STUDY QUESTION Do different boys with different types of cryptorchidism exhibit different anogenital distances (AGDs)? SUMMARY ANSWER Length of AGD seemed to differ in different groups of patients with cryptorchidism. WHAT IS KNOWN ALREADY AGD, which is used as an indicator of prenatal androgen action, tends to be shorter in boys with cryptorchidism compared to unaffected boys. Shorter AGDs have also been reported in boys with hypospadias, in men with poor semen quality, and in men with testicular cancer. STUDY DESIGN, SIZE, DURATION A prospective descriptive cohort study was performed using data from consecutively selected boys with cryptorchidism (n = 169) operated in a single center over a period of 3 years (September 2019 to October 2022). PARTICIPANTS/MATERIALS, SETTING, METHODS AGD was measured in 169 infant boys, at 3 to 26 months of age, during anesthesia with a vernier caliper measuring the distance from the anus to the base of the scrotum (AGDAS) and from the anus to the anterior base of the penis (AGDAP) in two body positions according to the methods by ‘The Infant Development and the Environment Study’ (TIDES) and ‘Cambridge Baby Growth Study’, resulting in four mean values per patient (TIDES AGDAS/AP and Cambridge AGDAS/AP). Normal values for AGD by age were set by our hospital Department of Growth and Reproduction based on a large cohort of healthy infant boys (n = 1940). Testicular biopsies were performed at orchidopexy as a clinical routine. The germ cell number (G/T) and type Ad spermatogonia number (AdS/T) per cross-sectional tubule of at least 100 and 250 tubules, respectively were measured and related to normal samples. Blood samples were obtained by venipuncture for measuring serum LH, FSH, and inhibin B. They were analyzed in our hospital Department of Growth and Reproduction where the normal reference was also established. Correlations between the four mean AGD measurements for each boy were evaluated by Spearman rank correlation analyses. The AGD measurement of every boy was transferred to the multiple of the median (MoM) of the normal AGD for age and named MoM AGD. MAIN RESULTS AND THE ROLE OF CHANCE There were 104 boysoperated for unilateral, and 47 boys operated for bilateral, undescended testes, whereas 18 boys had vanished testis including one boy with bilateral vanished testes. Only 6% of cases with vanished testes had a MoM AGD higher than the normal median compared to 32% with undescended testes (P < 0.05). MoM AGD increased with the age at surgery for boys with vanished testis (Spearman r = 0.44), but not for boys with undescended testes (Spearman r = 0.14). Boys with bilateral cryptorchidism had longer AGDs and more often had hypogonadotropic hypogonadism than boys with unilateral cryptorchidism (P < 0.005) and (P < 0.000001). LIMITATIONS, REASONS FOR CAUTION Although being the largest published material of AGD measurements of infant boys with cryptorchidism, one limitation of this study covers the quite small number of patients in the different groups, which may decrease the statistical power. Another limitation involves the sparse normal reference material on G/T and AdS/T. Finally, there are currently no longitudinal studies evaluating AGD from birth to adulthood and evaluating childhood AGD in relation to fertility outcome. Our study is hypothesis generating and therefore the interpretation of the results should be regarded as exploratory rather than reaching definite conclusions. WIDER IMPLICATIONS OF THE FINDINGS The study findings are in agreement with literature as the total included group of boys with cryptorchidism exhibited shorter than normal AGDs. However, new insights were demonstrated. Boys with vanished testis had shorter AGDs compared to unaffected boys and to boys with undescended testes. This finding challenges the current concept of AGD being determined in ‘the masculinization programming window’ in Week 8 to 14 of gestation. Furthermore, boys with bilateral cryptorchidism had longer AGDs and more often had hypogonadotropic hypogonadism than boys with unilateral cryptorchidism, suggesting that the lack of fetal androgen in hypogonadotropic hypogonadism is not that significant. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used and no competing interests are declared. TRIAL REGISTRATION NUMBER The trial was not registered in an ICMJE-recognized trial registry.

中文翻译：

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169 名单侧或双侧隐睾男孩的肛门生殖器距离，其中 18 名男孩患有睾丸消失

研究问题 患有不同类型隐睾的不同男孩是否表现出不同的肛门生殖器距离 (AGD)？摘要答案 不同隐睾患者组的 AGD 持续时间似乎有所不同。已知的情况 AGD 被用作产前雄激素作用的指标，与未受影响的男孩相比，隐睾男孩的 AGD 往往较短。据报道，患有尿道下裂的男孩、精液质量差的男性以及患有睾丸癌的男性的 AGD 也较短。研究设计、规模、持续时间 使用连续选择的隐睾男孩 (n = 169) 的数据进行了一项前瞻性描述性队列研究，该男孩在 3 年期间（2019 年 9 月至 2022 年 10 月）在单一中心进行手术。参与者/材料、环境、方法 对 169 名 3 至 26 个月大的男婴进行 AGD 测量，在麻醉期间用游标卡尺测量从肛门到阴囊底部 (AGDAS) 以及从肛门到阴囊底部的距离。根据“婴儿发育和环境研究”(TIDES) 和“剑桥婴儿生长研究”的方法，在两种体位下测量阴茎前基部 (AGDAP)，得出每位患者的四个平均值 (TIDES AGDAS/AP 和剑桥 AGDAS/AP）。按年龄划分的 AGD 正常值是由我们医院生长和生殖部门根据一大群健康男婴（n = 1940）设定的。作为临床常规，在睾丸固定术中进行睾丸活检。分别测量至少 100 个和 250 个小管的每个横截面小管的生殖细胞数 (G/T) 和 Ad 型精原细胞数 (AdS/T)，并与正常样本相关。通过静脉穿刺采集血样，测定血清LH、FSH和抑制素B。在我院生长与生殖科进行分析，并建立正常参考值。通过斯皮尔曼等级相关分析评估每个男孩的四次平均 AGD 测量值之间的相关性。将每个男孩的 AGD 测量值转换为年龄正常 AGD 中位数 (MoM) 的倍数，命名为 MoM AGD。主要结果和机会的作用 104 名男孩接受了单侧睾丸手术，47 名男孩接受了双侧睾丸未降手术，而 18 名男孩睾丸消失，其中 1 名男孩双侧睾丸消失。只有 6% 的睾丸消失病例的 MoM AGD 高于正常中位数，而睾丸未降病例的这一比例为 32%（P < 0.05）。对于睾丸消失的男孩，MoM AGD 随着手术年龄的增加而增加 (Spearman r = 0.44)，但对于睾丸未降的男孩则不然 (Spearman r = 0.14)。与单侧隐睾男孩相比，双侧隐睾男孩的 AGD 较长，且更常患有低促性腺激素性性腺功能减退症 (P < 0.005) 和 (P < 0.000001)。局限性和注意理由 虽然是隐睾男婴 AGD 测量的最大出版材料，这项研究的一个局限性在于不同组中的患者数量相当少，这可能会降低统计功效。另一个限制涉及 G/T 和 AdS/T 上的稀疏正态参考材料。最后，目前还没有纵向研究评估从出生到成年的 AGD 以及评估儿童 AGD 与生育结果的关系。我们的研究是假设生成，因此对结果的解释应被视为探索性的，而不是得出明确的结论。研究结果的更广泛意义 该研究结果与文献一致，因为所有隐睾男孩组的 AGD 都比正常男孩短。然而，新的见解得到了证明。与未受影响的男孩和睾丸未降的男孩相比，睾丸消失的男孩的 AGD 较短。这一发现挑战了当前 AGD 的概念，该概念是在妊娠第 8 至 14 周的“男性化编程窗口”确定的。此外，与单侧隐睾男孩相比，双侧隐睾男孩的 AGD 更长，并且更容易出现低促性腺激素性性腺功能减退症，这表明低促性腺激素性性腺功能减退症中胎儿雄激素的缺乏并不那么重要。研究资助/竞争利益 未使用外部资助，也未声明竞争利益。试验注册号 该试验未在 ICMJE 认可的试验登记处注册。