What is the evaluation and treatment approach for a premenopausal woman with iron deficiency anemia, characterized by low ferritin levels?

Evaluation and Management of Premenopausal Women with Iron Deficiency Anemia and Low Ferritin

For premenopausal women with iron deficiency anemia (hemoglobin <12 g/dL and ferritin <45 ng/mL), start empiric oral iron supplementation immediately and perform non-invasive testing for H. pylori and celiac disease, reserving bidirectional endoscopy only for those with GI symptoms, positive testing, failure to respond to iron therapy, or age ≥50 years. 1

Diagnostic Confirmation

Confirm iron deficiency anemia using:

• Hemoglobin <12 g/dL in non-pregnant women 1
• Ferritin <45 ng/mL (sensitivity 85%, specificity 92%) 1
• Note that ferritin is an acute-phase reactant and may be falsely elevated in inflammatory conditions, chronic kidney disease, or tissue damage 1, 2

Initial Non-Invasive Evaluation

All asymptomatic premenopausal women with iron deficiency anemia should receive:

• Non-invasive H. pylori testing (stool antigen or urea breath test) 1
• Celiac disease serologic testing (tissue transglutaminase antibodies) 1
• Detailed menstrual history to assess for heavy menstrual bleeding as the most common cause 3, 4

If either test is positive, treat the underlying condition accordingly before proceeding with further evaluation 1.

Endoscopy Decision Algorithm

The AGA provides conditional (not strong) recommendations for bidirectional endoscopy in premenopausal women, acknowledging that younger women with plausible explanations (heavy menses) may reasonably choose empiric iron supplementation alone. 1

Reserve bidirectional endoscopy for:

• GI symptoms (abdominal pain, change in bowel habits, blood in stool) 1
• Positive H. pylori or celiac testing requiring endoscopic confirmation 1
• Failure to respond to adequate oral iron therapy after 8-10 weeks 1
• Age ≥50 years (higher risk of GI malignancy) 1
• Strong family history of colorectal cancer 1

Avoid routine endoscopy in:

• Young premenopausal women with heavy menstrual bleeding and no GI symptoms 1
• Those who prioritize avoiding endoscopy risks over detecting rare neoplasia in this low-risk population 1

This approach is supported by the very low yield (0-6.5%) of significant GI pathology in young, asymptomatic premenopausal women with heavy menses 2.

Iron Supplementation Protocol

Start oral iron immediately without waiting for investigation results:

• Ferrous sulfate 325 mg daily (65 mg elemental iron) OR ferrous bisglycinate 30-60 mg elemental iron 2, 5, 3
• Alternate-day dosing (60 mg every other day) may improve absorption and reduce GI side effects compared to daily dosing 2, 5
• Take on empty stomach for optimal absorption, or with meals if GI symptoms occur 2
• Expected side effects include constipation, nausea, or diarrhea (50% of patients have decreased adherence) 2, 5

Follow-Up and Response Assessment

Repeat CBC and ferritin in 8-10 weeks (or evaluate hemoglobin response in 2-4 weeks):

• Target ferritin >100 ng/mL to restore iron stores and prevent recurrence 1, 2
• Expected hemoglobin rise of 1-2 g/dL after 2-4 weeks indicates adequate response 5

If no improvement after 8-10 weeks, consider:

• Malabsorption (celiac disease, atrophic gastritis, post-bariatric surgery) 5, 3
• Non-compliance due to side effects 5
• Ongoing blood loss requiring investigation 5, 3
• Switch to intravenous iron for intolerance or inadequate response 5, 3

Intravenous Iron Indications

Consider IV iron for:

• Oral iron intolerance or poor absorption 5, 3
• Ongoing blood loss that cannot be controlled 3
• Chronic inflammatory conditions (IBD, CKD, heart failure) 3
• Second and third trimesters of pregnancy 3
• Failure to respond to adequate oral iron trial 5, 3

Hypersensitivity to newer IV iron formulations is rare (<1%) 5.

Long-Term Monitoring

For patients with recurrent low ferritin:

• Screen ferritin every 6-12 months in high-risk groups (menstruating females, vegetarians, athletes, regular blood donors) 2
• Do not continue daily iron supplementation once ferritin normalizes, as this is potentially harmful 2

Critical Pitfalls to Avoid

• Do not perform extensive GI investigation in young, asymptomatic premenopausal women with heavy menses without red flags—the yield is extremely low 1, 2
• Do not overlook celiac disease screening—it is present in 3-5% of iron deficiency cases and easily missed without serologic testing 2
• Do not assume normal ferritin excludes iron deficiency in inflammatory states—ferritin can be falsely elevated, and transferrin saturation <20% may be more reliable 2
• Do not delay iron supplementation while awaiting investigation results—start treatment immediately 2