Maternal application of tropical antifungal medication is associated with reduced steroid hormone levels during minipuberty and shorter anogenital distance in offspring from 3 months to 9 years of age: Odense Child Cohort

Abstract

Vaginal candidiasis affects about 20 % of pregnant women and is usually treated with over-the-counter topical antifungal medication (azoles). Vaginal or transdermal application of azoles are absorbed and detectable in circulation. Azoles inhibit CYP51, which is crucial for the integrity of fungal cellular membranes. However, cell cultures have shown that azoles also affect steroidogenesis. This study investigated maternal antifungal application during pregnancy and the association with reproductive hormones during minipuberty and anogenital distance (AGD) the in the offspring from infancy to 9 years of age. In the Odense Child Cohort (2010–2012), women completed questionnaires about antifungal application during pregnancy. Serum concentrations of luteinising hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estrone (E1), estradiol (E2), Δ4-androstenedione (adione), 17α-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone-sulphate (DHEAS) were analysed in 454 infants at 3 months. AGD was assessed at 3, 18 months and 3, 5, 7 and 9 years of age, with 1792 measurements. Topical antifungal application during pregnancy was reported by 35 women. In boys, maternal application before GW 19 was associated with shorter AGD as well as lower adrenal hormone levels. In girls, application before GW 19 was associated with longer AGD and lower reproductive and adrenal hormone levels, while application after GW 19 was associated with shorter AGD, while hormone levels did not differ. Given the small number of cases, the findings should be interpreted with caution. The widespread use of over-the-counter antifungals appears to affect AGD and hormone production in offspring, which is concerning and may have long-term consequences for reproductive health.