The influence of gender-affirming hormone therapy on serum concentrations of hormone-binding proteins

Corticosteroid-binding globulin (CBG), thyroid-binding globulin (TBG), sex hormone-binding globulin (SHBG), and insulin-like growth factor-binding protein 3 (IGF-BP3) regulate the bioavailability and transport of hormones, affecting hormone concentration measurements and therapy plans. This study investigates to what extent gender-affirming hormone therapy (GAHT) impacts serum concentrations of these binding proteins.

This prospective study included 41 transfeminine persons starting oral or transdermal 17β-estradiol in combination with cyproterone acetate (CPA) or gonadotropin-releasing hormone analogs (GnRHa) and 38 transmasculine persons starting testosterone gel or injections. Serum concentrations of CBG (mg/L), TBG (nmol/L), SHBG (nmol/L), and IGF-BP3 (mg/L) were measured at baseline and after 3 and 12 months. Changes were analyzed using mixed models and reported as percentage change.

In oral estradiol and CPA users, CBG increased by 29% (95% CI, 16, 44%), TBG by 24% (95% CI, 16, 32%), SHBG by 81% (95% CI, 61, 105%) and in oral estradiol and GnRHa users by 47% (95% CI, 7, 101%), 48% (95% CI, 9, 101%), and 242% (95% CI, 104, 474%), respectively. The IGF-BP3 remained unchanged. In transdermal estradiol users, only SHBG changed (+63% [95% CI, 3, 157%]), when combined with GnRHa. In transmasculine participants, CBG, TBG, SHBG, and IGF-BP3 decreased by 13% (95% CI, -21, -4%), 11% (95% CI, -15, -6%), 43% (95% CI, -48, -36%), and 10% (95% CI, -18, -2%) respectively, with no difference in gel vs injections.

The GAHT led to an increase of CBG, TBG, and SHBG in estradiol users, more specifically oral estradiol, and to a decrease of SHBG, CBG, TBG, and IGF-BP3 in testosterone users. Recognizing these alterations is crucial for ensuring accurate hormone measurements and optimal patient care.