Cardiometabolic Health in Transgender Males

Transgender individuals are those with a gender identity opposite the sex they were assigned at birth. Approximately 1% of the population is transgender, equating to \~60,000 transgender Wisconsinites. A transgender boy or man is someone with a 46,XX karyotype and typical female genitalia but a male gender identity and desire for more male-typical gender expression. Gender-affirming testosterone (hormonal) treatment (GAHT) is the cornerstone of masculinizing therapy for transgender men and boys, resulting in estrogen (E2) suppression and circulating testosterone (T) levels equivalent to cisgender males. Historically, GAHT was initiated after an E2-driven puberty, but the last decade has seen an explosion of referrals for GAHT in transboys, many of whom are exposed to only low E2 levels before puberty is halted with blocker therapy. Knowledge of risks incurred by GAHT rely on low-quality studies, precluding conclusive assessment of GAHT's long-term impact on cardiometabolic outcomes. Data on transboys receiving GAHT before completion of E2-driven puberty are sparser and no studies have addressed mechanisms by which GAHT may affect vascular physiology. The investigators aim to determine the cardiometabolic impact of GAHT in transboys/men and to determine if any differences identified are mechanistically dependent on the timing of GAHT relative to puberty.