What is the best treatment for a premenopausal woman with iron deficiency but without anemia?

Treatment of Iron Deficiency Without Anemia in Premenopausal Women

In premenopausal women with iron deficiency but without anemia, oral iron supplementation is recommended to replenish iron stores and prevent progression to anemia, as the cause is most likely menstrual blood loss, and gastrointestinal investigation is generally not warranted in the absence of other risk factors. 1

Initial Management Approach

Start oral ferrous sulfate 200 mg once daily (containing 65 mg elemental iron) immediately to replenish depleted iron stores before anemia develops. 1, 2, 3 This once-daily dosing improves tolerability while maintaining effective iron absorption. 2

Key Treatment Points:

• Continue iron therapy for 3 months after ferritin normalizes to fully replenish body iron stores, not just until symptoms resolve. 1, 2
• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption, particularly important when ferritin is very low. 1, 2
• Alternative formulations (ferrous gluconate or ferrous fumarate) are equally effective if ferrous sulfate causes intolerable gastrointestinal side effects. 1, 2

Investigation Strategy

The threshold for gastrointestinal investigation should be low in men and postmenopausal women, but generally is not warranted in premenopausal women since the cause is likely menstrual blood loss and/or recent pregnancy. 1 The overall prevalence of significant underlying GI pathology, and particularly GI malignancy, is low in non-anemic iron deficiency (NAID). 1

When to Investigate Further:

• Screen for celiac disease with antiendomysial antibody (and IgA measurement to exclude IgA deficiency), as it is found in 3-5% of cases and is a common cause of iron deficiency in premenopausal women. 1
• Consider upper GI endoscopy only if the patient has upper GI symptoms (dyspepsia, dysphagia, persistent nausea/vomiting). 1
• Reserve colonoscopy for those with lower GI symptoms, strong family history of colorectal cancer (two affected first-degree relatives or one before age 50), or persistent iron deficiency after supplementation and correction of menstrual losses. 1
• Age ≥50 years warrants full GI investigation even in premenopausal women, as age is the strongest predictor of pathology. 1

Monitoring Protocol

• Check ferritin levels at 4 weeks to assess response to oral iron therapy. 2
• Monitor hemoglobin and red cell indices every 3 months for the first year, then again after another year. 1, 2
• Further investigation is only necessary if iron stores cannot be maintained with supplementation. 1

When to Consider Intravenous Iron

Switch to IV iron if the patient meets any of these criteria:

• Intolerance to at least two different oral iron preparations despite trying ferrous sulfate, ferrous gluconate, and ferrous fumarate. 1, 2
• Failure of ferritin levels to improve after 4 weeks of compliant oral therapy. 2
• Conditions affecting iron absorption (active inflammatory bowel disease, celiac disease with ongoing gluten exposure, post-bariatric surgery). 2
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity. 2

Critical Pitfalls to Avoid

• Do not prescribe multiple daily doses of oral iron—once-daily dosing is superior because hepcidin elevation blocks further absorption for 48 hours. 2
• Do not stop iron therapy when symptoms improve—continue for 3 months after ferritin normalizes to replenish stores. 1, 2
• Do not overlook vitamin C supplementation when oral iron response is suboptimal, as it significantly enhances absorption. 1, 2
• Do not pursue extensive GI investigation in young, asymptomatic premenopausal women without other risk factors, as the yield is extremely low and menstrual loss is the likely cause. 1
• Do not fail to address the underlying cause—evaluate for menorrhagia using pictorial blood loss assessment charts (80% sensitivity and specificity), and consider gynecologic management if excessive menstrual bleeding is confirmed. 1

Special Considerations

Assess menstrual blood loss first, as menorrhagia, pregnancy, and breastfeeding are responsible for iron deficiency in 5-10% of menstruating women. 1, 2 History alone is unreliable for quantifying menstrual loss, so pictorial blood loss assessment charts should be used. 1

Screen for dietary insufficiency, particularly in vegetarians or those with restricted diets, as this is a common contributing factor in premenopausal women. 1, 4