Bone quality following peripubertal growth in a mouse model of transmasculine gender-affirming hormone therapy.
Bone quality following peripubertal growth in a mouse model of transmasculine gender-affirming hormone therapy.
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跨男性性别肯定激素治疗小鼠模型中青春期周围生长后的骨质量。
DOI：
10.1101/2023.12.08.570840
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Killian,MeganL
中科院分区：
文献类型：
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作者：
Henry,BrandonW;Cruz,CynthiaDela;Goulet,RobertW;Nolan,BonnieT;Locke,Conor;Padmanabhan,Vasantha;Moravek,MollyB;Shikanov,Ariella;Killian,MeganL
在青春期周围，骨骼生长和达到骨量峰值主要是由性类固醇驱动的。这在治疗越来越多出现在儿科诊所的跨性别和性别多样化的青少年时非常重要。促性腺激素释放激素（GnRH）的类似物通常在开始性别确认激素治疗（GAHT）之前开给跨性别和性别多样化的年轻人。然而，GnRH激动剂对长骨的影响与GAHT的添加是相对未知的。为了探索这一点，我们开发了一个跨男性模型，通过引入GnRHa或载体治疗雌性出生的小鼠在青春期前。在此治疗之后，三周后进行男性GAHT（睾酮，T）或对照治疗。T治疗6周后，比较4个治疗组的骨质量：对照（仅载体）、仅GnRHa、GnRHa + T和仅T。骨长度/大小、骨形状、力学性能和骨小梁形态由GAHT调节。与对照组或仅GnRHa小鼠相比，经T处理的小鼠股骨更短，小梁体积更大，小梁数量增加，小梁骨矿物质密度更高，骨表面上层结构（如第三粗隆）更宽。综上所述，长时间的GnRHa治疗和随后的GAHT治疗直接影响发育中的长骨的组成、参数和形态。这些发现为帮助指导跨性别和性别多样化青年的临床护理方法提供了见解。
During peri-puberty, bone growth and the attainment peak bone mass is driven predominantly by sex steroids. This is important when treating transgender and gender diverse youth, who have become increasingly present at pediatric clinics. Analogues of gonadotropin-releasing hormone (GnRH) are commonly prescribed to transgender and gender diverse youth prior to starting gender-affirming hormone therapy (GAHT). However, the impact of GnRH agonists on long bones with the addition of GAHT is relatively unknown. To explore this, we developed a trans-masculine model by introducing either GnRHa or vehicle treatment to female-born mice at a pre-pubertal age. This treatment was followed by male GAHT (testosterone, T) or control treatment three weeks later. Six weeks after T therapy, bone quality was compared between four treatment groups: Control (vehicle only), GnRHa-only, GnRHa + T, and T-only. Bone length/size, bone shape, mechanical properties, and trabecular morphology were modulated by GAHT. Independent of GnRHa administration, mice treated with T had shorter femurs, larger trabecular volume and increased trabecular number, higher trabecular bone mineral density, and wider superstructures on the surface of bone (e.g., third trochanters) when compared to control or GnRHa-only mice. In conclusion, prolonged treatment of GnRHa with subsequent GAHT treatment directly affect the composition, parameters, and morphology of the developing long bone. These findings provide insight to help guide clinical approaches to care for transgender and gender diverse youth.