Rodriguez-Wallberg Kenny A, Pfau Daniel R
Reproduction. 2025 Jan 9;169(2). doi: 10.1530/REP-24-0046. Print 2025 Feb 1.
Transgender, non-binary and gender-diverse patients utilizing feminizing gender-affirming hormone therapy (GAHT) may experience reduced fertility, which is currently addressed through fertility preservation and treatment cessation. Experimental research with animal models may identify mechanisms involved in testicular function impairment, their severity and duration, and may help to inform patients about reproductive health decisions.
Feminizing GAHT may include combined estrogen, progesterone and/or antiandrogens (collectively referred to as E-GAHT) aiming to achieve individualized embodiment goals. This kind of treatment is highly desired, but it is expected to negatively impact the reproductive ability of transgender, non-binary and/or gender-diverse (TNG) individuals having testes, mainly by disrupting the biological pathways involved in spermatogenesis. There is little research on the impact of E-GAHT on the testis or on the potential recovery of spermatogenesis by stopping GAHT. Studies using animal models receiving GAHT are a novel promising method to help identify the reproductive pathways affected by GAHT and the degree of those effects. A literature search was performed to identify both clinical and experimental studies using rodent models applicable to the reproductive needs of E-GAHT users. We found large variability in clinical populations that has not been fully replicated in translational research. Furthermore, animal GAHT models have yet to be capitalized to examine fertility preservation. Some clinical studies indicated that sperm quality may be reduced in E-GAHT patients before initiating E-GAHT, which cannot be studied using GAHT-treated animals. As many TNG people of reproductive age may have the wish to create a future family, it is important to increase the knowledge that will inform and improve E-GAHT patients' fertility preservation outcomes and reproductive health.
使用女性化性别肯定激素疗法（GAHT）的跨性别、非二元性别和性别多样化患者可能会出现生育能力下降的情况，目前通过生育力保存和停止治疗来解决这一问题。对动物模型进行的实验研究可能会确定睾丸功能受损所涉及的机制、其严重程度和持续时间，并有助于为患者提供有关生殖健康决策的信息。
女性化GAHT可能包括联合使用雌激素、孕激素和/或抗雄激素（统称为E-GAHT），旨在实现个体化的身体塑造目标。这种治疗方法备受期待，但预计会对有睾丸的跨性别、非二元性别和/或性别多样化（TNG）个体的生殖能力产生负面影响，主要是通过扰乱参与精子发生的生物学途径。关于E-GAHT对睾丸的影响或停止GAHT后精子发生的潜在恢复情况，研究较少。使用接受GAHT的动物模型进行研究是一种新的有前景的方法，有助于确定受GAHT影响的生殖途径及其影响程度。进行了文献检索，以确定适用于E-GAHT使用者生殖需求的啮齿动物模型的临床和实验研究。我们发现临床人群存在很大差异，而转化研究尚未完全复制这种差异。此外，动物GAHT模型尚未被用于研究生育力保存。一些临床研究表明，在开始E-GAHT之前，E-GAHT患者的精子质量可能会下降，而这无法使用接受GAHT治疗的动物进行研究。由于许多育龄TNG人群可能希望组建未来的家庭，因此增加相关知识以告知并改善E-GAHT患者的生育力保存结果和生殖健康非常重要。
