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
SN - 1476-069X
VL - 16
SP - 68
JO - Environmental Health: A Global Access Science Source
JF - Environmental Health: A Global Access Science Source
IS - 1
ER -