Inserm (Institut National de la Santé et de la Recherche Médicale) UMR 1085, IRSET (Institut de Recherche Santé Environnement & Travail), Campus de Beaulieu, Avenue du Général Leclerc Bât 13, Université de Rennes 1, Rennes Cedex F-35042, France.
Hum Reprod. 2013 Jul;28(7):1974-86. doi: 10.1093/humrep/det111. Epub 2013 May 12.
Is there evidence at the population level of associations between different male genital disorders, outside Scandinavian countries?
At an international scale, there is evidence for a number of correlations between rates of four male reproductive disorders (hypospadias, cryptorchidism, testicular cancer and low sperm concentration).
Some associations between these outcomes have been shown in studies focusing on individuals and mainly in Nordic European countries. These associations, together with histological evidence of a dysgenesis pattern in testicular tissue specimens, have generated the concept of the existence of a 'testicular dysgenesis syndrome' originating in utero.
STUDY DESIGN, SIZE, DURATION: This is a geographical correlation study using cancer, malformations rates and sperm quality data collected between the years 1998 and 2005.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Incidence rates of testicular cancer were extracted from International Agency for Research on Cancer registries and Globocan, while cryptorchidism and hypospadias prevalence rates were obtained from EUROCAT and International Clearinghouse for Birth Defects Surveillance and Research registries. Sperm concentration data were extracted from recent studies using standardized methodology. A total of 39 registries and 9 sperm studies were selected. Non-parametric Spearman correlation tests were used to test the association between these four disorders. Correlations were computed for all registries together, for registries with high-quality matching coverage only and by continents. Sensitivity analyses were also conducted using data from prospective clinical studies to take into account potential bias related mainly to ascertainment of malformation rates.
We found positive correlations between testicular cancer and hypospadias (r = 0.32, P = 0.05) and between hypospadias and cryptorchidism (r = 0.70, P = 0.008). Stronger correlations were observed when using registries with high-quality matching coverage. Among these registries, differences between Europe and the rest of the world appeared (the positive correlation between testicular cancer and cryptorchidism was stronger outside Europe, r = 0.83, P = 0.01 compared with 0.40, P = 0.60 for European registries). A negative correlation between testicular cancer and sperm concentration was observed (r = -0.88, P = 0.002). These correlations support our initial hypothesis but remain only suggestive due to the intrinsic limitations in the study design (i.e. geographical correlation study) and do not allow causal inference.
LIMITATIONS, REASONS FOR CAUTION: Differences in the ascertainment of malformations rates (definition, length of follow-up) make the international comparison difficult. The small number of registries for some conditions (cryptorchidism) or of studies (for sperm quality) and the absence of information about major risk factors such as ethnicity and socioeconomic status in the registries are also limitations.
Our findings are in agreement with results of studies focusing on individuals and suggest that shared risk factors are present in the populations studied.
在斯堪的纳维亚国家以外的地区，是否有证据表明不同男性生殖器疾病之间存在关联？
在国际范围内，有证据表明四种男性生殖障碍（尿道下裂、隐睾、睾丸癌和精子浓度低）之间存在一定的相关性。
一些研究主要集中在个体，并主要在北欧国家，已经表明了这些结果之间的一些关联。这些关联，以及睾丸组织标本发育不良模式的组织学证据，产生了“睾丸发育不良综合征”这一概念，该综合征起源于子宫内。
研究设计、规模和持续时间：这是一项地理相关性研究，使用了 1998 年至 2005 年间收集的癌症、畸形率和精子质量数据。
参与者/材料、地点、方法：睾丸癌的发病率从国际癌症研究机构登记处和全球癌症观察站提取，而隐睾症和尿道下裂的流行率从欧洲先天性畸形监测中心和国际出生缺陷监测和研究信息中心登记处获得。精子浓度数据从使用标准化方法的最近研究中提取。共选择了 39 个登记处和 9 个精子研究。使用非参数 Spearman 相关检验来检验这四种疾病之间的关联。对所有登记处、具有高质量匹配覆盖的登记处以及按大陆进行了相关性计算。还使用前瞻性临床研究的数据进行了敏感性分析，以考虑主要与畸形率确定相关的潜在偏倚。
我们发现睾丸癌与尿道下裂（r = 0.32，P = 0.05）和尿道下裂与隐睾症（r = 0.70，P = 0.008）之间存在正相关。当使用具有高质量匹配覆盖的登记处时，观察到更强的相关性。在这些登记处中，欧洲和世界其他地区之间出现了差异（睾丸癌和隐睾症之间的正相关关系在欧洲以外地区更强，r = 0.83，P = 0.01，而欧洲登记处为 0.40，P = 0.60）。还观察到睾丸癌和精子浓度之间的负相关（r = -0.88，P = 0.002）。这些相关性支持了我们最初的假设，但由于研究设计（即地理相关性研究）的内在局限性，仍然只是提示性的，并且不能进行因果推断。
局限性、谨慎的原因：畸形率的确定（定义、随访时间）存在差异，使得国际比较变得困难。对于某些情况（隐睾症）或某些研究（精子质量），登记处的数量较少，以及登记处缺乏有关主要风险因素（如种族和社会经济地位）的信息，也是限制因素。
我们的研究结果与主要关注个体的研究结果一致，表明在研究人群中存在共同的风险因素。
