Tornese Gianluca, Di Mase Raffaella, Munarin Jessica, Ciancia Silvia, Santamaria Fabiana, Fava Daniela, Candela Egidio, Capalbo Donatella, Ungaro Carla, Improda Nicola, Diana Pierluigi, Matarazzo Patrizia, Guazzarotti Laura, Toschetti Tommaso, Sambati Vanessa, Tamaro Gianluca, Bresciani Giulia, Licenziati Maria Rosaria, Street Maria Elisabeth, Aversa Tommaso, Delvecchio Maurizio, Faienza Maria Felicia, Iughetti Lorenzo, Calcaterra Valeria, de Sanctis Luisa, Salerno Mariacarolina, Franceschi Roberto
Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy.
Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
Front Endocrinol (Lausanne). 2025 May 14;16:1555186. doi: 10.3389/fendo.2025.1555186. eCollection 2025.
Puberty suppression using gonadotropin-releasing hormone agonists (GnRHa) is a reversible medical intervention that halts endogenous puberty, allowing transgender and gender-diverse (TGD) adolescents to avoid the development of secondary sexual characteristics that may cause psychological distress. This pause in pubertal progression provides time to explore gender identity or facilitates alignment with affirmed gender in those with an established identity. While widely used, long-term evidence on the efficacy and safety of GnRHa in this population remains limited. This systematic review aims to synthesize current data on the benefits and potential risks of GnRHa in TGD adolescents.
We conducted a comprehensive literature search across PubMed, EMBASE, Cochrane Library, and other databases, covering studies published from February 2011 to February 2024. Eligible studies included adolescents under 18 with gender dysphoria or incongruence treated with GnRHa, reporting outcomes related to efficacy or side effects. Fifty-one studies met inclusion criteria, and data on physical health, mental health, bone density, fertility, and adverse events were extracted and assessed using the GRADE approach.
Of the 51 studies, 22 were rated as moderate to high-quality evidence. GnRHa effectively suppressed puberty and secondary sex characteristics. Effects on growth and body composition varied; bone mineral density declined during treatment, particularly in AMAB individuals. Mental health improved significantly, including reduced depression, anxiety, and suicidality-especially when GnRHa was followed by gender-affirming hormone therapy (GAHT). Quality of life improved over time, while body dissatisfaction often persisted during suppression and improved after GAHT or surgery. No moderate- or high-quality evidence was found on fertility, sexual function, or cancer risk.
GnRHa is effective in halting puberty and improving mental health in TGD adolescents. However, key clinical and ethical considerations-such as bone health monitoring, fertility counseling, psychological support, and informed decision-making-must guide treatment. Long-term safety remains uncertain, particularly regarding skeletal health, reproductive outcomes and cancer risk. A precision medicine approach and co-produced longitudinal studies are essential to support safe, individualized care.
https://www.crd.york.ac.uk, identifier CRD42024528334.
使用促性腺激素释放激素激动剂（GnRHa）抑制青春期是一种可逆的医学干预措施，可阻止内源性青春期发育，使跨性别和性别多样化（TGD）青少年避免出现可能导致心理困扰的第二性征。青春期发育的这种暂停为探索性别认同提供了时间，或有助于已确立性别认同的人使其身体特征与所认同的性别相符。虽然GnRHa被广泛使用，但关于其在该人群中的疗效和安全性的长期证据仍然有限。本系统评价旨在综合当前关于GnRHa在TGD青少年中的益处和潜在风险的数据。
我们在PubMed、EMBASE、Cochrane图书馆和其他数据库中进行了全面的文献检索，涵盖2011年2月至2024年2月发表的研究。符合条件的研究包括年龄在18岁以下、患有性别焦虑或性别不一致且接受GnRHa治疗的青少年，并报告与疗效或副作用相关的结果。51项研究符合纳入标准，使用GRADE方法提取并评估了有关身体健康、心理健康、骨密度、生育能力和不良事件的数据。
在这51项研究中，22项被评为中等至高质量证据。GnRHa有效地抑制了青春期和第二性征。对生长和身体成分的影响各不相同；治疗期间骨矿物质密度下降，尤其是在出生时被指定为男性（AMAB）的个体中。心理健康显著改善，包括抑郁、焦虑和自杀倾向降低，尤其是在GnRHa治疗后接受性别确认激素治疗（GAHT）时。随着时间的推移，生活质量有所提高，而身体不满意感在抑制期间通常持续存在，在GAHT或手术后有所改善。未发现关于生育能力、性功能或癌症风险的中等或高质量证据。
GnRHa在阻止TGD青少年青春期发育和改善心理健康方面有效。然而，关键临床和伦理考量，如骨健康监测、生育咨询、心理支持和知情决策，必须指导治疗。长期安全性仍然不确定，特别是在骨骼健康、生殖结局和癌症风险方面。精准医学方法和共同开展的纵向研究对于支持安全、个性化的护理至关重要。
