{ "abstract": "Study question\n\nIs prenatal exposure to paracetamol associated with testicular function in male offspring?Summary answer\n\nPrenatal paracetamol exposure was associated with smaller testicular volume in infant boys.What is known already\n\nParacetamol (also known as acetaminophen) is available over the counter and is frequently used by pregnant women. Animal studies and secondary analyses of mother-child cohorts suggest paracetamol can adversely affect testicular development. To our knowledge, this is the first cohort study primarily designed to test the association between prenatal paracetamol exposure and postnatal testicular function.Study design size duration\n\nProspective, observational pregnancy and birth cohort at a university hospital (2020-2022). Healthy, singleton pregnant women (n = 685) were enrolled during the first trimester, and 589 (287 boys) infants completed follow-up examination at 3 months of age.Participants/materials setting methods\n\nData on maternal paracetamol use (yes/no and dose) were collected prospectively every 2 weeks throughout pregnancy. Based on the timing of fetal masculinization, participants were classified as exposed at any time during fetal life (n = 137), early exposure (gestational week (GW) ≤ 15; n = 81), late exposure (GW >15; n = 118), or exposed during both early and late fetal life (n = 62). Unexposed boys served as controls (n = 150).The boys were examined at infancy (i.e. minipuberty at mean age 3.1 months ±0.3 SD). Predefined primary outcomes: anogenital distance (AGD), testicular volume, and circulating levels of testosterone.Main results and the role of chance\n\nAcross exposure windows, prenatal paracetamol exposure was consistently associated with smaller testicular volume at 3 months of age. Effect estimates were largest in boys exposed at early as well as late fetal life; dose of paracetamol, median (interquartile range (IQR)) 8.5 g (4.0-16.6), testicular volume (β) -34.1 mm³, 95% CI -65.5 to -2.7, P = 0.033.Limitations reasons for caution\n\nResidual confounding by indication cannot be excluded. The generalizability of the study may be affected by the homogeneity of the Copenhagen Analgesic Study (COPANA) cohort. Longitudinal follow-up is necessary for evaluation of reproductive health in adulthood.Wider implications of the findings\n\nIn this prospective human cohort study, prenatal paracetamol exposure was associated with reduced testicular volume during minipuberty, a transient period of postnatal activation of the hypothalamic-pituitary-gonadal axis that is considered a critical window for assessing future reproductive function.Funding\n\nRigshospitalet Research Council supports this work under grants (E-22778-02) and (E-22717-21). The research was furthermore funded by Læge Sofus Carl Emil Friis og hustru Doris Friis'Legat (F-23936-01), Aase og Ejnar Danielsens Foundation (20-10-0367), Helsefonden (20-B-0388), Axel Muusfeldt fond (2020-0385), and The Danish Centre for Endocrine Disrupting Substances (CeHoS) (2022-23219). The publication was completed as part of the MERLON project under grant agreement No. 101137411. The MERLON project is funded by the European Union. Views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency (HADEA). Neither the European Union nor HADEA can be held responsible for them.Disclosures\n\nD.M.K. has received speaker fees from Merck. A.J. has received speaker fees from Ipsen, Novo Nordisk, and Sandoz. A.J. is Head of Department at a department that has received unrestricted research grants from Novo Nordisk and Lundbeck. All other authors declare no conflicts of interest.Trial registration number\n\nThe Copenhagen Analgesic Study (COPANA) (ClinicalTrials.gov NCT04369222).", "abstract_shown": true, "affiliations": [ "Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.", "International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.", "Center of Fetal Medicine and Pregnancy, Department of Obstetrics, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.", "Department of Gynaecology, Fertility and Obstetrics, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.", "Research Unit of Gynaecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.", "Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.", "Department of Science and Environment, Roskilde University, Roskilde, Denmark." ], "article_type": "research article", "arxiv": null, "author_total": 11, "authors": [ { "affs": [ 0, 1 ], "name": "Gylli Mola", "orcid": "0000-0002-9853-999X" }, { "affs": [ 0, 1 ], "name": "Margit Bistrup Fischer", "orcid": "0000-0002-7999-548X" }, { "affs": [ 0, 1 ], "name": "Hanne Frederiksen" }, { "affs": [ 0 ], "name": "Jørgen Holm Petersen" }, { "affs": [ 2 ], "name": "Lone Scheel" }, { "affs": [ 2 ], "name": "Katrine Bak Wraae" }, { "affs": [ 3, 4 ], "name": "Ane Lilleøre Rom", "orcid": "0000-0003-2474-2677" }, { "affs": [ 3, 5 ], "name": "Hanne Kristine Hegaard" }, { "affs": [ 0, 6 ], "name": "David Møbjerg Kristensen", "orcid": "0000-0003-0657-1632" }, { "affs": [ 0, 1, 5 ], "name": "Anders Juul", "orcid": "0000-0002-0534-4350" }, { "affs": [ 0, 1, 5 ], "name": "Casper P Hagen" } ], "bibtex": "https://research.draconitic.com/paper/bfbq64wqht7ez.bib", "cited_by": 0, "doi": "10.1093/hropen/hoag089", "fulltext_url": "https://europepmc.org/articles/PMC13716481", "id": "bfbq64wqht7ez", "issns": [ "2399-3529" ], "landing_url": "https://europepmc.org/article/MED/42953900", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "AcademicSubjects/MED00905" ], [ "heading", "Editor's Choice" ], [ "heading", "Original Article" ], [ "openalex", "2307|Effects and risks of endocrine disrupting chemicals" ] ], "openalex": "W7220725326", "pdf_url": "https://europepmc.org/articles/PMC13716481?pdf=render", "pmcid": "PMC13716481", "pmid": "42953900", "published": "2026-10-06", "publisher": "Oxford University Press", "ris": "https://research.draconitic.com/paper/bfbq64wqht7ez.ris", "sources": [ { "first_seen": "2026-10-31T00:20:41Z", "native_id": "MED:42953900", "source": "europepmc", "url": "https://europepmc.org/article/MED/42953900" }, { "first_seen": "2026-11-01T12:23:25Z", "native_id": "PMC13716481", "source": "pmc", "url": "https://doi.org/10.1093/hropen/hoag089" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2307|Effects and risks of endocrine disrupting chemicals", "subfield": "pharmacology-toxicology" } ], "title": "Prenatal exposure to paracetamol is associated with smaller testicular volume: a COPANA cohort study of 287 healthy infant boys.", "title_text": "Prenatal exposure to paracetamol is associated with smaller testicular volume: a COPANA cohort study of 287 healthy infant boys.", "type": "peer-reviewed", "updated_at": "2026-11-01T12:23:25Z", "url": "https://research.draconitic.com/paper/bfbq64wqht7ez", "venue": "Human reproduction open", "versions": [] }