Gender-affirming hormone therapy led to increases in CBG, TBG, and SHBG in estradiol users (more specifically oral estradiol) and decreases in SHBG, CBG, TBG, and IGF-BP3 in testosterone users.
Key Findings
Results
Oral estradiol combined with cyproterone acetate (CPA) significantly increased CBG, TBG, and SHBG concentrations.
CBG increased by 29% (95% CI, 16, 44%)
TBG increased by 24% (95% CI, 16, 32%)
SHBG increased by 81% (95% CI, 61, 105%)
IGF-BP3 remained unchanged in this group
Measurements were taken at baseline and after 3 and 12 months using mixed models
Results
Oral estradiol combined with GnRH analogs produced larger increases in CBG, TBG, and SHBG compared to oral estradiol with CPA.
CBG increased by 47% (95% CI, 7, 101%)
TBG increased by 48% (95% CI, 9, 101%)
SHBG increased by 242% (95% CI, 104, 474%)
The confidence intervals for GnRHa combinations were notably wider than for CPA combinations, suggesting greater variability
Results
Transdermal estradiol had limited effects on binding proteins, with only SHBG changing and only when combined with GnRH analogs.
SHBG increased by 63% (95% CI, 3, 157%) in transdermal estradiol plus GnRHa users
CBG and TBG did not show significant changes with transdermal estradiol
This contrasts with the broader effects seen with oral estradiol administration
Results
Testosterone therapy in transmasculine persons decreased all four measured binding proteins.
CBG decreased by 13% (95% CI, -21, -4%)
TBG decreased by 11% (95% CI, -15, -6%)
SHBG decreased by 43% (95% CI, -48, -36%)
IGF-BP3 decreased by 10% (95% CI, -18, -2%)
No difference was found between testosterone gel and injections
38 transmasculine persons were included in this arm
Methods
The study prospectively followed transfeminine and transmasculine participants starting gender-affirming hormone therapy over 12 months.
41 transfeminine persons starting oral or transdermal 17β-estradiol in combination with CPA or GnRHa were included
38 transmasculine persons starting testosterone gel or injections were included
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
Stangl T, Wiepjes C, Heijboer A, den Heijer M. (2025). The influence of gender-affirming hormone therapy on serum concentrations of hormone-binding proteins.. European journal of endocrinology. https://doi.org/10.1093/ejendo/lvaf038