DATA Science Department, Santé publique France, Saint Maurice 94415, France.
Non-Transmissible Diseases and Injury Department, Santé publique France, Saint Maurice 94415, France.
Hum Reprod. 2021 Apr 20;36(5):1383-1394. doi: 10.1093/humrep/deaa378.
Is there an evolution in the risk of operated cryptorchidism in France and does local geographical environment appear as an important trigger for this defect?
We observed an increase of the risk of operated cryptorchidism in boys under the age of 7 years during the period 2002-2014 and a strong spatial heterogeneity, with the detection of spatial clusters suggesting environmental factors.
Epidemiologic data on cryptorchidism are scarce and its etiology is poorly understood. As part of the testicular dysgenesis syndrome, cryptorchidism is suspected to be a male genital developmental disorder caused by endocrine disruptor chemical (EDC) exposure during the prenatal period.
STUDY DESIGN, SIZE, DURATION: This was a retrospective and descriptive study using data from the French national hospital discharge database, in the 2002-2014 study period. We built an indicator to reflect incident cases of operated cryptorchidism in boys under the age of 7 years in metropolitan France, with an algorithm using specific codes for diseases (ICD-10 codes) and surgical acts (CCAM codes).
PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population was composed of 89 382 new cases of operated cases of cryptorchidism in boys under the age of 7 years. We estimated the temporal evolution of the incidence rate. We fitted a spatial disease-mapping model to describe the risk of cryptorchidism at the postcode scale. We used Kulldorff's spatial scan statistic and Tango's flexibly shaped spatial scan statistic to identify spatial clusters.
The estimated increase in the incidence of operated cryptorchidism from 2002 to 2014 was equal to 36.4% (30.8%; 42.1%). Cryptorchidism displayed spatial heterogeneity and 24 clusters (P < 0.0001) were detected. The main cluster was localized in a former coal mining and metallurgic area in northern France, currently an industrial area. The cluster analysis suggests the role of shared socio-economic and environmental factors that may be geographically determined and intertwined. The industrial activities identified in the clusters are potentially the source of persistent environmental pollution by metals, dioxins and polychlorinated biphenyls.
LIMITATIONS, REASONS FOR CAUTION: The indicator we used reflects operated cases of cryptorchidism, with an under-evaluation of the health problem. We cannot exclude a possible role of the evolution and local differences in surgical practices in the observed trends. Our inclusion of boys under 7 years of age minimized the biases related to differences in practices according to age. Regarding the environmental hypothesis, this is an exploratory study and should be considered as a hypothesis-generating process for future research studies.
To our knowledge, this is the first descriptive study to address nationwide trends of operated cryptorchidism with detection of spatial clusters, with a very large sample allowing great statistical power. Our results generate plausible environmental hypotheses, which need to be further tested.
STUDY FUNDING/COMPETING INTEREST(S): This study was entirely funded by Santé publique France, the French National Public Health Agency. All authors declare they have no actual or potential competing financial interest.
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法国手术治疗隐睾症的风险是否存在演变，当地的地理环境是否是导致这种缺陷的重要诱因？
我们观察到，2002-2014 年期间，7 岁以下男孩手术治疗隐睾症的风险增加，且存在强烈的空间异质性，空间聚类的检测提示存在环境因素。
隐睾症的流行病学数据很少，其病因也知之甚少。作为睾丸发育不良综合征的一部分，隐睾症被怀疑是一种男性生殖器发育障碍，是由于产前暴露于内分泌干扰化学物质（EDC）引起的。
研究设计、规模、持续时间：这是一项回顾性和描述性研究，使用了法国国家医院出院数据库 2002-2014 年期间的数据。我们建立了一个指标，以反映法国大都市地区 7 岁以下男孩手术治疗隐睾症的新发病例，该指标使用特定疾病（ICD-10 代码）和手术行为（CCAM 代码）的算法。
参与者/材料、设置、方法：研究人群由 89382 名新诊断为 7 岁以下男孩手术治疗隐睾症的患者组成。我们估计了发病率的时间演变。我们拟合了一个空间疾病映射模型来描述隐睾症在邮政编码尺度上的风险。我们使用 Kulldorff 的空间扫描统计和 Tango 的灵活形状空间扫描统计来识别空间聚类。
2002 年至 2014 年，手术治疗隐睾症的发病率估计增加了 36.4%（30.8%；42.1%）。隐睾症存在空间异质性，检测到 24 个聚类（P<0.0001）。主要聚类位于法国北部一个前采煤和冶金区，现为工业区。聚类分析提示了共同的社会经济和环境因素的作用，这些因素可能在地理上是确定的和相互交织的。在聚类中确定的工业活动可能是金属、二恶英和多氯联苯等持续环境污染的来源。
局限性、谨慎的原因：我们使用的指标反映了手术治疗的隐睾症病例，对健康问题的评估不足。我们不能排除手术实践的演变和当地差异在观察到的趋势中可能发挥的作用。我们将 7 岁以下的男孩纳入研究范围，最大限度地减少了与年龄相关的实践差异带来的偏倚。关于环境假设，这是一项探索性研究，应被视为未来研究的假设生成过程。
据我们所知，这是第一项描述性研究，涉及全国范围内手术治疗隐睾症的趋势，并检测到空间聚类，样本量非常大，统计能力很强。我们的结果产生了合理的环境假说，需要进一步验证。
研究资金/利益冲突：本研究完全由法国公共卫生署（Santé publique France），即法国国家公共卫生机构资助。所有作者均声明他们没有实际或潜在的利益冲突。
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