Background A low concentration of Sex Hormone Binding Globulin (SHBG) is associated with type 2 diabetes, metabolic syndrome, and fatty liver. Previous studies in cis persons demonstrated that SHBG concentrations are influenced by sex hormones. In this study we aim to investigate if gender-affirming hormone therapy influences SHBG concentrations in transgender persons.

Methods This study is part of the European Network for the Investigation of Gender Incongruence, a multicenter cohort study. Trans women received oral or transdermal estradiol in combination with anti-androgen treatment (cyproterone acetate or GnRH analogues). Trans men received transdermal or intramuscular testosterone. Data was collected at baseline, after 3 and 12 months after start of hormone treatment. Changes over time were analyzed using linear mixed models and were stratified for type of hormone administration.

Results 82 trans women and 88 trans men were included. Trans women had mean (SD) baseline SHBG levels of 35 (16) nmol/L and trans men 50 (26) nmol/L (female reference interval 18-114 nmol/L; male reference interval 13-71 nmol/L). SHBG concentrations in trans women using transdermal estradiol increased after 12 months by 8 (95%CI 5, 21) nmol/L. In trans women using oral estradiol this change was larger, with an increase after 12 months of 34 (95%CI 24, 44) nmol/L. In cyproterone acetate users an increase of SHBG after 12 months of 13 (95%CI 6, 20) was found, whereas in users of GnRH-analogues the SHBG increased with 67 (95%CI 52, 81) nmol/L after 12 months. In trans men SHBG concentrations decreased in transdermal and intramuscular testosterone users with -20 (95%CI -25, -16) nmol/L after 12 months.

Conclusion Trans women showed an increase in SHBG concentrations after start of estradiol, which was larger in participants using oral estradiol and in GnRH-analogue users. Trans men showed a decrease in SHBG concentrations. Future research should focus on the influence of SHBG concentrations on type 2 diabetes and other metabolic conditions in transgender persons using hormone therapy.