gadolinium, which is estimated to occur in 1 in 860 pregnancies in the United States.

The authors report no potential conflicts of interest with regard to this article.

Kanda T, Osawa High signal intensity in dentate nucleus on unenhanced T1 weighted MRI images: association with linear versus macrocyclic gadolinium chelate administration. 

Roberts DR, Holden KR. Progressive in of T1 signal intensity in the dentate and nucleus and globus pallidus on unenhanced T1-weighted MR images in the pediatric brain exposed to multiple doses of gadolinium contrast. 

Robert P, Lehericy S, Grand S, et al. T1 weighted images hypersignal in the deep cerebellar nuclei after repeated administrations of gadolinium-based contrast agents in healthy rats: difference between linear and macrocyclic agents. 

Terashima KH, Reich DS. Gadolinium deposition: practical guidelines in the face of uncertainty. 

FDA Safety Communication 5/16/2018 Update https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-gadolinium-based-contrast-agents-gbcas-are-retained-body

Gulani V, Calamante FG, Shellock FG, et al. Gadolinium deposition in the brain: summary of evidence and recommendations 

American College of Radiology. Committee on Drugs and Contrast Media. ACR Manual on Contrast Media, Version 10.3. Available at https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Contrast_Media.pdf Accessed April 10, 2018.

European Medicines Agency. PRAC concludes assessment of gadolinium agents used in body scans and recommends regulatory actions, including suspension of for some marketing authorizations. March 2017 Available at 

http://www.ema.europa.eu/docs/en_GB/documnent_library/Press_release/2017/03

Kinkel K, Lu Y, Mehdizade A, et al. Indeterminate ovarian mass at US: incremental value of second imaging test for characterization–meta-analysis and Bayesian analysis. 

Masch WR, Daye D and Lee SI. MRI imaging for incidental adnexal mass characterization. 

Ha HK, Lim YT, Kim HS, et al. Diagnosis of pelvic endometriosis: fat-suppressed T1-weighted vs conventional MR images. AJR 

Bazot M, Bharwani N, Huchon C, Kinkel K, et al. European society of urogenital radiology (ESUR) guidelines: MR imaging of pelvic endometriosis. 

Nougaret S, Horta M, Sala E, Lakhman Y, et al. Endometrial Cancer MRI staging: Updated Guidelines of the European Society of Urogenital Radiology. 

Vargas HA, Akin O, Zheng J, Moskowitz C, et al. The value of MR imaging when the site of uterine cancer origin is uncertain. 

Kataoka MY, Sala E, Baldwin P, et al. The accuracy of magnetic resonance imaging in staging of vulvar cancer: a retrospective multi-centre study. 

Suzuki S, Yasumoto M, Matsumoto R, Andoh A. MR findings of ruptured endometrial cyst: comparison with tubo-ovarian abscess. 

Tanaka YO, Okada S, Yagi T, et al. MRI of endometriotic cysts in association with ovarian carcinoma. 

Warner E, Plewes DB, Hill KA, et al. Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. 

Monticciolo DL, Newell MS, Moy L, Niell B, Monsees B, Sickles EA. Breast cancer screening in women at higher-than-average risk: recommendations from the ACR. 

Brekelmans CTM, Saynaeve C, Bartels CC, et al. Effectiveness of breast cancer surveillance in BRCA1/2 gene mutation carriers and women with high familial risk. 

Warner E. Screening BRCA1 and BRCA2 mutation carriers for breast cancer. 

Lee JM, McMahon PM, Kong CY, et al. Cost-effectiveness of breast MR imaging and screen-film mammography for screening BRCA1 gene mutation carriers. 

Warner E Messersmith H, Causer P, et al. Systematic review: Using MRI to screen women at high risk of breast cancer. 

Daly MB. PIlarski R, Berry MP, Buys SS et al. Genetic/familial high risk assessment: breast and ovarian cancers. Version 2.2019. Available at 

https:///www.nccn.org/professionals/physician

Rowley H. To be alarmed or not to be alarmed over gadolinium contrast revelations: That is the question. European Congress in Radiology 2017 Annual Meeting. Available at 

BIRI Registry for Development and Validation of Novel MR Imaging Techniques, Cedars-Sinai Medical Center PI Dr Debaio Li (correspondence)

Shahrouki P, Moriarty JM, Khan SN, et al. High resolution, 3-dimensional Ferumoxytol-enhanced cardiovascular magnetic resonance venography in central venous occlusion. 

Bird S, Gelperin K, Sahin L et al. First-trimester exposure to gadolinium-based contrast agents: a utilization study of 4.6 million U.S. pregnancies. 

Concerns have been raised about the safety of GBCA. Experts review the latest data to support counseling of patients who may have repeated exposure.

Ilana Cass, MD

Articles

Keeping Politicians Out of the Exam Room

The value of GBCA in MRI images

8 examples of how GBCA improves MRI

Gadolinium-based contrast in breast MRI: What ob/gyns need to know