Does parenteral testosterone have any effect on the complete blood count (CBC)?

From the Guidelines

Parenteral testosterone can significantly affect the complete blood count (CBC), particularly by increasing red blood cell production, which may lead to elevated hemoglobin, hematocrit, and red blood cell count, as evidenced by studies such as 1 and 1. This effect is dose-dependent and more pronounced with injectable forms compared to topical preparations. The increase in hematocrit typically ranges from 3-5% but can be higher in some individuals. Testosterone stimulates erythropoietin production in the kidneys and directly affects bone marrow stem cells, leading to this increase in red blood cell production. Some key points to consider include:

• Clinically significant polycythemia (hematocrit >54%) may develop in approximately 5-10% of patients on testosterone therapy, particularly with supraphysiologic doses, as noted in 1.
• This risk necessitates regular CBC monitoring during treatment, typically every 3-6 months initially and then annually once stable.
• If polycythemia develops, management options include dose reduction, changing to a different testosterone formulation, therapeutic phlebotomy, or discontinuation of therapy.
• Patients with baseline elevated hematocrit should be evaluated for underlying causes before starting testosterone therapy, highlighting the importance of careful patient selection and monitoring, as discussed in 1. Given the potential for significant effects on the CBC, particularly with parenteral testosterone, it is crucial to monitor patients closely for signs of erythrocytosis and to manage it appropriately to prevent complications, as emphasized by the findings in 1.

From the FDA Drug Label

Androgens have been reported to stimulate production of red blood cells by enhancing production of erythropoietic stimulation factor The parenteral testosterone has an effect on the CBC, specifically it stimulates the production of red blood cells by enhancing the production of erythropoietic stimulation factor 2.

• This effect is due to the anabolic properties of androgens, which can influence the production of red blood cells.
• The exact mechanism of this effect is not fully described in the label, but it is related to the enhancement of erythropoietic stimulation factor.

From the Research

Effect of Parenteral Testosterone on CBC

• Parenteral testosterone therapy has been shown to increase hematocrit and red blood cell volume in hypogonadal men 3.
• This increase in hematocrit can lead to secondary erythrocytosis, a common adverse event associated with testosterone therapy (TT) 4.
• Studies have found that men undergoing testosterone replacement therapy (TRT) have a 3-15% greater risk for developing erythrocytosis (defined as Hct > 0.52) when compared with control 5.
• The mechanisms behind TRT-induced erythrocytosis involve iron bioavailability, erythropoietin production, and bone marrow stimulation 5.
• All TRT formulations cause increases in hemoglobin (Hb) and hematocrit (Hct), but injectables tend to produce the greatest effect 5, 6.
• The association between TRT-induced erythrocytosis and subsequent risk for venous thromboembolism (VTE) remains inconclusive 5, 7.
• Regular laboratory monitoring and discontinuing TRT or reducing the dose if the hematocrit exceeds 54% is recommended to minimize the risk of adverse vascular events 7.

Comparison of Testosterone Formulations

• A systematic review and Bayesian network meta-analysis of randomized trials found that all types of testosterone therapies result in statistically significant increases in mean hematocrit when compared with placebo 6.
• Intramuscular testosterone enanthate/cypionate were associated with a significantly higher increase in mean hematocrit compared to patch, but no differences in hematocrit between other formulations were detected 6.
• The clinical concern of the increase in hematocrit remains questionable, warranting future studies 6.