How should I evaluate and treat a 52-year-old woman with fatigue and a ferritin level of 18 ng/mL?

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Evaluation and Management of a 52-Year-Old Woman with Fatigue and Ferritin 18 ng/mL

This patient has iron deficiency anemia that requires immediate oral iron supplementation and investigation for the underlying cause of iron loss.

Confirming the Diagnosis

Your patient's ferritin of 18 ng/mL is definitively diagnostic of iron deficiency. 1 A ferritin <30 ng/mL confirms depleted iron stores in the absence of inflammation, and even in the presence of inflammation, a ferritin <45 ng/mL has 85% sensitivity and 92% specificity for iron deficiency. 1

Check transferrin saturation (TSAT) simultaneously with ferritin to complete the iron panel. 1 In true iron deficiency, you should expect TSAT <20%. 1, 2 This combination (ferritin <30 ng/mL + TSAT <20%) provides the highest diagnostic certainty. 3

Order a complete blood count (CBC) to assess hemoglobin and mean corpuscular volume (MCV). 2 The fatigue suggests she likely has iron deficiency anemia, not just iron deficiency without anemia. Expect microcytic anemia (low MCV) if the deficiency is longstanding, though early iron deficiency may present with normocytic anemia. 4

Immediate Treatment

Start oral ferrous sulfate 325 mg daily or every other day immediately. 2, 3 Every-other-day dosing improves absorption and reduces gastrointestinal side effects, which affect approximately 50% of patients and decrease adherence. 3 Taking the tablets with meals further limits side effects. 5

Continue iron supplementation for at least 3 months after hemoglobin normalizes—typically 6 months total—to fully replenish iron stores. 5, 3 The target is ferritin >100 ng/mL and TSAT >20%. 1 Premature discontinuation leads to rapid recurrence. 5

Recheck CBC, ferritin, and TSAT in 2-4 weeks to confirm response. 3 Hemoglobin should rise by approximately 1 g/dL every 2-3 weeks with adequate oral iron therapy. If there is no response, consider intravenous iron or investigate malabsorption. 3

Investigating the Underlying Cause

In a 52-year-old postmenopausal woman, iron deficiency is abnormal and demands investigation for gastrointestinal blood loss. 1 Recurrent blood loss accounts for 94% of iron deficiency cases. 3

Mandatory Gastrointestinal Evaluation

Perform bidirectional endoscopy (esophagogastroduodenoscopy and colonoscopy) to evaluate for occult gastrointestinal bleeding. 1 The AGA strongly recommends bidirectional endoscopy in asymptomatic postmenopausal women with iron deficiency anemia, as this population has high rates of gastrointestinal malignancy and other significant pathology. 1

Test for Helicobacter pylori infection and celiac disease with noninvasive testing (serology). 3 Both are common, treatable causes of iron deficiency. Check tissue transglutaminase (TTG) antibodies for celiac disease. 3

Additional History to Obtain

  • Detailed menstrual history: Confirm she is truly postmenopausal. Heavy menstrual bleeding is the most common cause of iron deficiency in premenopausal women. 2
  • Medication use: NSAIDs cause gastrointestinal blood loss. 2 Proton pump inhibitors and H2-blockers impair iron absorption. 2
  • Dietary history: Vegetarian or vegan diets may provide inadequate dietary iron. 1
  • Prior gastric surgery: Bariatric procedures (gastric bypass, sleeve gastrectomy) impair iron absorption. 2, 3
  • Chronic inflammatory conditions: Inflammatory bowel disease, chronic kidney disease, heart failure, and cancer are associated with iron deficiency. 2
  • Blood donation history: Frequent blood donation depletes iron stores. 1

When to Consider Intravenous Iron

Switch to intravenous iron if:

  • Oral iron is not tolerated despite every-other-day dosing. 2, 3
  • No hemoglobin response after 2-4 weeks of adequate oral therapy. 3
  • Malabsorption is documented (celiac disease, post-bariatric surgery). 2, 3
  • Ongoing blood loss that cannot be immediately controlled. 2
  • Coexisting chronic inflammatory conditions (IBD, CKD, heart failure). 2, 3

Hypersensitivity to newer intravenous iron formulations is rare (<1%). 3

Critical Pitfalls to Avoid

Do not assume menopause explains the iron deficiency. 1 Postmenopausal women should not be iron deficient from physiologic causes alone. Gastrointestinal pathology must be excluded. 1

Do not stop iron supplementation when hemoglobin normalizes. 5 Continue for 6 months total to replenish tissue iron stores and prevent rapid recurrence. 5

Do not overlook celiac disease and H. pylori. 3 These are common, treatable causes that will lead to recurrent iron deficiency if not addressed. 3

Do not use ferritin alone to monitor treatment response. 1 Always check TSAT simultaneously, as ferritin can be falsely elevated by inflammation even when iron stores remain depleted. 1

Expected Clinical Course

With appropriate oral iron therapy, her fatigue should begin improving within 2-4 weeks as hemoglobin rises. 3 Full symptom resolution typically occurs once hemoglobin normalizes, usually by 8-12 weeks. 5 If fatigue persists despite hemoglobin normalization, consider alternative causes such as thyroid dysfunction, vitamin B12 deficiency, or sleep disorders. 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Iron Deficiency Anemia: Evaluation and Management.

American family physician, 2025

Research

Iron deficiency anemia. Every case is instructive.

Postgraduate medicine, 1993

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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