How to manage anemia in a patient on hormone replacement therapy with low hemoglobin, hematocrit, and red blood cell counts?

Management of Low Hemoglobin, Hematocrit, and RBC in AMAB Patients on Hormone Therapy

In an assigned-male-at-birth (AMAB) patient on feminizing hormone therapy with anemia, you should first conduct a complete workup including iron studies, B12, folate, and peripheral smear to identify correctable causes, then treat any identified deficiencies before considering the anemia as an expected physiological response to estrogen therapy. 1, 2

Initial Diagnostic Workup

The evaluation must systematically exclude reversible causes before attributing anemia to hormone effects:

• Obtain iron studies (ferritin, transferrin saturation, serum iron) to assess for functional or absolute iron deficiency 1, 2
• Check vitamin B12 and folate levels to identify nutritional deficiencies 1, 2
• Review peripheral blood smear to evaluate red cell morphology and exclude hemolysis or other pathology 1
• Assess renal function (creatinine, eGFR) since chronic kidney disease commonly causes anemia 2
• Measure reticulocyte count to determine if bone marrow is responding appropriately 2
• Review medication history thoroughly for drugs that may suppress erythropoiesis or cause blood loss 1

Treatment Algorithm Based on Findings

If Iron Deficiency is Identified (Ferritin <100 ng/mL or Transferrin Saturation <20%)

• Initiate oral iron supplementation with ferrous sulfate 200 mg three times daily 1
• Continue iron therapy for 3 months after hemoglobin correction to replenish body stores 1
• Consider adding ascorbic acid if response to oral iron is poor, as it enhances absorption 1
• Use parenteral iron only if the patient cannot tolerate or absorb oral preparations 1
• Monitor ferritin every 3 months during initial treatment 3

If B12 or Folate Deficiency is Present

• Replace the deficient vitamin before proceeding with other interventions 1
• Recheck hemoglobin 4-6 weeks after initiating replacement to assess response 2

If Chronic Kidney Disease is Contributing (GFR <30 mL/min/1.73 m²)

• Check hemoglobin at least every 3 months for ongoing monitoring 1
• Ensure iron stores are adequate first (ferritin >100 ng/mL, transferrin saturation >20%) before considering erythropoietin 2
• Consider erythropoietin therapy only if anemia persists despite iron repletion and hemoglobin remains <10 g/dL 1, 2

If No Correctable Cause is Found

This is the most likely scenario in AMAB patients on feminizing hormones, as estrogen physiologically suppresses erythropoiesis:

• Accept lower hemoglobin targets consistent with cisgender female reference ranges (12-16 g/dL rather than 13.5-17.5 g/dL) 1
• Monitor hemoglobin every 3-6 months to ensure stability and exclude progressive decline 1
• Avoid unnecessary interventions like erythropoietin in asymptomatic patients with stable mild anemia 2

Critical Safety Considerations

Do not initiate erythropoiesis-stimulating agents (ESAs) without clear indication, as they carry significant risks:

• ESAs increase thromboembolism risk, which is already elevated in patients on estrogen therapy 1
• ESAs should never be used to achieve hemoglobin >12 g/dL, as higher targets increase mortality 1, 2
• Uncontrolled hypertension is a contraindication to ESA therapy 2

Transfusion Thresholds

Reserve transfusion for severe symptomatic anemia or hemodynamic instability:

• Consider transfusion if hemoglobin <7.5 g/dL with symptoms (fatigue, dyspnea, chest pain, tachycardia) 2
• Transfuse 2-3 units of packed red blood cells if indicated, expecting each unit to raise hemoglobin by approximately 1.5 g/dL 2
• Avoid transfusion in stable, asymptomatic patients with mild anemia 2, 4

Common Pitfalls to Avoid

• Do not assume anemia is solely due to hormone therapy without excluding iron deficiency, B12/folate deficiency, renal disease, or occult blood loss 1, 5
• Do not target cisgender male hemoglobin ranges in AMAB patients on feminizing hormones, as this may lead to unnecessary and potentially harmful interventions 1
• Do not continue iron supplementation indefinitely without monitoring, as this can lead to iron overload 1, 3
• Do not use ESAs as first-line therapy without correcting nutritional deficiencies and ensuring adequate iron stores 1, 2