SUN-127 Karyotype and Hormonal Exposure as Predictors of Erythrocytosis Risk in Testosterone Treated Individuals

Abstract Disclosure: J.P. Batatinha: None. M.C. Mesia: None. H.C. Cecotti: None. E.F. Costa: None. S. Domenice: None. Testosterone therapy is vital for the health and well-being of hypogonadal cisgender men and 46,XX individuals with a male gender identity. While it restores eugonadism and improves quality of life, it also carries risks, including erythrocytosis, which can increase cardiovascular and thrombotic risks. Most studies have focused on hypogonadal cisgender men, leaving limited data on the prevalence and risk factors of erythrocytosis in transgender men (TM) and individuals with differences in sex development (DSD) who are undergoing testosterone therapy. Objective- To evaluate the prevalence of erythrocytosis in TM and individuals with 46,XX and 46,XY DSD undergoing testosterone therapy (TTh), and to assess how karyotype, the age at which testosterone therapy is initiated, and prior estrogen exposure during puberty may influence the risk of erythrocytosis. Methods- This cohort study included 124 individuals: 75 with 46,XX karyotypes (64 TM, 6 ovariotesticular DSD, 5 congenital adrenal hyperplasia), 40 with 46,XY karyotypes (DSD and hypogonadism), and 9 DSD with sex chromosomal abnormalities. All received IM testosterone cypionate or undecylenate for an average duration of 15.6 yrs (range of 13.6-17.7). Erythrocytosis was defined as hematocrit (Ht) levels >50% and confirmed through two measurements. Participants were grouped as erythrocytosis (n=66; Ht ≥50%) or non-erythrocytosis (n=68; Ht <50%). Clinical and laboratory data were retrospectively analyzed. Results- Erythrocytosis prevalence was 45.2%. It was more frequent in individuals with 46,XX karyotypes (53.95%) than 46,XY karyotypes (32.5%) (p = 0.028). Erythrocytosis was also associated with spontaneous endogenous female puberty (p = 0.009), particularly TM. The erythrocytosis group had higher mean pre-TTh Ht levels (46.3% vs. 41.7%, p < 0.001) and started testosterone therapy at an older age (28.3 ± 10.8 yrs vs. 24.2 ± 11.1 yrs, p = 0.047), regardless of karyotype. Conclusion- This study reveals a high prevalence of erythrocytosis among Brazilian individuals on testosterone therapy, particularly within the 46,XX population, mainly TM, underscoring a potential role for previous estrogen exposure. Key factors such as baseline hematocrit levels and age at treatment onset, emphasize the need for careful monitoring and awareness of erythrocytosis in this population. Clinicians should take individual patient characteristics into account to optimize management and ensure safe, effective treatment outcomes. Presentation: Sunday, July 13, 2025