Fibroids and health disparities: the COllaboration for EQuity in Uterine Leiomyomas specialized center.

Uterine fibroids and their associated health disparities for Black individuals are a key problem for not only affected individuals and their families, but their employers and society at large. Enlarging the examination of barriers is key in not only improving these barriers but improving health outcomes for all affected individuals. The COEQUaL Specialized Center will attempt to utilize the NIMHD research framework to elucidate the barriers to fibroid care at multiple levels with a goal of eliminating health disparities for Black individuals with uterine fibroids.

Uterine fibroids (leiomyomas or myomas) are common non-cancerous myometrial neoplasms that affect up to 75% of all individuals with a uterus. Fibroid symptoms are not benign and include heavy or prolonged menstrual bleeding and resultant anemia, both menstrual and non-menstrual pain and pressure, bowel, bladder and reproductive dysfunction. 1 – 3 Fibroids are also the leading cause of hysterectomy. 4 Fibroids are more prevalent and severe in Black/African American (Black) individuals making fibroids a disease of significant health disparities. 4 – 10 Black individuals with fibroids have an earlier age at onset, 6 , 11 more severe disease, 1 , 2 , 6 , 12 up to a 7-fold increased risk of surgical myomectomy, 9 more difficulty finding good information about the disease, 7 , 8 and additional barriers to accessing values-congruent care. 10 , 13 In a study published a decade ago, fibroids cost the US healthcare system $34.4 billion annually in direct treatment costs. 14 There are also indirect costs including lost wages due to debilitating symptoms, the cost of sanitary protection, the cost of lost work productivity, reproductive impairment resulting in infertility, pregnancy loss, and pregnancy complications. Additionally, while nearly 3 in 4 individuals report desiring uterine preserving options, 7 , 8 , 13 nearly 3 in 4 individuals undergoing surgical therapy undergo hysterectomy. 15 , 16 A recent study suggested that among individuals with commercial insurance undergoing hysterectomy for fibroids, nearly 3 of 5 did not have any conservative therapy prior to the hysterectomy. 17 This overuse of hysterectomy is a problem not only because individuals desire alternatives to hysterectomy. Our work and that of others has demonstrated increased cardiovascular and mental health morbidity following hysterectomy even with bilateral ovarian conservation when compared to individuals with no surgery after adjustment for differing risk factors. 18 – 22 Some studies also demonstrate increased mortality when hysterectomy is performed in individuals younger than age 35. The magnitude of these risks are substantial. One study with a mean follow-up of almost 22 years, found an adjusted 4.6-fold increased risk of congestive heart failure and a 2.5-fold increased risk of coronary artery disease for individuals undergoing hysterectomy with ovarian conservation at age 35 or younger. 18 This length of follow-up would place these individuals shortly after menopause when cardiac disease just starts to rise. Thus, understanding barriers to wider use of appropriate alternatives to hysterectomy for symptomatic fibroids is critical. In the past two decades there has been development of many alternatives to hysterectomy including effective medical ( e.g. levonorgestrel-releasing IUDs, oral gonadotropin releasing hormone agonist combinations), procedural (e.g. uterine artery embolization and focused ultrasound ablation), and surgical (e.g. hysteroscopic and laparoscopic radiofrequency ablation and hysteroscopic and robotic myomectomy) options 4 . There also appears to be undertreatment of Black individuals with fibroids with uterine sparing options early in their fibroid journey. 23 The CO llaboration for EQ uity in U terine L eiomyomas (COEQUaL), establishes a Specialized Center that combines the strengths and synergies of researchers at the Fibroid Foundation, Mayo Clinic, University of Florida College of Medicine-Jacksonville, University of Mississippi Medical Center, and others to address these issues. The COEQUaL Specialized Center has two overarching goals to 1) improve outcomes for all individuals with fibroids and 2) eliminate fibroid health disparities for Black individuals. To accomplish these goals, COEQUaL aims to identify affected individuals earlier, understand and meet their needs, remove internal and external barriers to care, quantify the association between Medicaid expansion and access to fibroids care, optimize communication between individuals and providers, and utilize modern technology to achieve optimized fibroid care ( Figure 1 ). COEQUaL will utilize a patient-centric behavioral and/or social science research approach utilizing the National Institute on Minority Health and Health Disparities (NIMHD) Research Framework.( Figure 2 ) 24 When attempting to explain why uterine-sparing alternatives to hysterectomy have not been more widely used, a myriad of questions arise. Are affected individuals unable to access knowledgeable and proficient healthcare providers? Are individuals with fibroids hearing about alternatives to hysterectomy but have unaddressed safety concerns? Are providers not offering these therapies because they are not familiar with literature or are biased toward surgery? Is insurance not covering alternatives or making preauthorization so onerous that providers avoid prescribing? We are seeking to answer these questions. Individuals with fibroids have multifaceted symptoms that are often dismissed or diminished. They experience heavy or prolonged menstrual bleeding routinely lasting 7 days or more per month which often results in significant anemia. Yet our research, and that of others, shows that individuals are often falsely reassured by family or health care providers they are having normal menstruation. 25 , 26 Individuals with fibroids have pain, pressure, and extrinsic compression of bowel, bladder and other structures, despite widespread belief that pain is not a symptom of fibroids. Our recent research demonstrates that medical treatment with oral gonadotropin releasing hormone antagonists, medications approved for fibroid-related bleeding, decreases fibroid-related pain to nearly no pain with menses and throughout the non-menstrual interval. 27 This dismissal and diminishment of the patient experience is less well characterized in terms of reproductive dysfunction (i.e . infertility, recurrent pregnancy loss and pregnancy complications) but likely no less pernicious. 28 – 30 Not only is the physical disease burden ( e.g . uterine size, number of fibroids, earlier age at onset) increased in Black individuals but so is the socioenvironmental impact. As early as 2007, studies reported that chronic stress and experiences of racism were linked to fibroids. 31 , 32 We termed this disparity a Public Health issue in 2014 10 and have continued to document these barriers in access to information and to care. Much has been written about the historic distrust of the medical system by Black individuals with the U.S. Public Health Service Untreated Syphilis Study at Tuskegee cited as the leading example. 33 However, there is an arguably more substantial legacy of unethical care and lack of reproductive justice that underpins and reverberates through the gynecologic care for fibroids for Black individuals. Gynecologic surgery itself was innovated by surgical procedures on enslaved individuals without anesthesia. 34 , 35 There is a complicated legacy where individuals believed they were having surgery for one reason, often fibroids, and instead had a sterilization or hysterectomy to which they had not consented, leading to the term “Mississippi appendectomy” to indicate these coerced surgeries. 36 – 38 There has also been contemporary reports of instances where fibroids or other gynecologic disease in Black individuals were associated with adverse outcomes and unequal treatment with reverberations for the woman 39 or surviving family members. 40 Thus, understanding the problems of fibroid care from patient, community, health care provider, and societal viewpoints is critical. Not only does the fibroid disease present across a broad spectrum of varying size, number, and symptoms, but the context of fibroid decision-making regarding treatment also differs widely. Even with equivalent fibroid burden, a 26-year-old who prioritizes symptom relief while she finishes medical school will have different treatment needs and desires than the 26-year-old woman who has infertility and is preparing to undergo in vitro fertilization. Likewise, the needs of a 40-year-old woman may differ based on occupation, desire for childbearing and family history of age at menopause. Prioritizing precision health and shared decision making is key goal for fibroid care. 13 The introduction of oral GnRH antagonist combinations (OGAC) to fibroid clinical care illustrates that barriers to care are present but also the possibility of dissemination of effective therapy to more individuals. OGACs treat both heavy menstrual bleeding and bulk symptoms and have been available since the 2020 FDA approval of elagolix combination therapy 41 and the subsequent 2021 approval of relugolix combination therapy. 42 – 44 Importantly, both medications demonstrate that there is no limitation of efficacy based on extent of fibroid disease, 45 , 46 or the presence of concomitant adenomyosis, 47 and provide further evidence of their effectiveness in treating menstrual and non-menstrual pain 27 and improving quality of life. 48 Both combinations have low levels of side effects and contain levels of estradiol and progestin equivalent to the early follicular phase. These two combination formulations are currently approved in the US for 24 months of use but approved for unlimited duration of therapy in the European Union. 46 , 49 The American College of Obstetricians and Gynecologists (ACOG) practice bulletin rates the evidence for OGACs for fibroid treatment as higher than that for oral contraceptive treatment for uterine fibroids, which they rate as based on expert opinion. 50 Despite the limited evidence for their efficacy, our prior work demonstrated that oral contraceptives made up over 75% of medical therapies in a commercially-insured population. 50 , 51 Despite robust evidence of efficacy and safety for OGAC across the spectrum of fibroid disease, use has been limited raising the question whether there are barriers to information dissemination or unacknowledged safety concerns. Both medications carry a Black box warning about thromboembolic disease because they contain estrogen and progestins. 41 , 42 However, in contrast with combination estrogen-progestin contraceptives, which employ pharmacologic doses of estrogen and progestins and clearly elevate risk of thromboembolism, risk with OGACs is markedly lower because they contain low doses of hormones, resulting in levels similar to the early follicular phase. 44 Recent advocacy has focused on this one-size-fits-all steroidal Black box warning that some believe limits the appropriate use of low dose vaginal estrogen for treatment of genitourinary syndrome of menopause. 52 Thus, understanding the perceived benefits, risks and alternatives to OGACs for individuals, the knowledge barriers and biases of providers, and the role of insurance coverage, copays and preauthorizations may allow for more effective medical treatment of individuals earlier in their disease process if they are able to be utilized before a referral to a gynecologist. Similarly, gynecologists often see individuals electing surgical excision over procedural treatment options such as uterine artery embolization. Often the stated reason is they desire the removal of the fibroids. Does that surgical bias represent a lingering concern that a “fibroid tumor” is a malignant tumor? How is the best way to discuss the high rate of new fibroid formation following conservative surgery? These and other issues can be elucidated by COEQUaL projects. A key premise of COEQUaL is that treating individuals earlier in their disease process will likely result in better outcomes for all individuals, increased health equity for Black individuals and lower rates of hysterectomy as Black individuals develop fibroids at an earlier age. It will also help patients and clinicians to identify appropriate alternatives to hysterectomy. The three COEQUaL projects were developed to advance individualized therapy for all individuals with fibroids. COEQUaL includes experts from gynecology, bioethics, community engagement, epidemiology, healthcare economics, statistics and other fields to address specific aims of the Center. Each project, designed to directly address COEQUaL’s goals, includes a multi-disciplinary team. The sites were chosen not only for their expertise but to provide a diversity of patient and healthcare provider experience. In Project 1, we will engage with communities in our three geographic regions of the upper Midwest, Northern Florida, and central Mississippi to understand individual needs and preferences regarding: information about normal menstruation and how fibroid-related symptoms can disrupt it; awareness of fibroids and early signs of their presence; and barriers to early diagnosis, the full spectrum of treatment options, and effective care and recovery. We chose diverse geographic regions to understand regional differences as well as differences between urban and rural environments. By engaging with individuals both before and after dissemination we will be able to assess whether 1) there is an increase in awareness of fibroids and normal menstruation among participant’s communities, 2) if the dissemination efforts changed the perception of some identified structural barriers (i.e. cultural and social norms) and 3) if the dissemination improved shared decision making in treatment choice. However, structural barriers, such as length of travel to values-congruent care (geography), insurance access, or lack of knowledgeableproviders may continue to delay or prevent the full range of care. Engagement will include focus groups with individuals who have experienced fibroids and subsequently received both surgical and non-surgical care. We will also evaluate knowledge of abnormal menstrual bleeding, pain and bulk-related symptoms and fibroids among adolescent and young adult individuals and use a peer coaching model to increase awareness of fibroid signs, symptoms and treatment options. In the second half of the project, we will develop a targeted public awareness campaign with our advisory board designed to increase knowledge of early signs and symptoms of fibroids, advice on navigating the diagnostic pathway, and the full range of available treatment options. After dissemination, we will re-engage community members to assess the success of the campaign and offer advice on how it can be iteratively improved to offer continuous education on uterine health. In Project 2, we will examine healthcare system factors that influence the treatment of uterine fibroids among Black individuals receiving care from providers in multi-specialty healthcare systems. There are three aims for this project. First, we will examine factors which differ between Black and White individuals receiving fibroid treatment in a commercially insured population. Second, we will assess the impact of Medicaid expansion on access to fibroid treatments by comparing fibroid-related care utilization and outcomes between pairs of contiguous U.S. states where only one state expanded Medicaid. Third, we will explore providers’ use of evidence-based treatment options and healthcare system barriers to optimized use when providing fibroid care. For this aim we will concentrate on providers in specialties beyond obstetrics and gynecology including those in internal medicine, family medicine, and pediatrics since individuals are more likely to encounter these practitioners earlier in their symptomatic journey with fibroids. We will also assess the care provided by both physicians and advanced practice providers (e.g. nurse practitioners and physician assistants) in these mixed methods studies. Finally, in Project 3 we will look for societal barriers and technological solutions such as electronic health record risk prediction models, and polygenic risk scores to predict incident fibroids to aid in screening as well as predictors of progression to hysterectomy following conservative therapy. In project 3, we will confer with healthcare, research, and patient advisory boards to determine the acceptability of new technologies and utilization of the electronic health record and polygenic risk scores to identify individuals at risk for fibroids, assessing ways to acknowledge and anticipate the historical issues and ongoing considerations in this field such as how personal health information might contribute to insurance or employment discrimination . Additionally, the two COEQUaL cores, Administrative and CPEO add to the mission. In addition to providing administrative support to all facets of the projects, the COEQUaL administrative core will fund an annual pilot project for an Early-Stage Investigator to grow the field of fibroid investigators. They will also host regular meetings of the multidisciplinary Internal and External Advisory Committees to get feedback on all research activities. The CPEO core will not only disseminate the results of the COEQUaL research but aims to disseminate all information about fibroids from a research and societal perspective through programs such as the Fibroid Friday program ( coequalstudy.org ). The CPEO core will also interact with each project when community engagement is required or requested.