Burden of anemia in women with uterine fibroid-associated heavy menstrual bleeding.

Laura McKain: Writing – review & editing, Writing – original draft, Conceptualization. Brenna L. Brady: Writing – review & editing, Formal analysis, Data curation, Conceptualization. Anh Thu Tran: Writing – review & editing, Formal analysis, Data curation, Conceptualization. Cassandra Lickert: Writing – review & editing, Project administration, Conceptualization.

This analysis demonstrates that anemia is particularly common in women who have UF who are symptomatic with HMB. Following the diagnosis of UF accompanied by anemia, women exhibited a higher propensity for undergoing treatments, notably invasive procedures, with hysterectomy being a predominant choice. Women with a UF diagnosis, with or without HMB or anemia, had significantly higher all-cause and obstetrics/gynecology-related costs than women without a UF diagnosis, with the combined presence of HMB and anemia amplifying the clinical and economic burden compared with UF alone.

Women with UF experience distressing symptoms, including pain, HMB, and bulk symptoms, 2 , 3 , 16 , 27 that can negatively impact quality of life 2 , 17 and may require treatment. Women with UF and HMB also experience high rates of anemia, 6 which can further contribute to symptom burden. 15 Our analysis adds to existing evidence of high symptom burden associated with UF and the additional burden that comes with HMB and anemia. Few studies have evaluated the prevalence of anemia in women with UF and HMB. 6 , 27 , 28 In agreement with a prior retrospective analysis that demonstrated greater symptom burden, including anemia, in women with UF and HMB compared with women with UF only, 27 our study also found higher rates of anemia in women with UF and HMB vs UF alone. This contrasts with another retrospective analysis in which anemia prevalence was as high as 75% in women with various types of UF but did not correlate with HMB. 28 Notably, our analysis revealed that anemia was frequently identified before the diagnosis of UF or HMB, suggesting that routine detection of anemia through laboratory tests may prompt further clinical evaluation. Alternatively, UF and HMB may be undetected until symptoms are severe, suggesting that screening for HMB could be beneficial for earlier anemia and UF diagnosis. Treatment and management of anemia includes iron supplementation (oral or intravenous) and, in more extreme cases, blood transfusions. 25 , 26 Unsurprisingly, and in line with a prior study, 6 our analysis shows higher rates of blood transfusions in women with anemia compared with those without anemia. Although a study by Morrison et al 6 did not observe higher rates of hysterectomy in women with HMB and anemia, this analysis and the analysis by McKain et al 27 demonstrated higher rates of hysterectomy in women with UF with HMB compared with UF alone. 27 Higher rates of blood transfusions and hysterectomy may partially explain the increased rates of ER visits and inpatient admissions in the UF cohorts of women with anemia compared with those without, as suggested by our analysis. A comparative cost analysis estimated that the economic burden of UF in the US increased from $34.4 billion in 2010 to $42.2 billion in 2022, driven in part by increased costs of surgical management. 29 In the current study, UF with HMB was associated with both increased all-cause and obstetrics/gynecology-related healthcare costs. Higher rates of anemia, hysterectomies, and blood transfusions in the cohorts of women with HMB suggest that these outcomes may account for the increased cost of care for these cohorts. Indeed, women with anemia in all cohorts had higher all-cause and obstetrics/gynecology-related healthcare costs compared with women without anemia. These results are consistent with results from Morrison et al, 6 which showed that the cost of hospitalization was over 13% higher for women with anemia compared with those without anemia, primarily due to additional services required during hospitalization. Our analysis revealed a pattern in the timing of anemia recognition, with most diagnoses in the UF-HMB cohort and nearly half in the HMB-UF cohort occurring only after the diagnosis of UF. This suggests that anemia may often go unnoticed by clinicians until symptoms become severe. Potential contributing factors include clinicians not routinely screening menstruating women for anemia, failing to inquire about the heaviness of menstrual cycles, or societal normalization of symptoms causing women to underreport or dismiss them. These findings highlight the need for increased vigilance in evaluating both anemia and menstrual symptoms to enable earlier diagnosis and intervention. Our study provides a descriptive analysis of the effects of anemia on HCRU and costs for UF cohorts; however, additional analyses are warranted to further inform these results. Further research is needed to understand how various treatments for UF-associated HMB affect clinical and economic burden. In the phase 3 UF-1 and UF-2 trials, twice-daily elagolix combination therapy (elagolix 300 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) reduced HMB in women with UF-associated HMB and improved anemia. 24 In the international, phase 3 LIBERTY clinical trials and extension studies, once-daily relugolix combination therapy (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) in women with UF and HMB also decreased HMB and improved anemia and health-related quality of life compared with placebo. 23 , 30 , 31 , 32 In our analysis, prescriptions for GnRH agonists and antagonists were relatively low compared with other treatment options, potentially owing to the relatively recent FDA approvals. Future studies should investigate whether these therapies reduce reliance on surgical interventions, lower HCRU, and improve cost-effectiveness in real-world settings. Moreover, understanding patient and clinician factors influencing the adoption of these therapies—including adherence, tolerability, and equity in access—could further inform strategies to optimize care for women with UF and HMB. Strengths include the large sample size and cohort matching, which minimized demographic differences between cohorts at baseline. Limitations include those inherent to retrospective claims analysis as they are descriptive in nature, which limits conclusions regarding causality. Owing to slight imbalances between UF and control cohorts in non-Black races, region of residence, and health plan type that remained after matching, our analysis was unable to evaluate differences related to race, region, and health plan type. The study was limited to women with commercial health coverage; therefore, results may not be generalizable to those with other insurance types or without healthcare coverage. Owing to the nature of retrospective studies and claims data, access to specific information may be limited. Methods of diagnosis were not assessed, and how diagnoses were derived from images was unavailable in the claims database. Additionally, the absence of detailed clinical characteristics, such as lesion size, numbers, or FIGO classification may limit the interpretation of findings, as certain UF characteristics may not be clinically associated with HMB. Claims data may be subject to coding errors leading to potential misclassification owing to billing processes and administrative claims being the primary source of collection as opposed to medical records. Recognition of HMB and/or anemia may also be influenced by diagnosis bias after imaging findings or during preoperative evaluation. Although a 12-month period without a UF claim was imposed before index to increase the certainty that the index date represented the first UF diagnosis, without full medical histories, we cannot exclude the possibility that women had prior UF claims >1 year before index.

This study used Merative MarketScan Commercial Database claims data from October 1, 2015, to June 30, 2022. The study included women who were 18–55 years old with newly diagnosed UF, defined as ≥1 inpatient claim for UF or ≥2 nondiagnostic outpatient claims for UF occurring ≥30 days apart. The first qualifying UF claim served as the index date. Preindex was defined as the 12 months before the first qualifying UF claim (index), during which baseline characteristics and medical history were assessed. Postindex was defined as the 12 months after the first qualifying UF claim (index). Treatments, HCRU, and costs were assessed in preindex and postindex periods. Individuals with claims for UF during the preindex period were excluded as they represented prevalent UF cases. Eligible women with UF were categorized into cohorts based on the presence and order of HMB claims: UF only, UF then HMB (UF-HMB), and HMB then UF (HMB-UF). To control for age-related confounding, eligible women in each UF cohort were matched 1:1:1 by age, resulting in final UF cohorts of equal size. A control (non-UF/non-HMB) cohort was identified, which included women with no claims for UF or HMB during the study period and was matched 5:1 to the 3 UF cohorts by age. The index date for the control cohort was a random obstetrics/gynecology visit occurring during the same period as the UF cohort date ( Figure 1 ). All women were required to have continuous medical and pharmacy eligibility and no claims for malignancy other than non-melanoma skin cancer during preindex and postindex periods. Women in UF and control cohorts were further classified into 4 categories based on presence of anemia: (1) anemia occurring preindex, (2) anemia occurring postindex, (3) anemia occurring postindex only (ie, newly diagnosed; a subset of those with postindex anemia), and (4) no anemia postindex. Figure 1 Study design. The study period was defined as October 1, 2015, to June 30, 2022. Women were selected and categorized into cohorts based on the presence and order of HMB claims or as control during the patient section window (October 1, 2016, to June 30, 2021). The index date was defined as the date of the first UF claim for the UF cohorts and a random OB/GYN visit date for the control cohort. HMB, heavy menstrual bleeding; OB/GYN, obstetrics and gynecology; UF, uterine fibroids. Figure 1 dummy alt text McKain. Burden of anemia in women with uterine fibroid-associated heavy menstrual bleeding. AJOG Glob Rep 2026. Study design. The study period was defined as October 1, 2015, to June 30, 2022. Women were selected and categorized into cohorts based on the presence and order of HMB claims or as control during the patient section window (October 1, 2016, to June 30, 2021). The index date was defined as the date of the first UF claim for the UF cohorts and a random OB/GYN visit date for the control cohort. HMB, heavy menstrual bleeding; OB/GYN, obstetrics and gynecology; UF, uterine fibroids. Demographics and clinical characteristics were assessed at index. Study outcomes were reported preindex and postindex. Outcomes assessed included UF-related comorbid conditions, UF-related symptoms, treatment characteristics, and UF-related procedures. All-cause and gynecology-related HCRU (inpatient visits, emergency room [ER] visits, outpatient office visits, other outpatient services, and outpatient pharmacy claims) and costs were assessed. Cost outcomes were based on the paid amounts of adjudicated claims. Gynecology-related HCRU and costs were identified based on presence of a gynecology-related diagnosis code on the claim line. All outcomes were defined via International Classification of Diseases, 10th Revision, Clinical Modification codes; Current Procedural Terminology 4th edition codes; Healthcare Common Procedure Coding System codes; or National Drug Codes appearing in the administrative claims record ( Supplemental Tables 1-3 ). This study used deidentified patient records and therefore did not require Institutional Review Board approval. Chi-square or Fisher’s exact test (categorical variables) and t-test (continuous variables) were used to compare differences in outcomes between the 3 UF cohorts and the control cohort.

These findings emphasize the importance of recognizing signs and symptoms that may lead to the diagnosis of UF. Early recognition and detection of UF may allow for earlier treatment that can alleviate related conditions such as HMB and anemia before they become severe. This study highlights potential gaps in both patient and provider awareness, emphasizing the value of inquiries about menstrual health and the necessity of appropriate screening for anemia. Ongoing efforts in patient and provider education and discussions around shared decision-making are essential to improving outcomes and addressing the clinical and economic burdens of UF-related conditions.

Uterine fibroids (UF), common, benign uterine tumors, were estimated to affect over 226 million women globally in 2019. 1 Heavy menstrual bleeding (HMB) is one of the most commonly reported symptoms of women with UF 2 , 3 and is often associated with iron-deficiency anemia. 4 , 5 A retrospective database analysis revealed that >25% of women with HMB had a diagnosis of anemia, 6 with HMB the potential underlying cause for up to 30% of all iron-deficiency anemia cases. 7 Absolute iron deficiency most often affects women 18 to 50 years of age, 8 coinciding with ages in which UF are most prevalent. 1 Anemia has been associated with increased risk of serious clinical events such as myocardial infarction and acute ischemic stroke, 9 , 10 and increased healthcare resource utilization (HCRU), including inpatient hospitalizations and transfusions. 6 , 11 These findings underscore the critical importance of recognizing and addressing anemia as a UF-related symptom. Additional UF symptoms include pain, bulk symptoms such as pelvic pressure and increased urination frequency or volume, and infertility. 3 , 12 , 13 , 14 Iron-deficiency anemia can exacerbate symptom burden, leading to fatigue, lack of energy, and weakness. 15 Women with UF also report psychological distress, feelings of helplessness, negative body image and sexuality, and lack of support. 16 Despite high prevalence and significant symptom burden in women with UF, results of a survey of US women suggest that at-risk women may not seek appropriate medical treatment. 17 Delay in care may result from lack of knowledge, 18 stigma, 16 normalization of symptoms, or lack of access to healthcare. 17 , 18 Additionally, there can be a significant gap between the onset of symptoms and a formal diagnosis, even among women who do seek care. In a cross-sectional survey of US women, respondents averaged ∼3.6 years before seeking treatment for UF, with 32% waiting more than 5 years. 19 Evidence from a separate survey of US women also suggests that women who experience the most severe symptoms and lowest quality of life are those without a clinical diagnosis. 17 Treatment options for UF include expectant management, pharmacotherapy, and interventional and surgical procedures. 20 The American College of Obstetricians and Gynecologists recommend an individualized treatment approach that involves shared decision-making, balancing patient symptom burden and treatment goals with risks of treatment options. 20 Pharmacologic options include hormonal contraceptives, tranexamic acid, gonadotropin-releasing hormone (GnRH) agonists, 20 and newer therapies such as GnRH antagonists in combination with estradiol and norethindrone acetate, which have been approved by the US Food & Drug Administration (FDA) for the treatment of UF-associated HMB. 21 , 22 In particular, recent clinical studies evaluating GnRH antagonists in combination with estradiol and norethindrone acetate demonstrated reduction in HMB 23 , 24 and anemia 23 in women with UF. For women with anemia, the American Society of Hematology recommends identifying and treating the underlying cause of iron-deficiency anemia. 25 Depending on the identified underlying cause, treatment might involve addressing dietary history, managing medical conditions with medication, or interventions to stop bleeding sources, 25 , 26 which may contribute to increased HCRU and costs. 6 The additional incremental burden of HMB and anemia in women with UF and associated costs of care remain unclear. Limited data are available on the prevalence of anemia in women with UF, with or without HMB. The objective of this retrospective observational study was to describe the clinical burden of anemia and HMB in women diagnosed with UF and overall cost of care associated with the additional incremental burden of both anemia and HMB in UF.

The data that support the findings of this study are available from Merative via a license, which includes terms and conditions around its appropriate use and licensing fees.