The effects of gender-affirming hormone therapy on the skeletal integrity and fracture risk in transitioning adolescent trans girls are unknown. To address this knowledge gap, we developed a mouse model to simulate male-to-female transition in human adolescents in whom puberty is first arrested by using gonadotrophin-releasing hormone analogs with subsequent estradiol treatment. Puberty was suppressed by orchidectomy in male mice at 5 weeks of age. At 3 weeks post-surgery, male-to-female mice were treated with a high dose of estradiol (~0.85 mg) by intraperitoneal silastic implantation for 12 weeks. Controls included intact and orchidectomized males at 3 weeks post-surgery, vehicle-treated intact males, intact females and orchidectomized males at 12 weeks post-treatment. Compared to male controls, orchidectomized males exhibited decreased peak bone mass accrual and a decreased maximal force the bone could withstand prior to fracture. Estradiol treatment in orchidectomized male-to-female mice compared to mice in all control groups was associated with an increased cortical thickness in the mid-diaphysis, while the periosteal circumference increased to a level that was intermediate between intact male and female controls, resulting in increased maximal force and stiffness. In trabecular bone, estradiol treatment increased newly formed trabeculae arising from the growth plate as well as mineralizing surface/bone surface and bone formation rate, consistent with the anabolic action of estradiol on osteoblast proliferation. These data support the concept that skeletal integrity can be preserved and that long-term fractures may be prevented in trans girls treated with GnRHa and a sufficiently high dose of GAHT. Further study is needed to identify an optimal dose of estradiol that protects the bone without adverse side effects.

性别肯定激素治疗对变性青春期跨性别女孩骨骼完整性和骨折风险的影响尚不清楚。为了解决这一知识差距，我们开发了一种小鼠模型来模拟人类青少年从男性到女性的转变，其中首先通过使用促性腺激素释放激素类似物和随后的雌二醇治疗来阻止青春期。 5周龄雄性小鼠的睾丸切除术抑制了青春期。术后 3 周，通过腹腔硅橡胶植入法对雄性小鼠和雌性小鼠进行高剂量雌二醇（~0.85 mg）治疗，持续 12 周。对照组包括手术后 3 周的完整雄性和睾丸切除的雄性、治疗后 12 周时接受媒介物处理的完整雄性、完整雌性和睾丸切除的雄性。与男性对照组相比，睾丸切除的男性表现出峰值骨量减少和骨折前骨骼可承受的最大力减少。与所有对照组的小鼠相比，睾丸切除的雄性至雌性小鼠的雌二醇治疗与中骨干皮质厚度的增加有关，而骨膜周长增加至完整雄性和雌性对照组之间的中间水平，导致增加最大力和刚度。在小梁骨中，雌二醇治疗增加了生长板新形成的小梁以及矿化表面/骨表面和骨形成率，这与雌二醇对成骨细胞增殖的合成代谢作用一致。这些数据支持这样的概念：接受 GnRHa 和足够高剂量的 GAHT 治疗的跨性别女孩可以保留骨骼完整性，并且可以预防长期骨折。 需要进一步的研究来确定雌二醇的最佳剂量，以保护骨骼而不产生不良副作用。