Polycythemia secondary to testosterone therapy in transgender individuals is a common adverse reaction of gender-affirming treatment. Testosterone therapy, a cornerstone of masculinizing hormone therapy for transgender men and transmasculine non-binary individuals, has been associated with secondary polycythemia, a condition characterized by an elevated hematocrit and increased blood viscosity.

The risk of developing polycythemia secondary to testosterone therapy varies among individuals and can be influenced by the dose and route of administration. Intramuscular testosterone has been associated with higher peaks in testosterone levels and a greater risk of polycythemia compared to transdermal testosterone.1 Because testosterone-associated and other forms of secondary polycythemia have not been widely studied, the management of secondary polycythemia is similar to that of polycythemia vera (PV) in practice.2 As PV is associated with an increased risk of thromboembolic events including stroke and deep vein thrombosis, the mainstays of PV treatment include therapeutic phlebotomy, low dose aspirin and management of other cardiovascular risk factors.

Because testosterone therapy is an essential component of gender-affirming treatment for many transgender individuals,3 management of polycythemia and other complications of testosterone therapy in transgender individuals on testosterone therapy is crucial. Potential strategies to mitigate polycythemia include decreasing the dose of intramuscular testosterone, switching to topical testosterone, or therapeutic phlebotomy. Because there are often multiple barriers to administering therapeutic phlebotomy, blood donation is often recommended as a method to mitigate testosterone-related polycythemia, though this strategy has not been extensively studied.

In conclusion, while testosterone therapy offers life-changing benefits for transgender individuals, it carries the risk of secondary polycythemia. The incidence of polycythemia varies with the testosterone dose and administration route, with intramuscular injections posing a higher risk compared to transdermal methods. However, the unique challenges faced by the transgender community necessitate more accessible and transgender-specific research on interventions to mitigate the risks of secondary polycythemia.