Erythrocytosis in a Large Cohort of Trans Men Using Testosterone: A Long Term Follow up Study on Prevalence, Determinants, and the Effect of Years of Exposure

Background: Erythrocytosis is a known side effect of testosterone therapy in hypogonadal men and can increase the risk of thromboembolic events. Erythrocytosis is also seen in trans men (birth-assigned female, male gender identity) receiving testosterone therapy. Currently there are no clinical guidelines for the management of this problem in trans men. Specific aims: 1. To study the prevalence and determinants in the development of erythrocytosis in trans men using testosterone. 2. To study the association between duration of testosterone treatment and hematocrit levels. Methods: A 20 year follow-up study in adult trans men who started testosterone, and had monitoring of hematocrit levels at our center (n=1073). Results: Erythrocytosis (defined as hematocrit levels of >0.50 l/l twice) occurred in 11% of trans men. Multilevel analyses showed former or current smoking (OR 2.2, 95%CI 1.6-3.3), testosterone administration as long-acting intramuscular injection (OR 2.9, 95% CI 1.7-5.0), a higher age at initiation of hormone therapy (up to OR 5.9, 95% CI 2.8-12.3) for people above 40 compared to <18), higher BMI (>30 g/m2 compared to 18.5-25 kg/m2) (OR 3.7, 95% CI 2.2-6.2) and a medical history for chronic pulmonary diseases, sleep apnea or polycythemia vera (OR 2.5, 95% CI 1.4-4.4) as determinants that increased the risk of high hematocrit levels. In the first year of testosterone therapy hematocrit levels increased most: from 0.39 l/l at baseline to 0.45 l/l after 1 year. Although there was only a slight continuation of this increase in the following 20 years (0.45 at 1 year and 0.46 at 20 years), the probability of developing erythrocytosis still increased (10% after 1 year, 38% after 20 years). Conclusion: Erythrocytosis frequently occurs in trans men using testosterone. The biggest increase in hematocrit was seen in the first year, but also after the first years there is a substantial number of people that present with hematocrit >0.50. Because smoking, obesity and use of injection as dosage form are associated with a higher risk for erythrocytosis, a reasonable first step in the care for transmen with erythrocytosis while on testosterone is to advise them to quit smoking and to switch to a transdermal administration type and if BMI is high, to lose weight.