Management of Normal Ferritin with Mildly Low TSAT in Premenopausal Women
In a premenopausal woman with normal ferritin and mildly low TSAT (<20%), you should treat with oral or intravenous iron supplementation, as TSAT <20% is the most reliable indicator of iron deficiency and predicts clinical benefit, regardless of ferritin level. 1, 2, 3
Why TSAT Matters More Than Ferritin
TSAT <20% is a highly sensitive marker for iron deficiency with 75% sensitivity for true iron deficiency, while ferritin <100 ng/mL has only 35-48% sensitivity, making TSAT the superior diagnostic parameter 1
TSAT is less affected by inflammation than ferritin, which is an acute-phase reactant that can be falsely elevated by subclinical inflammation, infection, or other conditions common in premenopausal women 4, 5
Recent evidence from heart failure trials demonstrates that TSAT <20%—not ferritin—predicts who benefits from iron therapy, with patients showing reduced adverse events when TSAT is low regardless of ferritin levels 3, 6
Normal ferritin does not exclude iron deficiency in premenopausal women, as ferritin levels of 20-300 ng/mL lie within the normal range for healthy adults but may still represent inadequate iron availability for erythropoiesis 3
Treatment Algorithm
Step 1: Confirm Iron Deficiency
- Verify TSAT <20% with complete iron panel (serum iron, TIBC, ferritin) 1, 2
- Check CBC to assess for anemia and MCV 1
- Consider inflammatory markers (CRP, ESR) if ferritin is unexpectedly normal or elevated 2
Step 2: Assess for Ongoing Losses
- Evaluate menstrual blood loss (heavy menstrual bleeding is the most common cause in premenopausal women) 1
- Screen for gastrointestinal losses if menstrual history doesn't explain deficiency 1
- Consider malabsorption conditions (celiac disease, autoimmune gastritis, prior bariatric surgery) 1
Step 3: Choose Iron Formulation
For oral iron (first-line if tolerated):
- Prescribe 100-200 mg elemental iron daily on an empty stomach 1
- Expect hemoglobin increase of 1-2 g/dL within 4-8 weeks 1
For intravenous iron (preferred if oral intolerance or ongoing losses):
- Ferric derisomaltose (FDI): 1000 mg infusion or up to 20 mg/kg (max 1500 mg) diluted in 100 mL normal saline 1, 2
- Ferric carboxymaltose (FCM): effective alternative with similar dosing 2
- IV iron is superior when there are ongoing menstrual losses or malabsorption 1
Step 4: Monitor Response
- Recheck iron parameters (CBC, ferritin, TSAT) 4-8 weeks after treatment 1, 2
- Do not check iron studies within 4 weeks of IV iron, as circulating iron interferes with assays 1, 2
- Expect hemoglobin increase within 1-2 weeks and rise of 1-2 g/dL by 4-8 weeks 1
- Goal: TSAT ≥20% and ferritin ≥50 ng/mL in absence of inflammation 1, 2
Critical Pitfalls to Avoid
Do not dismiss low TSAT just because ferritin is "normal"—this represents functional iron deficiency where iron stores cannot be mobilized effectively for erythropoiesis 2, 7, 3
Do not rely solely on ferritin thresholds <30 ng/mL used in general populations; premenopausal women with ongoing menstrual losses may have functional deficiency at higher ferritin levels 1, 3
Avoid measuring iron parameters too soon after IV iron administration (wait 4-8 weeks) as this yields spurious results 1, 2
Consider reticulocyte hemoglobin content (CHr or RET-He) if available, as this directly assesses iron availability for erythropoiesis and is not affected by inflammation 1, 2
Special Considerations for Premenopausal Women
Heavy menstrual bleeding requires ongoing iron supplementation, not just a single course, with frequency dependent on degree of blood loss 1
Routine surveillance of iron status is advisable in women with known heavy menses to detect deficiency early before anemia develops 4, 5
If inadequate response to treatment, reassess for ongoing losses, malabsorption, or consider soluble transferrin receptor (sTfR) testing to confirm true iron deficiency 1, 2