Abstract
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.
Highlights
Adverse drug reactions are common and thought to be the fourth leading cause of death.[1]
A 2018 study performed in the Netherlands evaluating adverse drug reactions (ADR) related to the use of selective serotonin reuptake inhibitors (SSRIs) from 2003 to 2016 found that among the 6791 ADR reports, 68% involved women; the percentage of severe reactions was higher among men (31.6% vs 22.9%)
There are data supporting sex differences in ADRs, there are few systematic analyses of these adverse events by drug class that take into account stages of life, and hormonal status
Summary
Adverse drug reactions are common and thought to be the fourth leading cause of death.[1]. Few studies have addressed potential hormone‐ drug interactions except for managing trans patients with sickle cell disease,[68] and treatments for HIV.[69] both trans men and trans women report reductions in anxiety, depression and per‐ ceived stress when treated with hormone therapy,[61] individuals using pharmaceutical treatments for other conditions prior to ini‐ tiation of the steroid hormones may require adjustment for those medications This adjustment may be due to the drug‐hormone interactions involving metabolic pathways discussed previously or due to interactions of steroids hormones with molecular targets for those drugs.[70] Hormone‐drug interactions for other medications, statins, for example, are unknown in the trans population given the age of the individuals when therapy was initiated and the impact of the hormones on metabolic factors that influence development of atherosclerosis with aging in cis men.
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