Time and spatial trends of operated cryptorchidism in France and environmental hypotheses: a nationwide study from 2002 to 2014

Abstract

STUDY QUESTION 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? SUMMARY ANSWER 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. WHAT IS KNOWN ALREADY 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. MAIN RESULTS AND THE ROLE OF CHANCE 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. WIDER IMPLICATIONS OF THE FINDINGS 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. TRIAL REGISTRATION NUMBER N/A.

The epidemiology of cryptorchidism and potential risk factors, including endocrine disrupting chemicals

“…Overall, the identified clusters with higher incidences of cryptorchidism were characterized by more dense industrial activities. Such differences could be related to socioeconomic status of the inhabitants but adjusting the spatial analyses for deprivation index did not change the results, suggesting a role of pollution related to former and prior industry ( 22 ). Similarly, incidences of cryptorchidism in Korea were shown to be higher in industrialized areas ( 47 ).…”

“…Finally, data from Italy covering births from 1978-1997 suggest a modest decline in prevalence when stratifying across the time periods: 4.3% in 1978-1987 vs. 2.7% in 1988-1997 ( 15 ) ( Figure 1B ). In France the incidence rate of orchiopexy increased from 2.2 per 1000 in 2002 to 2.8 per 1000 in 2014 corresponding to a 36% increase within this period ( 22 ). Reasons for these temporal differences remain unclear, however, environmental factors, including differences in prenatal exposures to endocrine disruptors has been suggested as one contributing factor.…”

Using Experimental Models to Decipher the Effects of Acetaminophen and NSAIDs on Reproductive Development and Health

“…Exposure to environmental endocrine disruptors has been associated with the occurrence of hypospadias and micropenis in male neonates ( Raghavan et al, 2018 ; Gaspari et al, 2021 ) and with puberty disorders in girls ( Sultan et al, 2018 ). Epidemiology studies on cryptorchidism occurrence in France in the last 12 years ( n = 89,000 boys undergoing surgery for cryptorchidism), revealed an increase in its incidence by 36% that may be linked to geographically determined environmental factors ( Le Moal et al, 2021 ).…”

The adverse role of endocrine disrupting chemicals in the reproductive system

“…However, in the French West, there was no observed association between maternal or cord plasma concentration of Chlordecone, an organochlorine pesticide, and the risk of overall malformations or undescended testes ( 349 ). Cryptorchidism displayed spatial heterogeneity, with the main cluster in an area of former coal mining and metallurgic industry in northern France, suggesting environmental factors associated with higher incidence ( 350 ). Nevertheless, the research results on the relationship between EDCs and cryptorchidism are not consistent.…”