Schwartz Lauren, Lal M, Cohn J, Mendoza Carrie D, MacMillan Leslie
Oklahoma City Psychiatry: Lauren H. Schwartz MD PLLC, Oklahoma City, USA.
The Killarney Group, Genspect, Offaly, Ireland.
Discov Ment Health. 2025 Jun 12;5(1):88. doi: 10.1007/s44192-025-00216-3.
Efforts to alleviate the psychological distress of gender dysphoria have included the use of exogenous estrogen (often with anti-androgens) to alter secondary sex characteristics of natal males. In response to the rapid increase in presenting cases among young people, extensive scrutiny has now been brought to bear on these medical interventions for minors, with ESCAP reporting "an urgent need for safeguarding clinical, scientific, and ethical standards." However, due to the lack of systematic outcome data, the associated risk-benefit profile is unknown. Several recent systematic reviews have found the evidence of benefit to be of low or very low certainty, while some risks, such as infertility, have been long recognized. This paper compiles several emerging and accumulating safety signals in the medical literature. These range from increased rates of previously associated adverse outcomes with long-term estrogen use (e.g., acute cardiovascular events) to associations of estrogen use with newly identified adverse outcomes. Estrogen also induces changes in the brain, raising concerns for negative impacts on mood (e.g., depression) and cognition. These safety signals indicate the need for further investigation and a thorough systematic search for others, which may now be more evident due to the increased number of young people receiving these treatments. There is an urgent need for the evidence base to be improved with more studies, especially those with systematic long-term follow-up and those that can disentangle possible confounders, as well as systematic reviews to help interpret their reliability.
缓解性别焦虑症心理困扰的努力包括使用外源性雌激素（通常与抗雄激素联合使用）来改变出生时为男性的人的第二性征。鉴于年轻人中前来就诊的病例迅速增加，目前对针对未成年人的这些医学干预措施进行了广泛审查，亚太经社会报告称“迫切需要维护临床、科学和道德标准”。然而，由于缺乏系统的结果数据，相关的风险效益情况尚不清楚。最近的几项系统评价发现，获益证据的确定性很低或非常低，而一些风险，如不孕，早已为人所知。本文汇总了医学文献中几个新出现且不断积累的安全信号。这些信号包括长期使用雌激素之前相关不良后果的发生率增加（如急性心血管事件），以及雌激素使用与新发现的不良后果之间的关联。雌激素还会引起大脑变化，引发对其对情绪（如抑郁）和认知产生负面影响的担忧。这些安全信号表明需要进一步调查，并对其他信号进行全面系统的搜索，由于接受这些治疗的年轻人数量增加，现在可能更明显地需要这样做。迫切需要通过更多研究来改善证据基础，尤其是那些进行系统长期随访的研究以及能够理清可能混杂因素的研究，同时还需要系统评价来帮助解读其可靠性。
