Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Hum Reprod. 2020 Aug 1;35(8):1765-1780. doi: 10.1093/humrep/deaa127.
Is there a difference in testicular function in early adulthood between men born with cryptorchidism and men born with normally descended testes?
In men from the general population, a history of cryptorchidism was associated with lower total testis volume and impaired semen quality as well as altered serum levels of reproductive hormones.
The association between cryptorchidism and testicular function is well documented in studies based on sub-fertile or infertile men recruited from a clinical setting. However, the association has not previously been investigated in men from the general population, who were unselected regarding fertility status.
STUDY DESIGN, SIZE, DURATION: This is a cross-sectional population-based study of 6376 young Danish men examined from 1996 to 2017.
PARTICIPANTS/MATERIALS, SETTING, METHODS: This study is based on young men from the greater Copenhagen area, Denmark (median age of 19 years) who were unselected regarding fertility status and semen quality. The young men delivered a semen sample, had a blood sample drawn and underwent a physical examination including assessment of testis volume. Participants completed a questionnaire regarding cryptorchidism at birth, current lifestyle and their mother's pregnancy, after consulting their mother. The differences in markers of testicular function, including testis volume, semen parameters and reproductive hormones between men with and without a history of cryptorchidism were investigated with multiple linear regression analyses.
The participation rate was 24% for the entire study period. Overall, a history of cryptorchidism was associated with reduced testicular function. In the adjusted models, a history of cryptorchidism was associated with a 3.5 ml lower total testis volume, determined by orchidometer (P < 0.001), 28% lower sperm concentration (95% CI: -37 to -20) and 26% lower inhibin B/FSH ratio (95% CI: -50 to -22) compared to men without a history of cryptorchidism, suggesting a reduced spermatogenetic capacity. Men with a history of cryptorchidism also had a slightly reduced Leydig cell function expressed as a 6% lower testosterone/LH ratio (95% CI: -12 to -0.7). The significant effect sizes and different markers of testicular function pointing in the same direction across the different models based on a large sample size support that the results are not chance findings.
LIMITATIONS, REASONS FOR CAUTION: Information on cryptorchidism at birth and treatment modus was obtained by retrospective self-report, and each participant only delivered one semen sample.
The results suggest that men with a history of cryptorchidism could be at increased risk of experiencing fertility problems. However, among these men there is a wide variation in semen quality and further research is needed in order to identify the subgroup of boys born with cryptorchidism who are at the greatest risk of impaired semen quality when reaching adulthood.
STUDY FUNDING/COMPETING INTEREST(S): The study received financial support from the Research fund of Rigshospitalet, Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603. FP7/2007-2013, DEER Grant agreement no. 212844); the Danish Ministry of Health; the Danish Environmental Protection Agency; A.P. Møller and wife Chastine McKinney Møllers Foundation; and Svend Andersens Foundation. None of the founders had any role in the study design, collection, analysis or interpretation of data, writing of the paper or publication decisions. The authors have nothing to declare.
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患有隐睾症的男性与正常下降的睾丸的男性在成年早期的睾丸功能是否存在差异？
在普通人群中，隐睾症病史与总睾丸体积较小、精液质量受损以及生殖激素血清水平改变有关。
在基于不育或不孕的男性的研究中，隐睾症与睾丸功能之间的关联已有充分的文献记载，这些男性是从临床环境中招募的。然而，之前尚未在来自普通人群的男性中研究过这种关联，这些男性在生育能力方面没有选择。
研究设计、规模、持续时间：这是一项基于丹麦哥本哈根地区的 6376 名年轻丹麦男性的横断面人群研究，这些男性在 1996 年至 2017 年期间接受了检查。
参与者/材料、设置、方法：本研究基于丹麦哥本哈根地区的年轻男性（中位年龄 19 岁），他们在生育能力和精液质量方面没有选择。这些年轻男性提供了精液样本，抽取了血液样本，并进行了体检，包括评估睾丸体积。参与者在咨询母亲后，填写了关于出生时隐睾症、当前生活方式和母亲怀孕情况的问卷。通过多元线性回归分析，研究了患有和不患有隐睾症的男性之间睾丸功能标志物（包括睾丸体积、精液参数和生殖激素）的差异。
整个研究期间的参与率为 24%。总体而言，隐睾症病史与睾丸功能降低有关。在调整后的模型中，与没有隐睾症病史的男性相比，隐睾症病史与睾丸体积减少 3.5 毫升（经睾丸计测定，P<0.001）、精子浓度降低 28%（95%CI：-37 至-20）和抑制素 B/FSH 比值降低 26%（95%CI：-50 至-22）有关，这表明生精能力降低。患有隐睾症的男性的睾丸间质细胞功能也略有降低，表现为睾酮/黄体生成素比值降低 6%（95%CI：-12 至-0.7）。基于大量样本量的不同模型中指向同一方向的显著效应大小和不同的睾丸功能标志物支持这些结果并非偶然发现。
局限性、谨慎的原因：出生时隐睾症和治疗方式的信息是通过回顾性自我报告获得的，每个参与者仅提供了一份精液样本。
这些结果表明，患有隐睾症的男性可能面临更高的生育问题风险。然而，在这些男性中，精液质量存在很大差异，需要进一步研究，以便确定出生时患有隐睾症的男孩中哪些亚组在成年后精液质量受损的风险最大。
研究基金/利益冲突：该研究得到了哥本哈根大学医院 Rigshospitalet 研究基金、欧盟（合同编号 BMH4-CT96-0314、QLK4-CT-1999-01422、QLK4-CT-2002-00603、FP7/2007-2013、DEER 资助协议号 212844）、丹麦卫生部、丹麦环境保护局、A.P. 穆勒和妻子 Chastine McKinney 穆勒基金会以及 Svend 安德生基金会的支持。这些创始人在研究设计、数据收集、分析或解释、论文撰写或出版决策方面均无任何作用。作者没有任何声明。
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