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

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.

Effects of nonsteroidal anti‐inflammatory drug (NSAID) use upon male gonadal function: A national, population‐based study

“…Third, Kristensen et al examined ibuprofen exposure specifically, whereas the current study included a wide variety of NSAIDs including salicylates and others. Thus, the short‐term association with compensated hypogonadism could be ibuprofen‐specific through a direct anti‐androgenic action of the drug, as suggested by the authors (Kristensen et al, ).…”

“…Fourth, as mentioned above, the use of AMH in lieu of LH for determination of compensated hypogonadism could mischaracterise a subset of patients with discrepant LH and AMH levels. While this definition was necessitated by the data, prior evidence from Kristensen et al suggests that AMH is reliably suppressed in the compensated hypogonadal state and, therefore, should be considered an accurate marker thereof (Kristensen et al, ). Fifth, NSAIDs are used for a variety of conditions and scenarios, some of which could serve as unmeasured confounders in the present study.…”

“…Testosterone ( should be considered an accurate marker thereof (Kristensen et al, 2018). Fifth, NSAIDs are used for a variety of conditions and scenarios, some of which could serve as unmeasured confounders in the present study.…”

“…For this reason, AMH has been used as a valuable marker for assessment of gonadal function (Matuszczak et al, 2013). Kristensen et al, (2018) reported that while AMH levels were uncoupled from gonadotropins, AMH was reliably suppressed in the setting of compensated hypogonadism, thereby supporting the use of AMH as a surrogate marker of compensated hypogonadism.…”

Increasing ibuprofen degradation in constructed wetlands by bioaugmentation with gravel containing biofilms of an ibuprofen‐degrading Sphingobium yanoikuyae

“…Investigations into ibuprofen environmental impacts have found induced changes on growth and predominance of algae and duckweed, the timing of spawning by medaka (Japanese rice fish Oryzias latipes) , riverine biofilm communities at relevant concentrations, as well as changes in microbial diversity in aquatic mesocosms . Ibuprofen was also reported to alter human testicular physiology, altering the endocrine system via selective transcriptional repression, thereby inducing compensated hypogonadism .…”