Revisiting Ferritin Reference Ranges: A Case for Addressing Iron Deficiency in Women with Symptom-Driven Standards

Abstract

Iron deficiency (ID), even without anemia, is an insidious condition which reduces quality of life through diverse symptoms. Women are particularly susceptible due to menstruation, pregnancy, and childbirth, resulting in nearly 1 in 5 affected under current thresholds. ID is typically investigated when ferritin levels are below the lower limit of normal (LLN.) Apart from fatigue, many symptoms like hair loss, restless leg syndrome (RLS), angular cheilitis, and impaired cognition are rarely evaluated, furthering dependence on ferritin values for diagnosis. Foundational studies defining normal ferritin did not screen for symptoms or risk factors of ID, resulting in iron-deficient women in control groups. This has led to an erroneously low mean LLN of 9ng/mL for females amongst the five most used commercial laboratories. Many specialty societies and national guidelines target ferritin >30ng/ml for both sexes due to evidence of clinical ID below this level. A 31-year-old woman with a history of three pregnancies all requiring postpartum iron supplementation presented with fatigue, palpitations, and restless legs. She did not endorse pica, reflux, or nail changes. Her menstrual cycles are four days, regular, and include occasional penny-sized clots. Testing revealed normal hemoglobin and a ferritin of 22ng/ml (normal 10-106ng/ml). She was started on oral iron with a goal of ferritin >75ng/ml as per Sleep Medicine RLS treatment guidelines. At initial follow-up, fatigue was already markedly reduced with her ferritin up to 30ng/ml, a 36% increase. New reference ranges for ferritin with LLNs of at least 30ng/mL are required to better facilitate early diagnosis of ID, especially in high risk groups like menstruating women. Current ferritin reference ranges are bred from inappropriate studies that exclude symptoms and risk factors necessary to characterize ID. By redefining normal ferritin ranges, women can better receive care for symptoms that have perennially gone untreated.