Sarah Munk Andreasen , Anna-Patricia Iversen , Lars Christian Lund , Margit Bistrup Fischer , Anna-Maria Andersson , Naja Kamuk Rauer , Gylli Mola , Anders Juul , Casper P. Hagen , Tina Kold Jensen
{"title":"母亲应用热带抗真菌药物可降低青春期前期的类固醇激素水平,缩短3个月至9岁的后代的肛门生殖器距离:欧登塞儿童队列","authors":"Sarah Munk Andreasen , Anna-Patricia Iversen , Lars Christian Lund , Margit Bistrup Fischer , Anna-Maria Andersson , Naja Kamuk Rauer , Gylli Mola , Anders Juul , Casper P. Hagen , Tina Kold Jensen","doi":"10.1016/j.reprotox.2025.109007","DOIUrl":null,"url":null,"abstract":"<div><div>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 <em>minipuberty</em> 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.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109007"},"PeriodicalIF":2.8000,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"Sarah Munk Andreasen , Anna-Patricia Iversen , Lars Christian Lund , Margit Bistrup Fischer , Anna-Maria Andersson , Naja Kamuk Rauer , Gylli Mola , Anders Juul , Casper P. Hagen , Tina Kold Jensen\",\"doi\":\"10.1016/j.reprotox.2025.109007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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 <em>minipuberty</em> 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.</div></div>\",\"PeriodicalId\":21137,\"journal\":{\"name\":\"Reproductive toxicology\",\"volume\":\"137 \",\"pages\":\"Article 109007\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-07-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Reproductive toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0890623825001789\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"REPRODUCTIVE BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive toxicology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0890623825001789","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
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
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.
期刊介绍:
Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine.
All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.