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

Abstract

Context Erythrocytosis is a known side effect of testosterone therapy that can increase the risk of thromboembolic events. Objectives To study the prevalence and determinants in the development of erythrocytosis in trans men using testosterone. Design A twenty year follow-up study in adult trans men who started testosterone therapy, and had monitoring of hematocrit at our center (n=1073). Results Erythrocytosis occurred in 11% (hematocrit>0.50 l/l), 3.7% (hematocrit>0.52 l/l) and 0.5% (hematocrit>0.54 l/l) of trans men. Tobacco use (OR 2.2, 95%CI 1.6-3.3), long-acting undecanoate injections (OR 2.9, 95%CI 1.7-5.0), age at initiation of hormone therapy (OR 5.9, 95%CI 2.8-12.3), BMI (OR 3.7, 95%CI 2.2-6.2) and pulmonary conditions associated with erythrocytosis and polycythemia vera (OR 2.5, 95%CI 1.4-4.4) were associated with hematocrit >0.50 l/l. In the first year of testosterone therapy hematocrit increased most: 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, the probability of developing erythrocytosis still increased (10% after 1 year, 38% after 10 years). Conclusion Erythrocytosis occurs in trans men using testosterone. The largest 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 l/l. A reasonable first step in the care for trans men with erythrocytosis while on testosterone is to advise them to quit smoking and to switch to a transdermal administration route and if BMI is high, to lose weight.

Gender‐affirming hormone therapy: An updated literature review with an eye on the future

“…But in trans women treated with CPA, a negative effect is seen on HDL levels [91,93,94,98]. Trans men have an increased risk of elevated hematocrit levels, but this is manageable [61,94,101,102]. The discrepancy between the effects of GAHT on cardiovascular risk factors and the available data on cardiovascular endpoints remains to be elucidated against the backdrop of changing hormonal interventions over time.…”

“…Trans men receiving shorter-acting testosterone esters had a greater increase ( 0.8%) in serum hematocrit levels compared to trans men receiving 3 monthly injections of testosterone undecanoate, which might be explained by pharmacokinetic profiles [101]. A long-term follow-up cohort study from Madsen et al [102] reported erythrocytosis in 11% (hematocrit >0.50 l/l), 3,7% (>0.52 l/l), and 0.5% (>0.54 l/l) of trans men (n = 1037, mean age at start of GAHT = 22.5) on testosterone therapy. The largest increase was seen in the first year of testosterone therapy, but the probability of developing erythrocytosis still increased in the following 20 years (10% after 1 year, 38% after 10 years) [102].…”

“…A long-term follow-up cohort study from Madsen et al [102] reported erythrocytosis in 11% (hematocrit >0.50 l/l), 3,7% (>0.52 l/l), and 0.5% (>0.54 l/l) of trans men (n = 1037, mean age at start of GAHT = 22.5) on testosterone therapy. The largest increase was seen in the first year of testosterone therapy, but the probability of developing erythrocytosis still increased in the following 20 years (10% after 1 year, 38% after 10 years) [102]. In this study, in contrast to Defreyne et al [101], longacting undecanoate showed higher risk for hematocrit levels >0.50 l/l (OR 2.9, 95% CI 1.7-5.0) compared to short-acting ester injections.…”

Effect of the spatial–temporal specific theca cell Cyp17 overexpression on the reproductive phenotype of the novel TC17 mouse

“…TC17 was also characterized by polycythemia. High levels of HCT and RBCs are typically increased in TGM, and the subsequent polycythemia is considered an adverse drug reaction lifelong hormonal therapy [ 75 , 76 ].…”

Navigating Human Immunodeficiency Virus and Primary Care Concerns Specific to the Transgender and Gender-Nonbinary Population

“…For those individuals on progesterone, use of micronized progestin rather than medroxyprogesterone acetate has been shown to decrease the risk of thromboembolism, at least among postmenopausal cisgender women [ 71 ]. Among trans men, testosterone use has also been associated with an increased risk of erythrocytosis and the development of blood clots, particularly during the first year of GAHT [ 72 ]. For all individuals on GAHT, healthcare providers should carefully explain the risk of thromboembolic events and evaluate for the presence of other CVD risk factors, particularly smoking, to provide a holistic risk-reduction approach [ 73 ].…”