Maternal Use of Acetaminophen, Ibuprofen, and Acetylsalicylic Acid During Pregnancy and Risk of Cryptorchidism

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

doi:10.1097/ede.0b013e3181f20bed

Cited by 168 publications

(137 citation statements)

References 35 publications

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“…Figure 4 Mild analgesic compounds paracetamol and acetylsalicylic acid reduced PGD2 and testosterone production in ex vivo cultured GD14.5 rat supported by an independent Danish study of 47 400 boys with an incidence of cryptorchidism (2%) similar to that observed in the Finnish cohort (Jensen et al, 2010). In that study, they report a significant association between the use of paracetamol in weeks 8-14 and cryptorchidism (Jensen et al, 2010). We did not find an association with hypospadia in any of the birth cohorts; however, the incidence of hypospadia was very low at birth (1% in the Danish and 0.3% in the Finnish cohort) and it is not clear how large the association is between cryptorchidism and hypospadia (Akre and Richiardi, 2009;Jørgensen et al, 2010).…”

Section: Discussionsupporting

confidence: 58%

“…Data represent the mean + SEM. Figure 4 Mild analgesic compounds paracetamol and acetylsalicylic acid reduced PGD2 and testosterone production in ex vivo cultured GD14.5 rat supported by an independent Danish study of 47 400 boys with an incidence of cryptorchidism (2%) similar to that observed in the Finnish cohort (Jensen et al, 2010). In that study, they report a significant association between the use of paracetamol in weeks 8-14 and cryptorchidism (Jensen et al, 2010).…”

Section: Discussionmentioning

confidence: 56%

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Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat

et al. 2010

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 56%

Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat

et al. 2010

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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: Discussionmentioning

confidence: 73%

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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“…The study reported that APAP and prenatal exposure had a higher numbers of baby boys with congenital cryptorchidism. Undescended testes may be linked with alarming risk of testicular germ cell tumors, reduced fertility and psychological adverse events when the baby is grown [17]. Prostaglandins are assumed to be implicated in the differentiation of the testis and the male genital tract [18,19].…”

Section: Cryptorchidism and Acetaminophenmentioning

confidence: 99%

Monster Phase of Acetaminophen Use in Pregnancy: Current Vision of an Old Drug

S.s.¹,

Swaminathan²,

Sambathkumar³

2016

Int J Pharm Pharm Sci

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In various countries, Acetaminophen [APAP] is the frequently used painkiller found in hundreds of medications during pregnancy. It has been broadly used for eras and health care professionals prefer acetaminophen as a choice during pregnancy for relieving pain and fever. Current research reports bothersome inclinations in the rate of acetaminophen exposure and related pregnancy outcome. The exposure of pregnant women to acetaminophen is of great concern. Existing literature evidence shows that acetaminophen exposure during pregnancy may leads to preterm birth, attention deficit hyperactivity disorder (ADHD), autism, male infertility, asthma in pediatrics. Therefore, the prophylactic anticipation of acetaminophen exposure can be a far-sighted approach in order to safeguard humans and wildlife from enduring dangerous effects. This article reviews the epidemiological findings and aims to shed awareness into the second generation outcome of an old drug in pregnant women.

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Maternal Use of Acetaminophen, Ibuprofen, and Acetylsalicylic Acid During Pregnancy and Risk of Cryptorchidism

Abstract: Maternal intake of acetaminophen for more than 4 weeks during pregnancy, especially during the first and second trimesters, may moderately increase the occurrence of cryptorchidism.

Cited by 168 publications

References 35 publications

Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat

Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat

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

Monster Phase of Acetaminophen Use in Pregnancy: Current Vision of an Old Drug

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