What is the effect of testosterone on blood?

From the Guidelines

Testosterone therapy can increase the risk of polycythemia, a condition characterized by excessive red blood cell production, which can lead to increased blood viscosity and potentially raise the risk of blood clots, stroke, or heart attack. This effect occurs because testosterone stimulates erythropoiesis (red blood cell formation) in the bone marrow by enhancing erythropoietin production in the kidneys 1. While this can be beneficial for individuals with anemia, it is crucial to monitor hemoglobin and hematocrit levels regularly in patients on testosterone therapy, with normal target hematocrit levels below 54% 1.

Some key points to consider when evaluating the effect of testosterone on blood include:

• Testosterone therapy may result in improvements in anemia, among other benefits 1
• Prior to commencing testosterone therapy, baseline measurement of hemoglobin/hematocrit is necessary, and if the hematocrit exceeds 50%, clinicians should consider withholding testosterone therapy until the etiology is formally investigated 1
• Injectable testosterone is associated with the greatest treatment-induced increases in hemoglobin/hematocrit 1
• The risk of polycythemia and other adverse effects, such as increased blood pressure, gynecomastia, and fluid retention, should be carefully considered when prescribing testosterone therapy 1

In terms of management, if hematocrit levels become too high, doctors may recommend temporarily stopping testosterone treatment, reducing the dose, or performing therapeutic phlebotomy (blood removal) to maintain safe blood parameters. It is essential to weigh the benefits of testosterone therapy against the potential risks and to closely monitor patients to minimize adverse effects 1.

From the FDA Drug Label

Hemoglobin and hematocrit levels (to detect polycythemia) should be checked periodically in patients receiving long-term androgen administration. Serum cholesterol may increase during androgen therapy. Androgens may increase sensitivity to oral anticoagulants

The effect of testosterone on blood is that it may lead to:

• Polycythemia, which can be detected by checking hemoglobin and hematocrit levels
• Increased serum cholesterol levels
• Increased sensitivity to oral anticoagulants, which may require a reduction in anticoagulant dosage 2

From the Research

Effects of Testosterone on Blood

• Testosterone administration has been shown to increase hemoglobin levels and has been used to treat anemia of chronic disease 3.
• The mechanisms by which testosterone increases hemoglobin involve the inhibition of hepcidin transcription, which leads to increased iron incorporation into red blood cells 3.
• Testosterone therapy has been associated with erythrocytosis, which is the most frequent adverse event in hypogonadal men, especially older men 3, 4.
• The increase in hemoglobin and hematocrit with testosterone administration is associated with significantly increased erythropoietin levels and decreased ferritin and hepcidin levels 5.
• Testosterone-induced increase in hemoglobin and hematocrit is also associated with stimulation of erythropoiesis and increased iron utilization for erythropoiesis 5.
• The risk of erythrocytosis with testosterone therapy is dose-dependent, with higher doses leading to greater increases in hemoglobin and hematocrit 6.
• Age-related differences in response to testosterone therapy may be mediated by factors other than erythropoietin and soluble transferrin receptor levels 6.
• Severe erythrocytosis (hematocrit >54%) is a rare outcome of gender-affirming testosterone therapy, and clinical recommendations should reconsider the need for routine frequent erythrocytosis screening within the first year of testosterone therapy 7.

Key Findings

• Testosterone administration increases hemoglobin levels and inhibits hepcidin transcription 3.
• Testosterone therapy is associated with erythrocytosis, especially in older men 3, 4.
• The increase in hemoglobin and hematocrit with testosterone administration is associated with increased erythropoietin levels and decreased ferritin and hepcidin levels 5.
• Testosterone-induced increase in hemoglobin and hematocrit is dose-dependent and more pronounced in older men 6.