Department of Paediatric Surgery, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Hum Reprod. 2024 Apr 3;39(4):689-697. doi: 10.1093/humrep/deae025.
Do different boys with different types of cryptorchidism exhibit different anogenital distances (AGDs)?
Length of AGD seemed to differ in different groups of patients with cryptorchidism.
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.
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.
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.
The trial was not registered in an ICMJE-recognized trial registry.
不同类型隐睾症的男孩是否表现出不同的肛殖距（AGD）？
似乎不同隐睾症患者群体的 AGD 长度存在差异。
与正常男孩相比，隐睾症男孩的 AGD 往往更短。在尿道下裂、精液质量差的男性和睾丸癌男性中也报告了较短的 AGD。
研究设计、规模、持续时间：这是一项前瞻性描述性队列研究，使用了在单个中心连续选择的 169 名隐睾症男孩的数据（2019 年 9 月至 2022 年 10 月）。
参与者/材料、地点、方法：在麻醉下使用游标卡尺测量 169 名婴儿男孩的 AGD，年龄在 3 至 26 个月之间，根据“婴儿发育与环境研究”（TIDES）和“剑桥婴儿生长研究”的方法，从肛门到阴囊基部（AGDAS）和从肛门到阴茎前基部（AGDAP）测量两个体位的距离，每个患者产生四个平均值（TIDES AGDAS/AP 和 Cambridge AGDAS/AP）。根据我院生长与生殖科对 1940 名健康男婴的大量队列研究，设定了 AGD 的正常年龄值。在隐睾固定术时进行睾丸活检作为临床常规。测量至少 100 个和 250 个横切管的生精细胞数（G/T）和 Ad 精原细胞数（AdS/T），并与正常样本进行比较。通过静脉穿刺采集血液样本，以测量血清 LH、FSH 和抑制素 B。在我院生长与生殖科进行分析，该科也建立了正常参考值。通过 Spearman 秩相关分析评估每个男孩的四个平均 AGD 测量值之间的相关性。将每个男孩的 AGD 测量值转换为年龄的正常 AGD 中位数（MoM）的倍数，并将其命名为 MoM AGD。
104 名男孩行单侧隐睾固定术，47 名男孩行双侧隐睾固定术，18 名男孩患有消失睾丸，其中 1 名男孩双侧睾丸消失。与未下降睾丸相比，消失睾丸的病例中 MoM AGD 高于正常中位数的比例仅为 6%（32%）（P<0.05）。对于消失睾丸的男孩，MoM AGD 随手术年龄增加（Spearman r=0.44），但对于未下降睾丸的男孩，MoM AGD 随手术年龄增加（Spearman r=0.14）。双侧隐睾症男孩的 AGD 较长，且更常患有促性腺激素低下性性腺功能减退症（P<0.005）和（P<0.000001）。
局限性、谨慎原因：尽管这是发表的最大的隐睾症婴儿 AGD 测量材料，但该研究的一个局限性是不同组别的患者数量相当少，这可能降低了统计效力。另一个限制涉及到生精细胞数和 Ad 精原细胞数的正常参考材料稀疏。最后，目前还没有纵向研究评估从出生到成年的 AGD，并评估儿童期 AGD 与生育结果的关系。我们的研究是假设生成的，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。
研究结果与文献一致，即总括的隐睾症男孩组的 AGD 短于正常。然而，有新的发现。与正常男孩和未下降睾丸的男孩相比，消失睾丸的男孩的 AGD 更短。这一发现挑战了目前关于 AGD 在妊娠第 8 至 14 周的“男性化编程窗口”中确定的概念。此外，双侧隐睾症男孩的 AGD 较长，且更常患有促性腺激素低下性性腺功能减退症（P<0.005），这表明促性腺激素低下性性腺功能减退症中胎儿雄激素的缺乏并不那么显著。
研究资金/竞争利益：没有使用外部资金，也没有竞争利益。
该试验未在 ICMJE 认可的试验注册中心注册。
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