To the Editor, We read with interest the letter by Barbar et al. We recognise the clinical scenario described by Barbar et al. of patients with XY gonadal dysgenesis or other types of differences/disorders of sex development (DSD) with a significant risk of germ cell cancer who are hesitant to undergo a prophylactic gonadectomy.¹ Whereas in children the situation is more complex, with parents having to make medical decisions on behalf of their child, adults with DSD can of course decide for themselves to undergo such surgery or not. However, careful counselling and accurate information are essential for patients to be able to make an informed decision. The multidisciplinary DSD team should make sure the individual understands the risk of developing germ cell cancer as well as the chance of remaining function of the gonad with regard to hormone production and fertility. In the patient described by Barbar et al. gonads were afunctional but in prepubertal children there may be some uncertainty about this, and in patients with partial gonadal dysgenesis residual function may vary and needs to be taken into consideration. The consequences of gonadectomy should be explained, that is, the need for and impact of hormone replacement therapy. In addition, the scenario where gonads are left in situ needs to be discussed. In case of afunctional gonads hormone replacement therapy will also be necessary. Periodic monitoring of gonads is recommended but is should be clear that this is aimed at early detection of germ cell cancer rather than preventing germ cell cancer, as premalignant lesions cannot currently be reliably detected through blood tests or imaging. Sertoli cell markers unfortunately are of little help as our recent study showed that germ cell cancer was present in three out of eleven (27%) of those with undetectable serum AMH and inhibin B, which is similar to the 15−40% risk described for gonadal dysgenesis in general.² Although those with very low or undetectable AMH and inhibin B have a lower chance of having any germ cells, the risk of any remaining germ cells to develop into germ cell cancer may be higher because of the severe dysgenesis of the gonads. Lastly, social and cultural factors can also play a role and it is important to identify possible barriers, such as fear of anaesthesia or surgery, or worries about the costs of surgery or need to take leave from work, that may prevent some individuals from undergoing gonadectomy even when they are convinced of the need for the procedure. Peer support as well as psychological counselling may help individuals to weigh all the pros and cons when deciding on a prophylactic gonadectomy.

Currently there is an ongoing international study investigating the practice of gonadectomy in individuals with DSD through the I-DSD registry (https://sdmregistries.org/). We agree with Barbar et al. that to increase knowledge in this field it would be highly valuable to also collect outcome data from individuals that choose to leave their gonads in situ.

致编辑，我们饶有兴趣地阅读了 Barbar 等人的来信。我们认识到 Barbar 等人描述的临床情况。患有 XY 性腺发育不全或其他类型的性发育差异/障碍 (DSD) 且具有显着的生殖细胞癌风险且对接受预防性性腺切除术犹豫不决的患者。¹儿童的情况更为复杂，父母必须代表孩子做出医疗决定，而患有 DSD 的成年人当然可以自行决定是否接受此类手术。然而，仔细的咨询和准确的信息对于患者能够做出明智的决定至关重要。多学科 DSD 团队应确保个人了解患生殖细胞癌的风险以及性腺在激素产生和生育方面保持功能的机会。在 Barbar 等人描述的患者中。性腺功能障碍，但在青春期前的儿童中，这可能存在一些不确定性，并且在部分性腺发育不全的患者中，残余功能可能会有所不同，需要予以考虑。应解释性腺切除术的后果，即激素替代疗法的必要性和影响。此外，还需要讨论性腺留在原位的情况。如果性腺功能障碍，还需要激素替代疗法。建议定期监测性腺，但应该明确的是，这是为了早期发现生殖细胞癌，而不是预防生殖细胞癌，因为目前无法通过血液检查或影像学可靠地检测癌前病变。不幸的是，支持细胞标记物没有什么帮助，因为我们最近的研究表明，在血清 AMH 和抑制素 B 检测不到的患者中，十分之三 (27%) 存在生殖细胞癌，这与 15−40% 的风险描述相似。一般性腺发育不全。²虽然 AMH 和抑制素 B 非常低或检测不到的人拥有生殖细胞的机会较低，但由于性腺严重发育不良，任何剩余生殖细胞发展为生殖细胞癌的风险可能较高。最后，社会和文化因素也可能发挥作用，重要的是要确定可能的障碍，例如对麻醉或手术的恐惧，或担心手术费用或需要请假，这些可能会阻止某些人接受手术即使他们确信需要进行性腺切除术。同伴支持和心理咨询可以帮助个人在决定预防性性腺切除术时权衡所有利弊。

目前正在进行一项国际研究，通过 I-DSD 登记处 (https://sdmregistries.org/) 调查 DSD 患者的性腺切除术实践。我们同意 Barbar 等人的观点。为了增加这一领域的知识，从选择将性腺留在原处的个体收集结果数据将非常有价值。