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Prenatal exposure to antifungal medication may change anogenital distance in male offspring: a preliminary study

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Mogensen, Djamilla Madelung ; Pihl, Maria Bergkvist ; Skakkebæk, Niels E ; Andersen, Helle Raun ; Juul, Anders ; Kyhl, Henriette Boye ; Swan, Shanna ; Kristensen, David Møbjerg ; Andersen, Marianne Skovager ; Lind, Dorte Vesterholm ; Jensen, Tina Kold. / Prenatal exposure to antifungal medication may change anogenital distance in male offspring : a preliminary study. I: Environmental Health: A Global Access Science Source. 2017 ; Bind 16, Nr. 1. s. 68.

Bibtex

@article{09c72519936b44a6a06c107d42ccc338,
title = "Prenatal exposure to antifungal medication may change anogenital distance in male offspring: a preliminary study",
abstract = "BACKGROUND: Vaginal candidiasis is frequent among pregnant women and it is treated with anti-fungal medication (conazoles). Conazoles have anti-androgenic properties and prenatal exposure in rodents is associated with a shorter (less masculine) anogenital distance (AGD) in male offspring. To our knowledge this has never been studied in humans.METHOD: In the Odense Child Cohort pregnant women residing in Odense municipality, Denmark, were recruited at gestational age 8-16 weeks between 2010 and 2012. Of the eligible 2421 mother-child pairs, 812 mother-son pairs were included. Questionnaire data on medicine use were collected in first and third trimester and physical examination at age 3 month was performed. Ano-scrotal distance; measured from the centre of anus to the posterior base of scrotum (AGDas). Ano-cephalad distance; measured from the centre of anus to the cephalad insertion of the penis (AGDap) and penile width; measured at the base of the penis.RESULTS: Eighty seven women had used antifungal medicine during pregnancy. Maternal use of oral fluconazole (n = 4) was associated with a 6.4 mm shorter AGDas (95% CI: -11.9;-0.9) in the male offspring. Use of antifungal vaginal tablets (n = 21), was associated with a non-significantly shorter AGDas (-1.9 mm; 95% CI: -4.3; 0.5) whereas exposure to vaginal cream (n = 23) was not associated to AGDas. Use of antifungal medicine in the window of genital development between 8 and 14 weeks of gestation was associated with a larger reduction in AGDas than exposure outside this window. Antifungal medicine intake was not associated with AGDap and penil width.CONCLUSION: Our preliminary findings prompted us to hypothesize that maternal use of conazole antifungal medication during pregnancy may affect the masculinization of male offspring. If confirmed, pregnant women should be advised to use antifungal medicine with caution.",
keywords = "Adult, Androgen Antagonists/adverse effects, Antifungal Agents/adverse effects, Denmark, Female, Fluconazole/adverse effects, Genitalia, Male/anatomy & histology, Humans, Infant, Male, Pregnancy, Prenatal Exposure Delayed Effects",
author = "Mogensen, {Djamilla Madelung} and Pihl, {Maria Bergkvist} and Skakkeb{\ae}k, {Niels E} and Andersen, {Helle Raun} and Anders Juul and Kyhl, {Henriette Boye} and Shanna Swan and Kristensen, {David M{\o}bjerg} and Andersen, {Marianne Skovager} and Lind, {Dorte Vesterholm} and Jensen, {Tina Kold}",
year = "2017",
doi = "10.1186/s12940-017-0263-z",
language = "English",
volume = "16",
pages = "68",
journal = "Environmental Health: A Global Access Science Source",
issn = "1476-069X",
publisher = "BioMed Central Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - Prenatal exposure to antifungal medication may change anogenital distance in male offspring

T2 - a preliminary study

AU - Mogensen, Djamilla Madelung

AU - Pihl, Maria Bergkvist

AU - Skakkebæk, Niels E

AU - Andersen, Helle Raun

AU - Juul, Anders

AU - Kyhl, Henriette Boye

AU - Swan, Shanna

AU - Kristensen, David Møbjerg

AU - Andersen, Marianne Skovager

AU - Lind, Dorte Vesterholm

AU - Jensen, Tina Kold

PY - 2017

Y1 - 2017

N2 - BACKGROUND: Vaginal candidiasis is frequent among pregnant women and it is treated with anti-fungal medication (conazoles). Conazoles have anti-androgenic properties and prenatal exposure in rodents is associated with a shorter (less masculine) anogenital distance (AGD) in male offspring. To our knowledge this has never been studied in humans.METHOD: In the Odense Child Cohort pregnant women residing in Odense municipality, Denmark, were recruited at gestational age 8-16 weeks between 2010 and 2012. Of the eligible 2421 mother-child pairs, 812 mother-son pairs were included. Questionnaire data on medicine use were collected in first and third trimester and physical examination at age 3 month was performed. Ano-scrotal distance; measured from the centre of anus to the posterior base of scrotum (AGDas). Ano-cephalad distance; measured from the centre of anus to the cephalad insertion of the penis (AGDap) and penile width; measured at the base of the penis.RESULTS: Eighty seven women had used antifungal medicine during pregnancy. Maternal use of oral fluconazole (n = 4) was associated with a 6.4 mm shorter AGDas (95% CI: -11.9;-0.9) in the male offspring. Use of antifungal vaginal tablets (n = 21), was associated with a non-significantly shorter AGDas (-1.9 mm; 95% CI: -4.3; 0.5) whereas exposure to vaginal cream (n = 23) was not associated to AGDas. Use of antifungal medicine in the window of genital development between 8 and 14 weeks of gestation was associated with a larger reduction in AGDas than exposure outside this window. Antifungal medicine intake was not associated with AGDap and penil width.CONCLUSION: Our preliminary findings prompted us to hypothesize that maternal use of conazole antifungal medication during pregnancy may affect the masculinization of male offspring. If confirmed, pregnant women should be advised to use antifungal medicine with caution.

AB - BACKGROUND: Vaginal candidiasis is frequent among pregnant women and it is treated with anti-fungal medication (conazoles). Conazoles have anti-androgenic properties and prenatal exposure in rodents is associated with a shorter (less masculine) anogenital distance (AGD) in male offspring. To our knowledge this has never been studied in humans.METHOD: In the Odense Child Cohort pregnant women residing in Odense municipality, Denmark, were recruited at gestational age 8-16 weeks between 2010 and 2012. Of the eligible 2421 mother-child pairs, 812 mother-son pairs were included. Questionnaire data on medicine use were collected in first and third trimester and physical examination at age 3 month was performed. Ano-scrotal distance; measured from the centre of anus to the posterior base of scrotum (AGDas). Ano-cephalad distance; measured from the centre of anus to the cephalad insertion of the penis (AGDap) and penile width; measured at the base of the penis.RESULTS: Eighty seven women had used antifungal medicine during pregnancy. Maternal use of oral fluconazole (n = 4) was associated with a 6.4 mm shorter AGDas (95% CI: -11.9;-0.9) in the male offspring. Use of antifungal vaginal tablets (n = 21), was associated with a non-significantly shorter AGDas (-1.9 mm; 95% CI: -4.3; 0.5) whereas exposure to vaginal cream (n = 23) was not associated to AGDas. Use of antifungal medicine in the window of genital development between 8 and 14 weeks of gestation was associated with a larger reduction in AGDas than exposure outside this window. Antifungal medicine intake was not associated with AGDap and penil width.CONCLUSION: Our preliminary findings prompted us to hypothesize that maternal use of conazole antifungal medication during pregnancy may affect the masculinization of male offspring. If confirmed, pregnant women should be advised to use antifungal medicine with caution.

KW - Adult

KW - Androgen Antagonists/adverse effects

KW - Antifungal Agents/adverse effects

KW - Denmark

KW - Female

KW - Fluconazole/adverse effects

KW - Genitalia, Male/anatomy & histology

KW - Humans

KW - Infant

KW - Male

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects

U2 - 10.1186/s12940-017-0263-z

DO - 10.1186/s12940-017-0263-z

M3 - Journal article

C2 - 28637461

VL - 16

SP - 68

JO - Environmental Health: A Global Access Science Source

JF - Environmental Health: A Global Access Science Source

SN - 1476-069X

IS - 1

ER -

ID: 55228985