Iron-deficiency anemia in premenopausal women: A comparative study of menstrual blood loss and malabsorptive etiologies

Abstract

Abstract Introduction Intestinal iron malabsorption refers to the impaired uptake of dietary iron across the gastrointestinal mucosa, most commonly affecting the duodenum and proximal jejunum sites critical for iron absorption. This dysfunction can result from a range of conditions, including celiac disease, inflammatory bowel disease, chronic atrophic gastritis, and autoimmune disorders such as pernicious anemia. Although gynecologic causes are frequently implicated in iron-deficiency anemia (IDA) among premenopausal women, malabsorption syndromes remain an underrecognized contributor. Notably, studies estimate that gastrointestinal malabsorption is responsible for 6% to 30% of iron deficiency anemia (IDA) cases in this population. Among these conditions, pernicious anemia is a significant cause, with a global prevalence of 0.1% in the general population and up to 3% in individuals over 60. By impairing vitamin B12 absorption and reducing gastric acid secretion necessary for iron solubilization, it contributes to both megaloblastic and iron-deficiency anemia. This study aims to investigate and compare two distinct etiologies of IDA, heavy menstrual bleeding and confirmed malabsorptive disorders, to assess differences in anemia severity, treatment response, and clinical outcomes. By focusing on the clinical impact of intestinal iron malabsorption, this study seeks to enhance diagnostic accuracy and inform more targeted treatment strategies, particularly for cases of treatment-resistant anemia in premenopausal women. Methods We conducted a retrospective comparative study involving 495 premenopausal women aged 18 to 50 years with confirmed iron-deficiency anemia (IDA), defined as hemoglobin levels below 12 g/dL. Participants were divided into two groups: (1) a control group (n=414) consisting of patients with heavy menstrual bleeding-related IDA, and (2) a case group (n=81) comprising patients with IDA secondary to malabsorption, including pernicious anemia, post-gastrectomy states, inflammatory bowel disease (IBD), and related gastrointestinal disorders. All patients received intravenous iron therapy (Venofer) in combination with oral iron supplementation. In the malabsorption group, vitamin B12 supplementation was administered when indicated. Hemoglobin levels at presentation, anemia stratification, and post-treatment normalization rates were evaluated and compared between groups. Results The malabsorption group, representing 16% prevalence of the total cohort, was disproportionately represented in mild and moderate anemia cases, accounting for 18% and 19% of those subgroups, respectively. In contrast, its contribution to severe and life-threatening anemia was lower, at 13% and 9%. This distribution indicates a tendency toward less severe anemia among patients with malabsorption-related etiologies. Among those with mild anemia (n=33), the most common causes were pernicious anemia (n=12) and post-gastrectomy states (n=4). Moderate anemia (n=36) was primarily associated with post-gastrectomy (n=13), inflammatory bowel disease (n=6), and pernicious anemia (n=5). Severe anemia (n=10) was also predominantly linked to post-gastrectomy (n=7), while the two life-threatening cases were attributed to unknown or other causes. Conclusion These results show that among the 81 patients, 22.2% had pernicious anemia and 29.6% had a history of post-gastrectomy, which were the most predominant underlying causes, suggesting that malabsorption-related anemia may follow a more indolent course. These findings highlight the importance of heightened clinical vigilance and routine screening for malabsorption syndromes in patients presenting with unexplained mild to moderate anemia. Further research is warranted to investigate the mechanisms driving this pattern and to evaluate the impact of early diagnosis and targeted treatment on long-term outcomes.