From the Guidelines
Polycythemia in a patient with untreated sleep apnea who is also on testosterone replacement therapy is likely caused by both conditions simultaneously, with sleep apnea causing intermittent hypoxia and testosterone therapy stimulating erythropoiesis. The dual effect of these conditions creates a compounding effect, significantly elevating hemoglobin and hematocrit levels beyond what either condition would cause alone, as supported by studies such as 1 which noted a direct relation between testosterone dosage and the incidence of erythrocytosis. Key factors to consider include:
- Sleep apnea causes intermittent hypoxia during sleep, triggering increased erythropoietin production as the body attempts to compensate for low oxygen levels by producing more red blood cells.
- Testosterone therapy independently stimulates erythropoiesis in the bone marrow, further increasing red blood cell production, with research indicating that erythrocytosis occurred in a percentage of men receiving testosterone-replacement therapy, as seen in 1.
- Management should focus on treating both underlying causes: optimizing sleep apnea treatment with CPAP therapy, as recommended by guidelines such as 1 which highlights the importance of treating obstructive sleep apnoea syndrome (OSAS) to reduce cardiovascular risk, and adjusting testosterone dosing.
- Regular monitoring of complete blood counts is essential, with hematocrit levels ideally maintained below 54%, and if polycythemia becomes severe (hematocrit >54%), therapeutic phlebotomy may be necessary to reduce blood viscosity and prevent complications like thrombosis, as suggested by 1 which provides recommendations for monitoring testosterone-replacement therapy. The physiological mechanism involves hypoxia-inducible factors from sleep apnea and direct androgen stimulation of erythroid progenitor cells from testosterone, creating a perfect storm for excessive red blood cell production.
From the FDA Drug Label
5.3 Polycythemia 5.12 Sleep Apnea
The cause of polycythemia in a patient with untreated Sleep Apnea (SA) who is also on Testosterone Replacement Therapy (TRT) may be related to the testosterone replacement therapy itself, as it can increase red blood cell count, potentially leading to polycythemia. Additionally, sleep apnea can also contribute to the development of polycythemia due to chronic hypoxia, which can stimulate erythropoietin production and increase red blood cell count. However, the exact cause in this specific patient cannot be determined without further evaluation. 2
From the Research
Causes of Polycythemia
The cause of polycythemia in a patient with untreated Sleep Apnea (SA) who is also on Testosterone Replacement Therapy (TRT) can be attributed to several factors:
- Untreated severe obstructive sleep apnea can result in increased erythropoietin levels, which may contribute to the development of polycythemia 3
- Testosterone replacement therapy can also increase the risk of polycythemia, particularly in patients with hypogonadism 4
- The combination of untreated sleep apnea and testosterone replacement therapy may exacerbate polycythemia, as sleep apnea can worsen the symptoms of polycythemia and testosterone replacement therapy can increase erythropoietin levels 5, 4
Role of Sleep Apnea
Sleep apnea can contribute to the development of polycythemia through several mechanisms:
- Intermittent hypoxia and sleep fragmentation can lead to increased erythropoietin production, which can stimulate red blood cell production and contribute to polycythemia 3, 6
- Nocturnal hypoxemia can also contribute to the development of polycythemia, as it can lead to increased erythropoietin production and red blood cell production 6
Role of Testosterone Replacement Therapy
Testosterone replacement therapy can also contribute to the development of polycythemia:
- Exogenous testosterone therapy can increase hematocrit levels and contribute to the development of polycythemia 6
- Testosterone replacement therapy can also exacerbate sleep apnea symptoms, which can further contribute to the development of polycythemia 5, 7
Interaction between Sleep Apnea and Testosterone Replacement Therapy
The interaction between sleep apnea and testosterone replacement therapy can also contribute to the development of polycythemia:
- Untreated sleep apnea can worsen the symptoms of polycythemia, and testosterone replacement therapy can increase erythropoietin levels and exacerbate polycythemia 5, 4
- The combination of untreated sleep apnea and testosterone replacement therapy can increase the risk of polycythemia, particularly in patients with hypogonadism 4