The incidence of many hormone-dependent diseases, including testicular cancer, have sharply increased in all high-income countries during the 20th century. This is not fully explained by established risk factors. Concurrent, increasing exposure to antiandrogenic environmental endocrine disrupting chemicals (EDCs) in fetal life may partially explain this trend. This systematic review assessed available evidence regarding the association between environmental EDC exposure and risk of testicular cancer (seminomas and non-seminomas). Following PRISMA guidelines, a search of English peer-reviewed literature published prior to December 14 th, 2020, in the databases PubMed and Embase® was performed. Among the 279 identified records, 19 were eligible for quality assessment and 10 for further meta-analysis. The completeness of reporting was high across papers, but over 50% were considered subject to potential risk of bias. Mean age at diagnosis was 31.9 years. None considered effects of EDCs multipollutant mixtures. The meta-analyses showed that maternal exposure to combined EDCs was associated with a higher risk of testicular cancer in male offspring (summary RRs: 2.16, (95% CI:1.78-2.62); 1.93 (95% CI:1.49-2.48); 2.78 (95% CI:2.27-3.41) for all, seminoma, non-seminoma respectively). Similarly, high maternal exposures to grouped organochlorines and organo-halogens were associated with higher risk of seminoma and non-seminoma in the offspring. Summary estimates related to postnatal adult male EDC exposures were inconsistent.Maternal but not postnatal adult male, EDC exposures were consistently associated with a higher risk of testicular cancer, particularly risk of non-seminomas. However, the quality of studies was mixed and considering the fields complexity, more prospective studies of prenatal EDC multipollutant mixture exposures and testicular cancer are needed.

Background: Anogenital distance (AGD), the distance between the anus and genitals, is in rodents a well-established marker of early androgen action and has been suggested to be so in humans as well. Thus, a link between human AGD and semen quality and potentially fecundity may exist. Objective:The aim of this study was to assess the association between AGD and male factor infertility and among proven fertile men also time to pregnancy (TTP).Material and methods: All included men were recruited from and examined at Copenhagen University Hospital -Rigshospitalet, Denmark (N = 388). Men with impaired semen quality were included from infertile couples (N = 128), and men with naturally conceived pregnant partners were invited to participate when their partners had their routine second trimester examination (N = 260). All men underwent a physical examination, completed a questionnaire (including TTP for the fertile men), delivered a semen sample and had a blood sample drawn. The primary exposure was AGD AS measured from the centre of the anus to the posterior base of the scrotum. Associations between AGD and fertility status as well as between AGD and TTP among the fertile men were calculated using multiple logistic regression adjusted for covariates.Results: AGD did not show a statistically significant association with fertility status.In adjusted logistic regression models, the odds of infertility per 1 cm increase in AGD AS were 1.02 (95% confidence interval [CI]: 0.88; 1.19). Among fertile men, a 1cm increase in AGD AS was associated with an 8% non-statistically significantly reduced odds of having a longer (>3months) TTP (adjusted odds ratio (OR) = 0.92, 95% CI: 0.76-1.11). Conclusion:Our study showed that the clinical application of AGD as a predictor of fertility and fecundity seems to be limited as no associations were observed between AGD and fertility status, nor was the decreased risk of experiencing a longer TTP with longer AGD AS statistically significant.

Asthma is driven by an inflammatory response that may impact testicular function. In this cross-sectional study, we investigated the association between self-reported asthma and testicular function (semen parameters, reproductive hormone levels), and determined whether potential further inflammation due to self-reported allergy modified this association. A total of 6177 men from the general population completed a questionnaire including information on doctor-diagnosed asthma or allergy, had a physical examination, delivered a semen sample, and had a blood sample drawn. Multiple linear regression analyses were performed. A total of 656 (10.6%) men reported having ever been diagnosed with asthma. Generally, self-reported asthma was consistently associated with a poorer testicular function; however, few estimates were statistically significant. Specifically, self-reported asthma was associated with statistically significant lower total sperm count [median: 133 vs. 145 million; adjusted β (95% CI): −0.18 (−0.33 to −0.04) million on cubic-root-transformed scale] and borderline statistically significant lower sperm concentration compared with no self-reported asthma. The association between asthma and total sperm count was of similar magnitude among men with and without allergy. In conclusion, men with self-reported asthma had poorer testicular function than men without asthma. However, the cross-sectional design of the study limits ascertainment of causality.