De Roo C, Schneider F, Stolk T H R, van Vugt W L J, Stoop D, van Mello N M
Department of Reproductive Medicine, Ghent University Hospital, Ghent, Belgium.
Ghent-Fertility and Stem Cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Ghent, Belgium.
Hum Reprod Update. 2025 May 1;31(3):183-217. doi: 10.1093/humupd/dmae036.
Transgender and gender diverse (TGD) people seek gender-affirming care at any age to manage gender identities or expressions that differ from their birth gender. Gender-affirming hormone treatment (GAHT) and gender-affirming surgery may alter reproductive function and/or anatomy, limiting future reproductive options to varying degrees, if individuals desire to either give birth or become a biological parent.
TGD people increasingly pursue help for their reproductive questions, including fertility, fertility preservation, active desire for children, and future options. Their specific needs certainly require more insight into the effects of GAHT on gonads, gametes, and fertility. This systematic review aims to provide an overview of the current knowledge on the impact of GAHT on gonads, gametes, fertility, fertility preservation techniques, and outcomes.
This review was registered in the PROSPERO registry under number CRD42024516133. A literature search (in PubMed, Embase, and Web of Science) was performed with a medical information specialist until 15 November 2024.
In all TGD people using GAHT, histological changes have been reported.Using testosterone GAHT, ovarian cortical and stromal changes were reported by various studies. In most studies, persistent activity in folliculogenesis can be concluded based on the descriptions of the follicle count, distribution, and oocyte retrieval yield. However, there may be a negative effect on the fertilization rate in the presence of testosterone. Reports of successful ovarian stimulation, fertilization, pregnancies, and live births have been published, describing cases with and without testosterone discontinuation.After using oestrogen GAHT, testes are reported to be more atrophic, including smaller seminiferous tubules with heavy hyalinization and fibrosis. Spermatogenic levels varied widely from complete spermatogenesis to meiotic arrest with spermatids, to spermatogonial arrest, Sertoli cells only, or even tubular shadows. Oestrogen and anti-androgen treatment causes higher proportions of sperm abnormalities (i.e. low total sperm count, low sperm concentration, poor sperm motility) or azoospermia. However, after cessation, this may be restored.
Although knowledge of the effect of GAHT is growing, blind spots remain to be uncovered. Therefore, additional research in this specific population is needed, preferably comparing outcomes before and after the start of GAHT. This may help to reveal the pure impact of GAHT on reproductive functioning. Research suggestions also include investigations into the reversibility of the GAHT effect, especially for those who start transition at a young age. Looking carefully at the presented data on GAHT effects on gonads and gametes, the correct advice is to assess and reassess reproductive wishes and preferences repeatedly, and also to explore individual fertility preservation needs during gender-affirming treatment, given the expanding knowledge and therapy opportunities. Finally, concerns regarding long-term health outcomes and quality of life of children born by the use of gametes preserved after exposure to GAHT require prospective follow-up studies.
跨性别者和性别多样化（TGD）人群在任何年龄都寻求性别肯定治疗，以处理与其出生时性别不同的性别认同或表达方式。如果个体希望生育或成为生物学父母，性别肯定激素治疗（GAHT）和性别肯定手术可能会改变生殖功能和/或解剖结构，在不同程度上限制未来的生殖选择。
TGD人群越来越多地就其生殖问题寻求帮助，包括生育力、生育力保存、对孩子的实际渴望以及未来选择。他们的特定需求无疑需要更深入了解GAHT对性腺、配子和生育力的影响。本系统评价旨在概述关于GAHT对性腺、配子、生育力、生育力保存技术及结果影响的现有知识。
本评价在PROSPERO登记库中登记，登记号为CRD42024516133。由医学信息专家在PubMed、Embase和Web of Science中进行文献检索，截至2024年11月15日。
在所有使用GAHT的TGD人群中，均有组织学变化的报道。使用睾酮GAHT时，多项研究报告了卵巢皮质和基质的变化。在大多数研究中，根据卵泡计数、分布及卵母细胞获取产量的描述，可得出卵泡发生持续活跃的结论。然而，在存在睾酮的情况下，可能对受精率有负面影响。已有成功的卵巢刺激、受精、妊娠和活产的报道，描述了停用和未停用睾酮的病例。使用雌激素GAHT后，据报道睾丸萎缩更明显，包括生精小管更小，伴有严重的玻璃样变性和纤维化。生精水平差异很大，从完全生精到减数分裂停滞伴精子细胞，再到精原细胞停滞、仅支持细胞，甚至是小管阴影。雌激素和抗雄激素治疗会导致更高比例的精子异常（即精子总数低、精子浓度低、精子活力差）或无精子症。然而，停药后可能会恢复。
尽管对GAHT效果的认识在不断增加，但仍有盲点有待发现。因此，需要在这一特定人群中开展更多研究，最好比较GAHT开始前后的结果。这可能有助于揭示GAHT对生殖功能的纯粹影响。研究建议还包括调查GAHT效果的可逆性，特别是对于那些在年轻时开始转变的人。仔细研究关于GAHT对性腺和配子影响的现有数据，正确的建议是反复评估和重新评估生殖愿望和偏好，并且鉴于知识和治疗机会的不断增加，在性别肯定治疗期间探索个体的生育力保存需求。最后，对于使用GAHT后保存的配子所生育儿童的长期健康结果和生活质量的担忧需要进行前瞻性随访研究。
