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

Context: The long-term effect of gender-affirming hormone therapy (GAHT) on glucose metabolism is an area of priority in transgender health research.

Objectives: To evaluate the relation between GAHT and changes in fasting blood glucose (FG) and glycosylated hemoglobin (HbA1c) in transmasculine (TM) and transfeminine (TF) persons relative to the corresponding temporal changes in presumably cisgender persons (ie, without any evidence of gender diversity).

Design: Retrospective cohort study.

Setting: Three large integrated health systems.

Participants: A total of 2148 TF and 1679 TM persons compared with 28 036 cisgender males and 32 548 cisgender females enrolled in the same health plans.

Outcomes/measures: Temporal changes in FG and HbA1c levels examined using linear mixed models with main results expressed as ratios-of-ratios.

Results: The pre- vs post-GAHT ratios-of-ratio (95% CI) estimates adjusted for age, race/ethnicity, study site, and body mass index in the model comparing TF and cisgender males groups were 1.05 (1.01-1.09) for FG and 1.03 (0.99-1.06) for HbA1c. By contrast, the corresponding results in the models contrasting TM and cisgender cohort members were in the 0.99 to 1.00 range. The ratio-of-ratios comparing post-GAHT changes among transgender and cisgender persons were close to the null and without a discernable pattern.

Conclusion: Though the within-transgender cohort data suggest an increase in the levels of FG and HbA1c following feminizing GAHT initiation, these changes were no longer evident when compared with the corresponding changes in cisgender referents. Based on these results, clinically important effects of GAHT on routine laboratory markers of glucose metabolism appear unlikely.