Abstract
BackgroundSex hormones closely regulate development of the male genital organs during fetal life. The hypothesis that xenobiotics may disrupt endogenous hormonal signalling has received considerable scientific attention, but human evidence is scarce.ObjectivesWe analyse occurrence of hypospadias and cryptorchidism according to maternal and paternal occupational exposure to possible endocrine disrupting chemicals.MethodsWe conducted a follow-up study of 45,341 male singleton deliveries in the Danish National Birth Cohort during 1997-2009. Information on work during pregnancy was obtained by telephone interviews around gestational week 16. Parents' job titles were classified according to DISCO-88. A job exposure matrix for endocrine disrupting chemicals (EDCs) was implemented to assess occupational exposures. The Medical Birth and National Hospital Register provided data on congenital anomalies diagnosed at birth or during follow-up, which ended in 2009. Crude and adjusted hazard ratios (HR) were obtained from Cox regression models.ResultsAmong all pregnancies, 6.3% were classified as possibly or probably exposed to EDCs. The most prevalent occupations conferring possible exposure were cleaners, laboratory technicians, hairdressers and agricultural workers (58% of all potentially exposed). The final cumulative incidence of cryptorchidism in boys was 2.2% (1002 cases), and of hypospadias 0.6% (262 cases). The occurrence of hypospadias increased when mothers were probably [HRa = 1.8 (95% CI 1.0-2.6)] or possibly exposed to one or more EDCs [HRa = 2.6 (95% CI 1.8-3.4). Possible paternal exposure to heavy metals increased the risk of hypospadias [HRa 2.2 (95% CI: 1.0-3.4)] and cryptorchidism [HRa 1.9 (95% CI: 1.1-2.7)]. None of the exposure groups reached statistical significance.ConclusionThe study provides some but limited evidence that occupational exposure to possible endocrine disrupting chemicals during pregnancy increases the risk of hypospadias.
Highlights
Sex hormones closely regulate development of the male genital organs during fetal life
Fetal exposure to chemicals with anti-androgen or estrogen-like activity may interfere with normal hormonal signalling, which may increase the risk of cryptorchidism, hypospadias and other male reproductive disorders [12,13]
We examine occupational exposure to potentially endocrine disrupting compounds, utilizing data from a large Danish National Birth Cohort
Summary
Sex hormones closely regulate development of the male genital organs during fetal life. There are indications that the prevalence of cryptorchidism and hypospadias increased from the 60s to the 80s in Europe and in the USA, data providing this information have important methodological limitations [8,9,10]. The fetal development of the male reproductive organs is controlled by sex hormones, and in particular androgens play a crucial role during the first trimester of pregnancy [11]. Fetal exposure to chemicals with anti-androgen or estrogen-like activity may interfere with normal hormonal signalling, which may increase the risk of cryptorchidism, hypospadias and other male reproductive disorders [12,13]
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