Association Between Gender-affirming Hormone Therapy and Measures of Glucose Metabolism: A Longitudinal Study.

Feminizing GAHT was associated with a small but statistically significant increase in fasting blood glucose relative to cisgender males after adjusting for covariates.

• The pre- vs post-GAHT ratio-of-ratio (95% CI) for fasting glucose comparing transfeminine and cisgender males groups was 1.05 (1.01-1.09)
• The corresponding ratio-of-ratio for HbA1c comparing transfeminine and cisgender males was 1.03 (0.99-1.06), which was not statistically significant
• Models were adjusted for age, race/ethnicity, study site, and body mass index
• The study included 2148 transfeminine persons compared with 28,036 cisgender males

Masculinizing GAHT showed no meaningful association with changes in fasting blood glucose or HbA1c relative to cisgender females.

• Ratio-of-ratio estimates for models contrasting transmasculine and cisgender cohort members were in the 0.99 to 1.00 range for both FG and HbA1c
• The study included 1,679 transmasculine persons compared with 32,548 cisgender females
• Results were adjusted for age, race/ethnicity, study site, and body mass index

Post-GAHT changes in glucose metabolism markers among transgender persons were close to null when compared with corresponding temporal changes in cisgender referents.

• Ratio-of-ratios comparing post-GAHT changes among transgender and cisgender persons were 'close to the null and without a discernable pattern'
• Within-transgender cohort data suggested an increase in FG and HbA1c following feminizing GAHT initiation, but these changes were no longer evident when compared with cisgender referents
• This pattern suggests secular trends or other time-varying confounders may explain within-group changes observed in transgender cohorts

The study used a retrospective cohort design at three large integrated health systems with a substantial sample of transgender and cisgender participants.

• Total sample included 2,148 transfeminine persons, 1,679 transmasculine persons, 28,036 cisgender males, and 32,548 cisgender females
• Data were drawn from three large integrated health systems
• Cisgender referents were defined as persons without any evidence of gender diversity enrolled in the same health plans
• Temporal changes in FG and HbA1c were examined using linear mixed models with results expressed as ratios-of-ratios

The use of cisgender comparison groups was critical to contextualizing within-transgender cohort changes in glucose metabolism, as secular temporal trends appeared to account for observed increases.

• Without cisgender comparators, the within-transgender data suggested increases in FG and HbA1c following feminizing GAHT
• These increases were no longer evident after comparison with temporal changes in cisgender males
• The authors concluded that 'clinically important effects of GAHT on routine laboratory markers of glucose metabolism appear unlikely'
• This finding highlights the importance of including cisgender comparison groups in transgender health research to distinguish GAHT effects from background temporal trends