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Individualized medicine: Sex, hormones, genetics, and adverse drug reactions

Clinically relevant adverse drug reactions differ between men and women. The underlying physiological and pharmacological processes contributing to these differences are infrequently studied or reported. As gene expression, cellular regulatory pathways, and integrated physiological functions differ...

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Detalles Bibliográficos
Autores principales: Moyer, Ann M., Matey, Eric T., Miller, Virginia M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897337/
https://www.ncbi.nlm.nih.gov/pubmed/31844524
http://dx.doi.org/10.1002/prp2.541
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author Moyer, Ann M.
Matey, Eric T.
Miller, Virginia M.
author_facet Moyer, Ann M.
Matey, Eric T.
Miller, Virginia M.
author_sort Moyer, Ann M.
collection PubMed
description Clinically relevant adverse drug reactions differ between men and women. The underlying physiological and pharmacological processes contributing to these differences are infrequently studied or reported. As gene expression, cellular regulatory pathways, and integrated physiological functions differ between females and males, aggregating data from combined groups of men and women obscures the ability to detect these differences. This paper summarizes how genetic sex, that is, the presence of sex chromosomes XY for male or XX for female, and the influence of sex hormones affect transporters, receptors, and enzymes involved in drug metabolism. Changing levels of sex steroids throughout life, including increases at puberty, changes with pregnancy, and decreases with age, may directly and indirectly affect drug absorption, distribution, metabolism, and elimination. The direct and indirect effects of sex steroids in the form of exogenous hormones such as those used in hormonal contraceptives, menopausal hormone treatments, transgender therapy, and over‐the‐counter performance enhancing drugs may interfere with metabolism of other pharmaceuticals, and these interactions may vary by dose, formulation, and mode of delivery (oral, injection, or transdermal) of the steroid hormones. Few drugs have sex‐specific labeling or dosing recommendations. Furthermore, there is limited literature evaluating how the circulating levels of sex steroids impact drug efficacy or adverse reactions. Such research is needed in order to improve the understanding of the impact of sex hormones on pharmacological therapies, particularly as medicine moves toward individualizing treatments.
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spelling pubmed-68973372019-12-16 Individualized medicine: Sex, hormones, genetics, and adverse drug reactions Moyer, Ann M. Matey, Eric T. Miller, Virginia M. Pharmacol Res Perspect Original Articles Clinically relevant adverse drug reactions differ between men and women. The underlying physiological and pharmacological processes contributing to these differences are infrequently studied or reported. As gene expression, cellular regulatory pathways, and integrated physiological functions differ between females and males, aggregating data from combined groups of men and women obscures the ability to detect these differences. This paper summarizes how genetic sex, that is, the presence of sex chromosomes XY for male or XX for female, and the influence of sex hormones affect transporters, receptors, and enzymes involved in drug metabolism. Changing levels of sex steroids throughout life, including increases at puberty, changes with pregnancy, and decreases with age, may directly and indirectly affect drug absorption, distribution, metabolism, and elimination. The direct and indirect effects of sex steroids in the form of exogenous hormones such as those used in hormonal contraceptives, menopausal hormone treatments, transgender therapy, and over‐the‐counter performance enhancing drugs may interfere with metabolism of other pharmaceuticals, and these interactions may vary by dose, formulation, and mode of delivery (oral, injection, or transdermal) of the steroid hormones. Few drugs have sex‐specific labeling or dosing recommendations. Furthermore, there is limited literature evaluating how the circulating levels of sex steroids impact drug efficacy or adverse reactions. Such research is needed in order to improve the understanding of the impact of sex hormones on pharmacological therapies, particularly as medicine moves toward individualizing treatments. John Wiley and Sons Inc. 2019-12-06 /pmc/articles/PMC6897337/ /pubmed/31844524 http://dx.doi.org/10.1002/prp2.541 Text en © 2019 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Moyer, Ann M.
Matey, Eric T.
Miller, Virginia M.
Individualized medicine: Sex, hormones, genetics, and adverse drug reactions
title Individualized medicine: Sex, hormones, genetics, and adverse drug reactions
title_full Individualized medicine: Sex, hormones, genetics, and adverse drug reactions
title_fullStr Individualized medicine: Sex, hormones, genetics, and adverse drug reactions
title_full_unstemmed Individualized medicine: Sex, hormones, genetics, and adverse drug reactions
title_short Individualized medicine: Sex, hormones, genetics, and adverse drug reactions
title_sort individualized medicine: sex, hormones, genetics, and adverse drug reactions
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897337/
https://www.ncbi.nlm.nih.gov/pubmed/31844524
http://dx.doi.org/10.1002/prp2.541
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