What is the best course of action for a 40-year-old premenopausal woman with low iron levels, normal ferritin, and an Iron Saturation Index indicating iron deficiency?

Iron Deficiency Without Anemia in a Premenopausal Woman

This 40-year-old woman has non-anemic iron deficiency (NAID) based on her low iron saturation index (0.07 or 7%) and low serum iron (4 umol/L), despite normal ferritin (114 ug/L), and she should be started on oral iron supplementation immediately while screening for celiac disease and evaluating for menstrual blood loss as the likely cause. 1

Understanding the Laboratory Pattern

Your patient has functional iron deficiency - her ferritin is normal at 114 ug/L, but her transferrin saturation is critically low at 7% (normal >16-20%), indicating insufficient iron is available for red blood cell production despite adequate storage iron. 1, 2

• The iron saturation index of 0.07 (7%) is well below the critical threshold of 16%, which is a sensitive marker for iron deficiency requiring treatment 2
• Low serum iron (4 umol/L) combined with low transferrin saturation confirms that iron delivery to bone marrow for hemoglobin synthesis is impaired 2
• Ferritin >100 ug/L makes absolute iron deficiency unlikely, but does not exclude functional iron deficiency or early depletion of readily available iron 1, 2

Investigation Strategy for Premenopausal Women

GI investigation is NOT mandatory for this patient unless specific red flags are present. 1

Non-invasive testing should be performed first:

• Screen for celiac disease with tissue transglutaminase antibodies (tTG) - found in 3-5% of iron deficiency cases 1
• Test for H. pylori non-invasively (stool antigen or urea breath test) 1
• Assess menstrual blood loss history - the most common cause in premenopausal women 1

Reserve bidirectional endoscopy for specific situations only:

• Age ≥50 years (higher malignancy risk) 1
• GI symptoms (abdominal pain, change in bowel habits, blood in stool) 1
• Strong family history of colorectal cancer (two first-degree relatives or one affected before age 50) 1
• Positive celiac or H. pylori testing requiring confirmation 1
• Failure to respond to adequate oral iron therapy after 8-10 weeks 1, 2

The overall prevalence of significant GI pathology, particularly malignancy, is low in premenopausal women with NAID in the absence of these red flags. 1

Iron Supplementation Protocol

Start oral iron supplementation immediately - do not wait for investigation results. 1, 2, 3

Dosing regimen:

• Ferrous sulfate 325 mg daily (65 mg elemental iron) OR alternate-day dosing of 60 mg elemental iron 4, 3
• Alternate-day dosing may improve absorption and reduce gastrointestinal side effects compared to daily dosing 2, 5
• Take on empty stomach for optimal absorption; if GI symptoms occur, take with meals 2

Expected side effects and management:

• Constipation, nausea, or diarrhea are common 2
• Switch to alternate-day dosing or take with food if side effects are intolerable 2, 5
• Low-dose preparations (27-50 mg elemental iron) may reduce side effects while maintaining efficacy 6, 5

Follow-Up and Monitoring

Repeat complete blood count and iron studies (including ferritin and transferrin saturation) in 8-10 weeks to assess response. 2, 6, 3

Treatment targets:

• Target ferritin >100 ng/mL to restore iron stores and prevent recurrence 2
• Transferrin saturation should normalize to >20% 2
• Hemoglobin should remain stable or improve if borderline 2

If no improvement after 8-10 weeks, consider:

• Malabsorption (celiac disease, atrophic gastritis, post-bariatric surgery) 3
• Non-compliance with therapy 2
• Ongoing blood loss (occult GI bleeding, heavy menstruation) 3
• Need for intravenous iron 3

Long-Term Management

For patients with recurrent low iron indices (menstruating females, vegetarians, athletes), screen ferritin and transferrin saturation every 6-12 months. 2, 6

• Do not continue daily iron supplementation once ferritin normalizes and transferrin saturation is >20%, as this is potentially harmful 2, 6
• Counsel on iron-rich diet including heme iron sources (meat, poultry, fish) and non-heme iron with vitamin C enhancers 6
• Address underlying causes: treat menorrhagia if present, optimize dietary intake, consider intermittent oral supplementation to maintain stores 6, 7

Critical Pitfalls to Avoid

Do not assume normal ferritin excludes iron deficiency - transferrin saturation is the key parameter for assessing iron availability for erythropoiesis, and low TSAT with normal ferritin indicates functional iron deficiency. 2

Do not perform extensive GI investigation in young, asymptomatic premenopausal women with heavy menses - the yield is extremely low (0-6.5%) and menstrual blood loss is the overwhelmingly likely cause. 1

Do not overlook celiac disease - it is present in 3-5% of iron deficiency cases and is easily missed without serologic screening. 1