Abstract：
The effects of gender affirming hormone therapy (GAHT) on bone microarchitecture and fracture risk in adult transgender women is unclear. To investigate the concept that skeletal integrity and strength in trans women may be improved by treatment with a higher dose of GAHT than commonly prescribed, we treated adult male mice with a sustained, high dose of estradiol. Adult male mice at 16 weeks of age were administered ~1.3 mg estradiol by silastic implant, implanted intraperitoneally, for 12 weeks. Controls included vehicle treated intact females and males. High-dose estradiol treatment in males stimulated the endocortical deposition of bone at the femoral mid-diaphysis, increasing cortical thickness and bone area. This led to higher stiffness, maximum force, and the work required to fracture the bone compared to male controls, while post-yield displacement was unaffected. Assessment of the material properties of the bone showed an increase in both elastic modulus and ultimate stress in the estradiol treated males. Treatment of male mice with high dose estradiol was also anabolic for trabecular bone, markedly increasing trabecular bone volume, number and thickness in the distal metaphysis which was accompanied by an increase in the histomorphometric markers of bone remodelling, mineralizing surface/bone surface, bone formation rate and osteoclast number. In conclusion, a high dose of estradiol is anabolic for cortical and trabecular bone in a male to female transgender mouse model, increasing both stiffness and strength. These findings suggest that increasing the current dose of GAHT administered to trans women, while considering other potential adverse effects, may be beneficial to preserving their bone microstructure and strength.
摘要：
性别确认激素疗法（GAHT）对成年变性女性的骨微结构和骨折风险的影响尚不清楚。为了研究跨性别女性的骨骼完整性和力量可以通过使用比通常规定的更高剂量的GAHT治疗来改善的概念，我们用持续的雄性小鼠治疗，高剂量的雌二醇。16周龄的成年雄性小鼠通过硅橡胶植入给药〜1.3mg雌二醇，腹膜内植入,12周。对照包括载体处理的完整女性和男性。男性的高剂量雌二醇治疗刺激了股骨中骨干骨的皮质内沉积，增加皮质厚度和骨面积。这导致了更高的刚度，最大力,与男性对照组相比，骨折所需的工作，而产量后的位移不受影响。对骨材料特性的评估显示，雌二醇处理的雄性的弹性模量和极限应力均增加。用高剂量雌二醇治疗雄性小鼠也是小梁骨的合成代谢，骨小梁体积明显增加，远端干phy端的数量和厚度，伴随着骨骼重塑的组织形态指标的增加，矿化表面/骨表面，骨形成率和破骨细胞数量。总之,高剂量的雌二醇是合成代谢的皮质和骨小梁在雄性到雌性变性小鼠模型，增加刚度和强度。这些发现表明，增加目前对跨性别女性的GAHT剂量，同时考虑到其他潜在的不利影响，可能有利于保持其骨的微结构和强度。
