Raja Nicholas S, Rubin Elizabeth S, Moravek Molly B
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97239, USA.
J Clin Med. 2024 Feb 19;13(4):1183. doi: 10.3390/jcm13041183.
Gender-affirming hormone therapy (GAHT) is an important component in the process of transitioning for many transgender and gender-diverse (TGD) individuals. Multiple medical organizations recommend fertility preservation counseling prior to initiation of GAHT; however, there remains little high-quality data regarding the impact of GAHT on fertility and reproductive function. A PubMed literature review was performed using Boolean search operators linking keywords or phrases such as "mouse", "rat", "primate", "animal model", "transgender", "gender", "estrogen", "testosterone", "fertility", and "fertility preservation". Recent research has produced a number of animal models of GAHT that utilize similar hormonal regimens and produce similar phenotypic results to those used and observed in human patients. Specific to testosterone(T)-containing GAHT, animals demonstrate loss of menstrual cyclicity with therapy, resumption of menses on cessation of therapy, suppression of gonadotropin levels, and physical changes such as clitoromegaly. Models mimicking GAHT for transmasculine individuals in the peripubertal period demonstrate that pretreatment with GnRHa therapy does not modify the effects of subsequent T administration, which were similar to those described in adult models. Both models suggest promising potential for future fertility with cessation of T. With estradiol (E)-containing GAHT, animals exhibit decreased size of testicles, epididymis, and seminal vesicles, as well as ongoing production of spermatocytes, and seminiferous tubule vacuolization. Given the ethical challenges of conducting human studies in this area, high-fidelity animal models represent a promising opportunity for investigation and could eventually transform clinical counseling about the necessity of fertility preservation. Future studies should better delineate the interactions (if any exist) between treatment attributes such as dosing and duration with the extent of reversibility of reproductive perturbations. The development of models of peripubertal feminizing GAHT is an additional area for future work.
性别肯定激素疗法（GAHT）是许多跨性别和性别多样化（TGD）个体过渡过程中的重要组成部分。多个医学组织建议在开始GAHT之前进行生育力保存咨询；然而，关于GAHT对生育力和生殖功能影响的高质量数据仍然很少。使用布尔搜索运算符进行了PubMed文献综述，链接了“小鼠”、“大鼠”、“灵长类动物”、“动物模型”、“跨性别者”、“性别”、“雌激素”、“睾酮”、“生育力”和“生育力保存”等关键词或短语。最近的研究产生了许多GAHT动物模型，这些模型使用类似的激素方案，并产生与人类患者使用和观察到的类似表型结果。特定于含睾酮（T）的GAHT，动物在治疗后表现出月经周期丧失，治疗停止后月经恢复，促性腺激素水平受到抑制，以及阴蒂肥大等身体变化。模仿青春期前跨男性个体GAHT的模型表明，GnRHa治疗预处理不会改变随后T给药的效果，这与成年模型中描述的效果相似。两种模型都表明，停止T治疗后未来生育力有很大潜力。对于含雌二醇（E）的GAHT，动物表现出睾丸、附睾和精囊尺寸减小，以及生精细胞持续产生和生精小管空泡化。鉴于在该领域进行人体研究面临伦理挑战，高保真动物模型代表了一个有前景的研究机会，并最终可能改变关于生育力保存必要性的临床咨询。未来的研究应更好地描述剂量和持续时间等治疗属性与生殖紊乱可逆程度之间的相互作用（如果存在的话）。青春期前女性化GAHT模型的开发是未来工作的另一个领域。
