From the Guidelines
Testosterone is directly related to the development of polycythemia, as higher testosterone levels stimulate erythropoiesis, leading to increased hemoglobin and hematocrit levels 1.
Key Findings
- Testosterone-replacement therapy can increase hemoglobin levels by 15 to 20 percent, similar to the natural increase seen in boys at puberty 1.
- The risk of erythrocytosis is greater with injectable testosterone compared to topical preparations, with incidence rates ranging from 2.8 to 17.9 percent depending on the dosage and formulation 2, 3.
- Monitoring of hematocrit or hemoglobin levels is essential in men receiving testosterone-replacement therapy to prevent erythrocytosis and potential thromboembolic events 2, 4.
- A hematocrit level above 54% warrants intervention, such as dose reduction or temporary discontinuation of testosterone therapy 4.
Clinical Implications
- Patients should be informed about the potential risk of polycythemia with testosterone therapy and undergo baseline measurement of hemoglobin/hematocrit before starting treatment 4.
- Clinicians should consider withholding testosterone therapy if the hematocrit level exceeds 50% and investigate the underlying cause before initiating treatment 4.
- Management of polycythemia secondary to testosterone therapy should take into account the balance between the physiological benefit of increased hematocrit and the potential impairment of oxygen delivery to tissues due to increased whole blood viscosity 5.
From the FDA Drug Label
Hematologic: Suppression of clotting factors II, V, VII, and X, bleeding in patients on concomitant anticoagulant therapy, and polycythemia. Laboratory tests: Hemoglobin and hematocrit levels (to detect polycythemia) should be checked periodically in patients receiving long-term androgen administration.
The relationship between testosterone and polycythemia is that testosterone may cause polycythemia, a condition characterized by an increased concentration of red blood cells in the blood. This is indicated by the need to periodically check hemoglobin and hematocrit levels in patients receiving long-term androgen administration to detect polycythemia 6. Additionally, polycythemia is listed as a potential adverse reaction to testosterone therapy 7.
From the Research
Relationship Between Testosterone and Polycythemia
The relationship between testosterone and polycythemia is supported by several studies:
- A study published in the European journal of endocrinology 8 found a positive association between trough serum testosterone and the development of polycythemia in hypogonadal men treated with subcutaneous testosterone pellets.
- Another study published in the International journal of impotence research 9 discussed the pathophysiology behind testosterone therapy and secondary erythrocytosis, highlighting the need for further research on the topic.
- A review published in Sexual medicine reviews 10 examined the literature on testosterone-induced erythrocytosis and polycythemia, discussing possible mechanisms and the significance of formulation.
Risk Factors and Associations
Several risk factors and associations have been identified:
- Higher trough serum testosterone concentrations were found to predict the development of polycythemia in men receiving long-acting depot testosterone treatment 8.
- Obstructive sleep apnea (OSA) was found to be associated with polycythemia in hypogonadal men on testosterone replacement therapy 11.
- Testosterone use was found to be a primary risk factor for polycythemia in HIV-infected patients 12.
- Short-acting injectable testosterone formulations were found to have a higher associated incidence of erythrocytosis compared to other formulations 10.
Mechanisms and Pathophysiology
The mechanisms and pathophysiology of testosterone-induced erythrocytosis and polycythemia are not fully understood:
- Possible mechanisms include the role of hepcidin, iron sequestration and turnover, erythropoietin production, bone marrow stimulation, and genetic factors 10.
- A direct relationship between testosterone and erythropoietin was observed in one study 8.
- The relationship between testosterone therapy, secondary erythrocytosis, and major adverse cardiovascular events (MACE) is still being researched 9.