TY - JOUR
T1 - Individualized medicine
T2 - Sex, hormones, genetics, and adverse drug reactions
AU - Moyer, Ann M.
AU - Matey, Eric T.
AU - Miller, Virginia M.
N1 - Publisher Copyright:
© 2019 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - estrogen
KW - men
KW - testosterone
KW - transgender
KW - women
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U2 - 10.1002/prp2.541
DO - 10.1002/prp2.541
M3 - Review article
C2 - 31844524
AN - SCOPUS:85076714372
SN - 2052-1707
VL - 7
SP - e00541
JO - Pharmacology research & perspectives
JF - Pharmacology research & perspectives
IS - 6
ER -