Lipoprotein subtypes after testosterone therapy in transmasculine adolescents.

Transmasculine adolescents on testosterone therapy had lipoprotein profiles similar to cisgender males and more atherogenic than cisgender females.

• Cross-sectional cohort study with transmasculine adolescents (n=17), cisgender males (n=33), and cisgender females (n=32)
• Transmasculine adolescents had higher concentrations of small LDL particles compared to cisgender females (435 ± 222 nmol/L vs. 244 ± 163 nmol/L, p=0.008)
• Transmasculine adolescents had lower concentrations of large HDL particles compared to cisgender females (1.5 ± 1.3 µmol/L vs. 2.7 ± 1.2 µmol/L, p=0.003)
• Lipoprotein subtype profiles were examined using particle subclass measurements rather than standard lipid panels

Sex hormone differences in lipoprotein-particle subclasses between men and women begin in puberty and narrow after menopause, suggesting a role for sex steroids.

• This observation from the literature motivated the study of testosterone's role in shaping lipoprotein profiles
• The narrowing of lipoprotein differences after menopause implicates endogenous sex steroids as key modulators
• The study used testosterone-treated transmasculine adolescents as a model to isolate the effect of testosterone on lipoprotein subtypes

Testosterone therapy in transmasculine adolescents was associated with a shift toward a more atherogenic lipoprotein subtype profile.

• The atherogenic profile was characterized by higher small LDL particle concentrations and lower large HDL particle concentrations
• Small LDL particles and reduced large HDL particles are established surrogate markers for increased cardiovascular disease risk
• The lipoprotein profile of transmasculine adolescents on testosterone was more similar to cisgender males than to cisgender females
• These findings suggest testosterone, rather than chromosomal sex, drives the male-pattern lipoprotein profile in adolescents

Testosterone appears to be a major contributor to sex-based differences in lipoprotein profiles, which serve as a surrogate for cardiovascular disease risk.

• The convergence of transmasculine and cisgender male lipoprotein profiles implicates testosterone as a key driver rather than genetic sex
• Lipoprotein subtype profiles are described as a surrogate for cardiovascular disease risk
• Findings have implications for understanding cardiovascular risk in transgender individuals undergoing gender-affirming hormone therapy