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Analgesic use — prevalence, biomonitoring and endocrine and reproductive effects

Key Points

  • Mild analgesics (hereafter, analgesics) consisting of paracetamol and NSAIDs are among the most used pharmaceutical drugs worldwide as well as the most released into the environment

  • Epidemiological data indicate a connection between maternal intake of analgesics and congenital reproductive abnormalities

  • Analgesics can have endocrine-disruptive actions in animals and humans of both sexes, from fetal life to adulthood

  • Medical and public awareness (especially that of pregnant women) must be increased about the potential hazards of analgesic use

Abstract

Paracetamol and NSAIDs, in particular acetylsalicylic acid (aspirin) and ibuprofen, are among the most used and environmentally released pharmaceutical drugs. The differences in international trends in the sale and consumption of mild analgesics reflect differences in marketing, governmental policies, habits, accessibility, disease patterns and the age distribution of each population. Biomonitoring indicates ubiquitous and high human exposure to paracetamol and to salicylic acid, which is the main metabolite of acetylsalicylic acid. Furthermore, evidence suggests that analgesics can have endocrine disruptive properties capable of altering animal and human reproductive function from fetal life to adulthood in both sexes. Medical and public awareness about these health concerns should be increased, particularly among pregnant women.

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Figure 1: Temporal changes in the sales of acetylsalicylic acid, paracetamol and ibuprofen.
Figure 2: Temporal changes in the consumption of mild analgesics during pregnancy.
Figure 3: Consumption of mild analgesics across the three trimesters of pregnancy.
Figure 4: Simplified metabolism of analgesics.

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Acknowledgements

The authors' research is funded by The Danish Council for Independent Research (Medical Sciences) [D.M.K.], the Fondation pour la Recherche Médicale [P.G.], Inserm (Institut national de la santé et de la recherche médicale) [B.J., S.M.-G.], Rennes 1 University [L.L.], EHESP–School of Public Health [B.J., T.S.] and ANSM (Agence Nationale de la Sécurité du Médicament; grants N° AAP-2012-037 and N° HAP-2014-073) [B.J.]. We also thank T. Renberg from the Swedish Health Agency and T. Partio from the Finnish social security institution KELA for providing us with pharmaceutical sales data.

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D.M.K., S.M.-G., P.G., L.L., T.S., and B.J. researched data for the article. D.M.K., S.M.-G., K.M.M. and B.J. made substantial contributions to discussions of the content. D.M.K., S.M.-G. and B.J. wrote the article. D.M.K., S.M.-G., L.L., K.M.M. and B.J. reviewed and/or edited the article before submission.

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Correspondence to David M. Kristensen or Bernard Jégou.

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The history of consumption of analgesics by pregnant women. (PDF 305 kb)

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Worldwide consumption of mild analgesics during pregnancy. (PDF 221 kb)

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Kristensen, D., Mazaud-Guittot, S., Gaudriault, P. et al. Analgesic use — prevalence, biomonitoring and endocrine and reproductive effects. Nat Rev Endocrinol 12, 381–393 (2016). https://doi.org/10.1038/nrendo.2016.55

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