Stangl Theresa A, Wiepjes Chantal M, Heijboer Annemieke C, den Heijer Martin
Department of Endocrinology and Metabolism, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam Gastroenterology Endocrinology & Metabolism, Center of Expertise on Gender Dysphoria, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Department of Laboratory Medicine, Amsterdam UMC, Location Vrije Universiteit Amsterdam and location University of Amsterdam, Endocrine Laboratory, Amsterdam Gastroenterology Endocrinology & Metabolism, Amsterdam Reproduction & Development, De Boelelaan 1117 1081 HV Amsterdam, and Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Eur J Endocrinol. 2025 Apr 30;192(5):614-620. doi: 10.1093/ejendo/lvaf038.
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.
皮质类固醇结合球蛋白（CBG）、甲状腺结合球蛋白（TBG）、性激素结合球蛋白（SHBG）和胰岛素样生长因子结合蛋白3（IGF - BP3）调节激素的生物利用度和转运，影响激素浓度测量和治疗方案。本研究调查性别确认激素疗法（GAHT）在多大程度上影响这些结合蛋白的血清浓度。
这项前瞻性研究纳入了41名开始口服或经皮使用17β - 雌二醇联合醋酸环丙孕酮（CPA）或促性腺激素释放激素类似物（GnRHa）的跨性别女性和38名开始使用睾酮凝胶或注射剂的跨性别男性。在基线以及3个月和12个月后测量CBG（mg/L）、TBG（nmol/L）、SHBG（nmol/L）和IGF - BP3（mg/L）的血清浓度。使用混合模型分析变化情况，并以百分比变化报告。
在口服雌二醇和CPA使用者中，CBG增加了29%（95%CI，16，44%），TBG增加了24%（95%CI，16，32%），SHBG增加了81%（95%CI，61，105%）；在口服雌二醇和GnRHa使用者中，CBG增加了47%（95%CI，7，101%），TBG增加了48%（95%CI，9，101%），SHBG增加了242%（95%CI，104，474%）。IGF - BP3保持不变。在经皮雌二醇使用者中，仅在与GnRHa联合使用时SHBG发生变化（增加63%[95%CI，3，157%]）。在跨性别男性参与者中，CBG、TBG、SHBG和IGF - BP3分别下降了13%（95%CI， - 21， - 4%）、11%（95%CI， - 15， - 6%）、43%（95%CI， - 48， - 36%）和10%（95%CI， - 18， - 2%），凝胶与注射剂之间无差异。
GAHT导致雌二醇使用者，更具体地说是口服雌二醇使用者的CBG、TBG和SHBG增加，以及睾酮使用者的SHBG、CBG、TBG和IGF - BP3下降。认识到这些变化对于确保准确的激素测量和最佳的患者护理至关重要。
