A new analysis published in Blood Advances indicates that a single dose of intravenous (IV) iron dextran may be the most cost-effective initial treatment for iron deficiency anemia (IDA) in reproductive-age women experiencing heavy menstrual bleeding.
IDA affects nearly a third of women globally, with a higher prevalence among those with heavy menstrual bleeding, defined as monthly blood loss exceeding 80 mL or causing significant daily disruption. Oral iron supplementation is typically the first-line therapy in the United States due to its lower upfront cost and ease of administration. However, oral formulations are frequently associated with gastrointestinal side effects and incomplete absorption, which can reduce patient adherence and delay effective iron repletion.
Daniel Wang, a study author from Yale School of Medicine, stated that while oral iron appears less expensive and more convenient initially, the study found IV iron to be the preferred first-line treatment, offering the highest value for cost and substantially improving quality of life.
Cost-Effectiveness Modeling
Investigators utilized a Markov simulation model to compare iron replacement strategies over the reproductive lifespan of women with IDA and heavy menstrual bleeding (ages 18 to 51). The analysis evaluated first-line treatment with IV iron dextran, IV iron sucrose, IV ferumoxytol, and alternate-day oral ferrous sulfate. Outcomes were assessed over three-month cycles from a societal perspective, factoring in both direct medical costs and indirect costs, such as lost wages during infusion visits.
The base-case model assumed an average menstrual blood loss of 120 mL per month and a net iron deficit of 35 mg monthly. Under these conditions, IV iron dextran was projected to resolve IDA for approximately 30 months after a single 1000-mg infusion. In contrast, patients receiving oral ferrous sulfate were projected to return to a clinically significant iron deficit approximately every 36 months, reflecting slower iron repletion and ongoing losses.
Value was assessed using incremental cost-effectiveness ratios (ICERs) and net monetary benefit (NMB), with quality-adjusted life years (QALYs) as the primary effectiveness outcome.
Economic Outcomes
In the base-case analysis, IV iron dextran resulted in 19.26 QALYs at a lifetime cost of $157,500. Oral ferrous sulfate yielded 19.10 QALYs at a cost of $152,900. This translated to an ICER of $28,600 per QALY gained for IV iron dextran, a value below commonly accepted U.S. willingness-to-pay thresholds. IV iron dextran also showed a higher incremental net monetary benefit compared to oral iron.
The cost-effectiveness of IV iron dextran was maintained in sensitivity analyses simulating heavier menstrual bleeding. With monthly blood losses of 240 mL and 420 mL, IV iron dextran remained the most cost-effective strategy, with ICERs of $22,500 per QALY and $10,100 per QALY, respectively.
While IV iron sucrose and IV ferumoxytol achieved similar QALY gains, they were associated with higher total costs due to the requirement for multiple infusions, diminishing their comparative value in the model.
Clinical and Public Health Considerations
Despite evidence supporting the effectiveness of IV iron, treatment delays persist. In the U.S., women with IDA and heavy menstrual bleeding receive their first IV iron infusion an average of 4.4 years after symptom onset and 1.4 years after formal diagnosis.
Wang noted that patients are often undiagnosed or underdiagnosed, living with chronic negative iron balance. He emphasized the importance of identifying effective interventions for iron repletion, especially given the increased iron needs during pregnancy.
The authors highlighted that oral iron intolerance, incomplete absorption, and adherence issues may contribute to prolonged symptoms and reduced quality of life. IV iron formulations are fully absorbed and generally well tolerated, though they carry a small risk of infusion reactions.
Study Limitations and Future Research
Limitations of the study include assumptions of uniform menstrual blood loss throughout the reproductive lifespan and the exclusion of some single-dose IV iron formulations, such as ferric derisomaltose and ferric carboxymaltose. The model also did not account for patients switching between iron therapies or for potential reductions in bleeding after treating underlying gynecologic conditions.
The research team plans to refine the model further and develop tools for patients, clinicians, and administrators to support shared decision-making. Senior author George Goshua, MD, MSc, from Yale School of Medicine, expressed hope that this model could be adapted globally to help decrease insurance barriers and improve decision-making and quality of life for women.