In an adult male on testosterone replacement therapy who previously required therapeutic phlebotomy for testosterone‑induced erythrocytosis and now has iron‑deficiency anemia (low ferritin, low transferrin saturation, high total iron‑binding capacity), should I be treated with oral iron supplementation or intravenous iron infusion?

Iron Supplementation in Testosterone-Induced Erythrocytosis with Iron Deficiency

You should receive iron supplementation—specifically intravenous iron—to correct your iron deficiency anemia, despite your history of testosterone-induced erythrocytosis requiring phlebotomy. 1

Why Iron Replacement Is Necessary

Your laboratory findings (low ferritin, low iron saturation, elevated TIBC and transferrin) definitively indicate absolute iron deficiency anemia, which requires treatment regardless of your testosterone therapy status. 2, 1

• Iron deficiency increases stroke risk: Even in patients with elevated hemoglobin from other causes, iron-deficient red blood cells have reduced oxygen-carrying capacity and decreased deformability (microcytes), which paradoxically increases thrombotic risk including stroke. 2

• Therapeutic phlebotomy depletes iron stores: Your previous phlebotomy treatments for testosterone-induced erythrocytosis have directly caused your current iron deficiency by removing iron-containing red blood cells. 2, 3

• Iron deficiency worsens outcomes: Leaving iron deficiency untreated prolongs anemia-related symptoms (fatigue, reduced exercise capacity, cognitive decline) and creates a more dangerous clinical situation than appropriately managed erythrocytosis. 1

Intravenous Iron Is Preferred Over Oral Iron

Intravenous iron should be your first-line treatment based on your clinical scenario. 1

Reasons favoring IV iron:

• Prior IV iron use: You have already received ferrlecit (sodium ferric gluconate) infusions previously, demonstrating tolerance to intravenous formulations. 1

• Superior efficacy: Only 21% of patients who fail oral iron respond to continued oral therapy, whereas approximately 65% respond when switched to intravenous iron. 1

• Testosterone-mediated iron flux: Testosterone suppresses hepcidin and increases iron mobilization, which may interfere with oral iron absorption but allows IV iron to directly replenish stores. 4, 5

• Rapid repletion needed: Your severely depleted iron parameters (low ferritin and iron saturation with elevated TIBC) require efficient restoration to prevent complications. 1

Specific IV iron formulation recommendations:

Ferric carboxymaltose (Ferinject/Injectafer) is the preferred option because it can deliver 1000 mg in a single 15-minute infusion with a treatment-related adverse event rate of only 2.7%. 2, 1, 6

Alternative formulations include:

• Iron sucrose (Venofer): 200 mg over 10 minutes, requiring multiple doses 2, 7
• Low-molecular-weight iron dextran (Cosmofer): Can deliver full repletion dose in single infusion but requires test dose due to anaphylaxis risk 2, 1

If You Choose Oral Iron Instead

If you prefer oral iron despite the lower efficacy, use ferrous sulfate 200 mg every other day rather than daily dosing. 2, 8

• Every-other-day dosing improves absorption and reduces gastrointestinal side effects that cause 50% of patients to discontinue oral iron. 8

• Monitor closely: Testosterone administration can cause rapid increases in hemoglobin when combined with oral iron, requiring hemoglobin monitoring every 2-4 weeks initially. 2, 8

• Expect slower response: Oral iron takes 3 months to replenish stores after correcting anemia, versus 8-10 weeks with IV iron. 2, 1

Critical Monitoring Plan

Immediate laboratory reassessment (8-10 weeks after IV iron):

• Hemoglobin, hematocrit, ferritin, iron saturation, TIBC 1
• Target goals: Hemoglobin increase of 1-2 g/dL, ferritin >100 ng/mL, transferrin saturation >20% 2, 1

Ongoing surveillance while on testosterone:

• Hemoglobin and hematocrit every 3 months to detect recurrent erythrocytosis 2
• Ferritin and iron studies every 3 months for 1 year, then annually if stable 2, 1

Thresholds requiring intervention:

• Hemoglobin >20 g/dL or hematocrit >65% with hyperviscosity symptoms: Consider therapeutic phlebotomy with volume replacement 2
• Recurrent iron deficiency: Repeat IV iron supplementation as needed 1

Addressing the Underlying Cause

Investigate why iron deficiency developed beyond phlebotomy alone:

• Gastrointestinal evaluation: Bidirectional endoscopy is recommended in men with iron deficiency to exclude occult bleeding sources. 2, 8

• Helicobacter pylori testing: This infection causes iron malabsorption and should be ruled out with noninvasive testing. 1, 8

• Celiac disease screening: Tissue transglutaminase antibodies should be checked, as celiac disease is present in up to 4% of patients with iron deficiency anemia. 1, 8

Managing Testosterone Therapy Going Forward

Do not discontinue testosterone solely because of this iron deficiency episode, but optimize your regimen:

• Testosterone dose adjustment: Work with your prescriber to use the lowest effective testosterone dose that maintains therapeutic benefit while minimizing erythrocytosis risk. 3

• Avoid routine prophylactic phlebotomy: Repeated phlebotomies deplete iron stores and increase stroke risk; reserve phlebotomy only for hemoglobin >20 g/dL with symptoms. 2, 3

• Recognize the mechanism: Testosterone suppresses hepcidin (the master iron regulator), increases erythropoietin, and mobilizes iron into red blood cells—this is why you developed erythrocytosis initially and why iron deficiency is particularly problematic in this context. 4, 5

Common Pitfall to Avoid

Do not withhold iron replacement due to fear of worsening erythrocytosis. Iron-deficient erythrocytosis is more dangerous than iron-replete erythrocytosis because microcytic red blood cells have reduced deformability and oxygen-carrying capacity, increasing thrombotic risk. 2, 1 The appropriate strategy is to correct iron deficiency while monitoring hemoglobin closely and adjusting testosterone dosing if needed.