Analgesics During Pregnancy and Cryptorchidism

Jensen, Mads Christian; Henriksen, Tine Brink; Rebordosa, Cristina; Thulstrup, Ane Marie; Toft, Gunnar; Sørensen, Henrik Toft; Bonde, Jens Peter; Olsen, Jørn

doi:10.1097/ede.0b013e31821eca69

Cited by 14 publications

(9 citation statements)

References 7 publications

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“…The anti-androgenic effect of paracetamol in developmentally exposed rats is corroborated by findings of reduced testosterone production in ex vivo fetal rat testes (Kristensen et al 2011(Kristensen et al , 2012 and by in vitro findings in adult human testes (Albert et al 2013). Furthermore, PM exposure during fetal development in humans has also been associated with increased risk of cryptorchidism in several epidemiological studies (Jensen et al 2010, 2011a, Kristensen et al 2011, Snijder et al 2012, indicating that the effects seen in the rats could be indicative of adverse effects in humans. Further examination of endocrine-sensitive endpoints later in life may clarify whether this anti-androgenic effect of paracetamol causes permanent adverse reproductive effects.…”

Section: Discussionsupporting

confidence: 50%

Mixtures of endocrine-disrupting contaminants induce adverse developmental effects in preweaning rats

et al. 2014

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Reproductive toxicity was investigated in rats after developmental exposure to a mixture of 13 endocrine-disrupting contaminants, including pesticides, plastic and cosmetic ingredients, and paracetamol. The mixture was composed on the basis of information about high-end human exposures, and the dose levels reflecting 100, 200, and 450 times this exposure were tested. The compounds were also grouped according to their estrogenicity or anti-androgenicity, and their joint effects were tested at two different doses, with each group reflecting 200 or 450 times human exposure. In addition, a single paracetamol dose was tested (350 mg/kg per day). All exposures and a vehicle were administered by oral gavage to time-mated Wistar dams rats throughout gestation and lactation, and their offspring were assessed for reproductive effects at birth and in prepuberty. The mixture doses, which included the anti-androgenic compounds, affected the male offspring by causing decreased anogenital distance, increased nipple retention (NR), and reduced ventral prostate weights, at both medium and high doses. In addition, the weights of the levator ani/bulbocavernosus muscle (LABC) were decreased at the high dose of anti-androgen mixture. No effects were seen after exposure to the estrogenic chemicals alone, whereas males exposed solely to paracetamol showed decreased LABC weights and increased NR. Thus adverse reproductive effects were observed at mixtures reflecting 200 times high-end human exposure, which is relatively close to the safety margin covered by the regulatory uncertainty factor of 100. This suggests that highly exposed human population groups may not be sufficiently protected against mixtures of endocrine-disrupting chemicals.

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Section: Discussionsupporting

confidence: 50%

Mixtures of endocrine-disrupting contaminants induce adverse developmental effects in preweaning rats

et al. 2014

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“…14 Several prenatal exposures have been evaluated by aggregating data from these cohorts with cryptorchidism end points from the DNPR, including maternal alcohol consumption, tobacco smoking, use of weak analgesics, pregnancy levels of alphafetoprotein and parental occupational exposures to potentially endocrine disrupting chemicals. [15][16][17][18][19][20][21][22] Despite these research efforts, less attention has been given to the validity of the registry data on cryptorchidism. 23 Validity reflects the probability of being registered given that one has cryptorchidism, and the probability of having cryptorchidism given that one is registered.…”

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confidence: 98%

Accuracy of Cryptorchidism Diagnoses and Corrective Surgical Treatment Registration in the Danish National Patient Registry

et al. 2012

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“…For example, Jensen et al.,(2010) reported near-identical crude and adjusted HRs despite adjusting for a number of potential confounders. The authors also conducted multiple sensitivity analyses with further potential confounders to their models, but again observed very little variation in terms of association strength (Jensen et al, 2011). This suggests that the relationship between analgesia use and risk of cryptorchidism is not noticeably affected by confounding.…”

Section: Discussionmentioning

confidence: 99%

Analgesia use during pregnancy and risk of cryptorchidism: a systematic review and meta-analysis

et al. 2017

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Study question Are boys who are born to mothers who use analgesics during pregnancy at increased risk of cryptorchidism compared to those born to mothers who do not take analgesia? Summary answer In this systematic review and meta-analysis of 10 published studies, we observed only weak evidence of an association between analgesia use during pregnancy and risk of cryptorchidism in the son. What is known already Concentrations of analgesia relevant to human exposure have been implicated as causing endocrine disturbances in the developing foetal testis. However, when viewed collectively there appears to be conflicting evidence regarding an association between maternal use of analgesics and development of cryptorchidism. Study design, size, duration A systematic review and meta-analysis of studies on analgesia use during pregnancy and risk of cryptorchidism was performed. The search terms used were (analges* OR paracetamol OR acetaminophen) AND (cryptorchidism OR cryptorchism OR undescended test* OR non-descended test* OR non descended test*) for the databases Ovid Medline, Embase, Scopus and Web of Science. The search included all published articles up until 23rd May 2016 and no limits were set in terms of language. Participants/materials, setting, methods Abstracts were screened by one reviewer to remove irrelevant studies, with a 10% random sample of these verified by a second reviewer. The full text of all remaining papers was obtained and assessed by two reviewers to identify those which met our inclusion criteria. Abstracts included in the final analysis included studies which reported associations between the exposure (analgesia) and the outcome (cryptorchidism), with no limit on study design. Studies were only included if data was provided from which summary associations (odds ratios or relative risks) and their 95% confidence limits could be calculated, or if these summary associations were provided by the authors themselves. For each included study, two reviewers (JG and VS) independently extracted study meta-data in line with PRISMA recommendations. We assessed study quality and potential for bias using the criteria outlined in the Newcastle-Ottawa Quality Assessment Scale, but did not determine a quality score. Two reviewers independently assessed study quality against these criteria. Main results and the role of chance After screening 350 manuscripts, 10 were included in our review (five case-control studies, five cohort studies). We observed weak evidence of an association between ever-use of analgesia and risk of cryptorchidism (pooled crude odds ratio (OR): 1.11, 95% CI 1.00-1.23), with case-control studies revealing a marginally stronger association (1.23, 95% CI 0.85-1.78) than cohort studies (1.09, 95% CI 0.97-1.22). We observed weak evidence of a dose-response relationship between increasing weeks of analgesia exposure and risk of cryptorchidism, as well as weak evidence of an effect of timing on analgesia exposure and risk of cryptorchidism. Assessment of study quality via the Newcast...

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Analgesics During Pregnancy and Cryptorchidism

Cited by 14 publications

References 7 publications

Mixtures of endocrine-disrupting contaminants induce adverse developmental effects in preweaning rats

Mixtures of endocrine-disrupting contaminants induce adverse developmental effects in preweaning rats

Accuracy of Cryptorchidism Diagnoses and Corrective Surgical Treatment Registration in the Danish National Patient Registry

Analgesia use during pregnancy and risk of cryptorchidism: a systematic review and meta-analysis

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