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Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):E715-E724. doi: 10.1073/pnas.1715035115. Epub 2018 Jan 8.

Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism.

Author information

1
Danish Headache Center, Department of Neurology, Rigshospitalet, University of Copenhagen, 1165 Copenhagen, Denmark.
2
Université de Rennes I, Inserm, EHESP-School of Public Health, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, F-35000 Rennes, France.
3
Novo Nordisk Foundation Center for Protein Research Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3A, 2200 Copenhagen, Denmark.
4
Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital, 2400 Copenhagen NV, Denmark.
5
Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark.
6
DTU Bio and Health Informatics, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
7
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark.
8
L'Université Nantes Angers Le Mans (LUNAM), Oniris, UMR 1329 INRA Laboratoire d'Etude des Résidus et Contaminants dans les Aliments (LABERCA), F-44307 Nantes, France.
9
Unité de coordination hospitalière des prélèvements d'organes et de tissus, Centre Hospitalier Universitaire de Rennes, 35000 Rennes, France.
10
Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark.
11
Department of Environmental Medicine, University of Southern Denmark, 5000 Odense, Denmark.
12
Department of Biology, Faculty of Science, University of Copenhagen, 2100 Copenhagen, Denmark.
13
Institute of Metagenomics, BGI-Shenzhen, Shenzhen 518083, China.
14
Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, DK-2200 Copenhagen, Denmark
15
EDMaRC (International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health), Rigshospitalet, University of Copenhagen, DK-2200 Copenhagen, Denmark.

Abstract

Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named "compensated hypogonadism," a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism.

KEYWORDS:

endocrine disruption; endocrinology; hypogonadism; ibuprofen; reproduction

PMID:
29311296
PMCID:
PMC5789927
DOI:
10.1073/pnas.1715035115
[Indexed for MEDLINE]
Free PMC Article

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