TY - JOUR
T1 - Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism
AU - Kristensen, David Møbjerg
AU - Desdoits-Lethimonier, Christèle
AU - Mackey, Abigail L
AU - Dalgaard, Marlene Danner
AU - De Masi, Federico
AU - Munkbøl, Cecilie Hurup
AU - Styrishave, Bjarne
AU - Antignac, Jean-Philippe
AU - Le Bizec, Bruno
AU - Platel, Christian
AU - Hay-Schmidt, Anders
AU - Jensen, Tina Kold
AU - Lesné, Laurianne
AU - Mazaud-Guittot, Séverine
AU - Kristiansen, Karsten
AU - Brunak, Søren
AU - Kjær, Michael
AU - Juul, Anders Christian
AU - Jégou, Bernard
N1 - This open access article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND).
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Endocrine disruption
KW - Endocrinology
KW - Hypogonadism
KW - Ibuprofen
KW - Reproduction
U2 - 10.1073/pnas.1715035115
DO - 10.1073/pnas.1715035115
M3 - Journal article
C2 - 29311296
SN - 0027-8424
VL - 115
SP - E715-E724
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 17
M1 - E4143
ER -