Impact of Testosterone on Endothelial Function Varies by GnRH Agonist Treatment

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Abstract Context Transgender adults taking testosterone have impaired endothelial function, a triggering mechanism for cardiovascular disease. The impact of testosterone with and without gonadotropin-releasing hormone agonists (GnRHa) on endothelial function in transgender adolescents is unknown. Objective To evaluate the effects of 12 months of testosterone therapy on endothelial function among transgender adolescents and whether the effects differ based on exposure to GnRHa. Design Longitudinal, observational study with assessments prior to and after 1 and 12 months of testosterone therapy. Setting Academic regional referral center. Participants Nineteen adolescents with a female sex (8 receiving GnRHa, 11 not receiving GnRHa). Interventions Clinically prescribed testosterone. Main Outcome Measures Endothelial function assessed by brachial artery flow mediated dilation (FMD) at baseline and after 1 and 12 months testosterone therapy. Differences between groups were assessed at baseline by t-test and over time with a linear regression model with a time*group interaction. Results FMD was lower in GnRHa + compared to GnRHa− individuals at baseline (7.9 ± 2.5% vs 10.9 ± 2.9%, P = .029) and after 1 month (P = .042) of testosterone therapy. After 12 months of testosterone, FMD was similar between groups: 9.9 ± 4.2% for GnRHa + and 9.8 ± 2.8% for GnRHa− (P = .965). There was a significant interaction in the linear regression model for FMD (P = .030) with an increase in FMD for GnRHa + individuals and a decrease in FMD for GnRHa− individuals after 12 months of testosterone. Conclusion Prior to testosterone therapy, GnRHa + individuals had lower endothelial function compared to GnRHa− individuals. The effects of testosterone on endothelial function were modulated by GnRHa status.

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