What is the best course of treatment for a premenopausal woman with low ferritin (iron storage) levels, indicating iron deficiency anemia?

Treatment of Low Ferritin in Premenopausal Women

Start oral iron supplementation immediately with ferrous sulfate 325 mg (65 mg elemental iron) daily or every other day, and investigate the underlying cause based on age and symptoms. 1

Immediate Treatment Approach

All patients with low ferritin require iron supplementation to correct deficiency and replenish body stores, regardless of hemoglobin level. 1

Iron Supplementation Protocol

• Ferrous sulfate 200-325 mg (containing 65 mg elemental iron) is the first-line, most cost-effective option 1, 2
• Alternate-day dosing (every other day) may improve absorption and reduce gastrointestinal side effects compared to daily dosing 3, 4
• Take on an empty stomach for optimal absorption; if gastrointestinal symptoms occur (constipation, nausea, diarrhea), take with meals 3
• Continue iron supplementation for 3 months after correction of anemia to replenish iron stores 1
• Ascorbic acid (vitamin C) enhances iron absorption and should be considered when response is poor 1

Expected Response and Monitoring

• Hemoglobin should rise by 2 g/dL after 3-4 weeks of treatment 1
• Repeat CBC and ferritin in 8-10 weeks to assess response 5, 3
• Target ferritin >100 ng/mL to restore iron stores and prevent recurrence 6
• Failure to respond indicates poor compliance, misdiagnosis, continued blood loss, or malabsorption 1

Investigation Strategy: Age-Based Algorithm

The 2020 AGA guidelines provide the most recent evidence-based approach, distinguishing between premenopausal women based on age and symptoms. 1

For Premenopausal Women Under Age 45

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

Initial Non-Invasive Testing (Perform First):

• Test for celiac disease with tissue transglutaminase antibodies (tTG) and IgA level (celiac disease causes 3-5% of iron deficiency cases) 1
• Non-invasive H. pylori testing (stool antigen or urea breath test) 1
• Assess menstrual blood loss history—the most common cause in this population 1

Reserve Bidirectional Endoscopy For:

• Upper GI symptoms (dyspepsia, reflux, abdominal pain) 1
• Positive celiac or H. pylori testing requiring confirmation 1
• Failure to respond to adequate oral iron therapy after 8-10 weeks 1, 3
• New or worsening GI symptoms (change in bowel habits, blood in stool) 1

For Premenopausal Women Age 45 and Older

The AGA recommends bidirectional endoscopy (upper endoscopy with small bowel biopsy AND colonoscopy) due to increasing incidence of GI malignancy with age. 1

• This is a conditional recommendation based on moderate quality evidence 1
• Patients who place high value on avoiding endoscopy risks and have plausible causes (heavy menses) may reasonably choose initial iron replacement only 1

Diagnostic Thresholds for Iron Deficiency

Understanding ferritin cutoffs is critical, as the 2020 AGA guidelines updated traditional thresholds. 1

• Ferritin <45 ng/mL is the recommended diagnostic cutoff (strong recommendation, high-quality evidence, specificity 0.92) 1
• Ferritin <15 ng/mL has 99% specificity for absolute iron deficiency 1, 6
• Ferritin 15-30 ng/mL indicates low body iron stores and warrants treatment 6
• This represents a significant change from older guidelines using <15 ng/mL cutoffs 1

Critical Caveat: Rule Out Inflammation

• Ferritin is an acute-phase reactant that rises during inflammation, infection, or tissue damage, potentially masking true iron deficiency 6, 5
• In inflammatory conditions, ferritin thresholds shift upward to <100 ng/mL 6
• Check CRP or ESR if ferritin is 30-100 ng/mL to exclude falsely elevated ferritin 6

When to Use Intravenous Iron

Parenteral iron should be reserved for specific situations, as it is expensive, carries anaphylaxis risk, and provides no faster hemoglobin rise than oral iron. 1

Indications for IV Iron:

• Intolerance to at least two oral iron preparations 1
• Malabsorption (celiac disease, post-bariatric surgery, inflammatory bowel disease) 3
• Chronic inflammatory conditions (CKD, heart failure, IBD, cancer) 3
• Ongoing blood loss requiring rapid repletion 3
• Second and third trimesters of pregnancy 3

Long-Term Management for Recurrent Iron Deficiency

For patients with recurrent low ferritin (menstruating females, vegetarians, athletes), screen ferritin every 6-12 months. 6, 5

• Do NOT continue daily iron supplementation once ferritin normalizes, as this is potentially harmful 6, 5
• Consider intermittent oral iron to preserve stores in high-risk populations 5

Common Pitfalls to Avoid

• Do not assume normal hemoglobin excludes iron deficiency—low ferritin alone causes fatigue, exercise intolerance, and reduced quality of life even without anemia 6, 5, 3
• Do not perform extensive GI investigation in young, asymptomatic premenopausal women with heavy menses—the yield for serious pathology is extremely low (0-6.5%) 1
• Do not overlook celiac disease—it is present in 3-5% of iron deficiency cases and easily missed without serologic screening 1
• Do not ignore treatment failure—lack of response after 8-10 weeks mandates investigation for malabsorption, ongoing blood loss, or need for IV iron 1, 3