How do hemoglobin (Hb) and hematocrit (Hct) measurements compare in patients undergoing testosterone replacement therapy (TRT)?

From the Guidelines

When monitoring patients on testosterone replacement therapy, hematocrit should be the primary safety parameter, with a target to maintain levels below 54%, as levels above this threshold increase cardiovascular risk, as indicated by the most recent guideline 1. The measurement of both hemoglobin and hematocrit is crucial in patients undergoing testosterone replacement therapy.

• Hematocrit is the key safety parameter due to its direct relationship with blood viscosity and cardiovascular risk.
• Hemoglobin provides complementary information about oxygen-carrying capacity but is not as directly tied to safety thresholds as hematocrit. The mechanism behind elevated levels involves testosterone's stimulation of erythropoiesis in bone marrow, increasing red blood cell production, as noted in earlier studies 1. Baseline measurements should be taken before starting testosterone therapy, followed by monitoring at 3-6 month intervals during the first year, and then annually thereafter.
• If hematocrit rises above 54%, testosterone therapy should be temporarily discontinued until levels normalize, then resumed at a lower dose, according to the 2018 guideline 1. Patients should be advised to stay well-hydrated before blood tests, as dehydration can artificially elevate hematocrit values. Those with persistently high levels despite dose adjustments may require therapeutic phlebotomy or consideration of alternative testosterone formulations that produce smaller increases in hematocrit, as suggested by the evaluation and management of testosterone deficiency guideline 1.

From the FDA Drug Label

5.3 Polycythemia Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events.

Hemoglobin vs Hematocrit Measurement:

• Both hematocrit and hemoglobin levels should be monitored in patients undergoing testosterone replacement therapy.
• Hematocrit is checked prior to initiating treatment, and then re-evaluated 3 to 6 months after starting treatment, and then annually.
• If hematocrit becomes elevated, therapy should be stopped until it decreases to an acceptable concentration.
• Increases in red blood cell mass, reflected by increases in hematocrit, may require lowering or discontinuation of testosterone.
• Monitoring of hemoglobin levels is also important, as increases in red blood cell mass may increase the risk of thromboembolic events 2.

From the Research

Hemoglobin vs Hematocrit Measurement on Testosterone Replacement

• Hemoglobin and hematocrit levels are closely monitored in patients undergoing testosterone replacement therapy (TRT) due to the risk of polycythemia and subsequent vascular events 3, 4.
• Studies have shown that TRT can lead to significant increases in hemoglobin and hematocrit levels, with some patients experiencing levels above the recommended threshold 3, 5.
• The relationship between hemoglobin and hematocrit levels and the risk of major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE) has been investigated, with results suggesting that secondary polycythemia in men receiving TRT increases the risk of MACE and VTE in the first year of therapy 6.
• Different routes of testosterone administration may influence the extent of hematocrit increases, with injectables tend to produce the greatest effect 4, 7.
• Monitoring of hemoglobin and hematocrit levels is crucial in patients undergoing TRT, and adjustments to treatment may be necessary to minimize the risks of polycythemia and subsequent vascular events 3, 5, 7.

Key Findings

• A study of male blood donors on TRT found that hemoglobin concentrations were elevated in donors on TRT, and significant numbers had hemoglobin levels above those recommended by current guidelines 3.
• A literature review on erythrocytosis and polycythemia secondary to TRT found that men undergoing TRT have a 315% greater risk for developing erythrocytosis (defined as Hct > 0.52) when compared with control 4.
• A narrative review on the management of hematocrit levels for testosterone replacement patients found that elevations in hematocrit levels triggered by testosterone therapy seem to be controversial, with some studies advocating noninferior effects as compared to placebo while others found adverse side effects on cardiovascular health 5.
• A study on secondary polycythemia in men receiving testosterone therapy found that developing polycythemia while on TRT is an independent risk factor for MACE and VTE in the first year of therapy 6.