The Inclusion of Sex and Gender Beyond the Binary in Toxicology

Abstract

Assigned sex is the label given at birth by medical professionals based on an individual's chromosomes, hormone levels, sex organs, and secondary sex characteristics. As a note, the term "biologic sex" is understood by many to be an outdated term, due to its longstanding history of being used to invalidate the authenticity of trans identities. Although sex is typically misconceptualized as a binary of male (XY) or female (XX), many other chromosomal arrangements, inherent variations in gene expression patterns, and hormone levels exist. Intersex categorizations include variations in chromosomes present, external genitalia, gonads (testes or ovaries), hormone production, hormone responsiveness, and internal reproductive organs. Medical classification of intersex individuals is not always done at birth, as many intersex traits do not become apparent until puberty or later in life. Currently, there are at least 40 known variations that fall into intersex classifications (Carpenter, 2018). Notably, complex biologic variations can occur in everyone, and sex may best be viewed as a spectrum comprised of many traits. Gender is widely understood to be distinguished from sex and is an experienced aspect of self and a social construct of norms, behaviors, and roles that varies between societies and over time.

Risk assessment of transgender people: implementation of a demasculinizing–feminizing rodent model including the evaluation of thyroid homeostasis

“…HT is a long-term treatment, which lasts for the entire life of the individual, so it is essential to study all possible side effects [ 6 , 7 ]. In addition, like general population, TG people are exposed to environmental contaminants; [ 6 , 8 ] indeed, for TG people, HT might represent an additional risk factor and the implementation of a specific animal model to address the hazard identification is of primary importance [ 6 ].…”

“…T serum level is measured to verify the achievement of the corresponding cisgender levels and specific functional and tissue biomarkers have been identified to characterize the model, in particular: sperm count, E2 serum levels, histopathological analysis of testis and liver, and the gene expression of sex-specific liver cytochrome P450 (CYP450) isoforms identified as biomarkers of liver demasculinization after two weeks of HT in the dMF rat model [ 10 ]. Since in TG individuals undergoing HT the endocrine system is overstimulated by the therapy, they may represent a sub-population more vulnerable and susceptible [ 6 – 8 ] than the general population to the effects of endocrine disrupters (EDs). EDs are defined as "an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action".…”

Exposomics as a tool to investigate differences in health and disease by sex and gender

“…For instance, there have been significant efforts to be inclusive of SGMs in toxicology research and medicine, with researchers further outlining how animal models can be used to address the health of individuals participating in gender affirming hormone therapies. 70 , 71 Additionally, in the realm of environmental justice, focus is being dedicated to the disparity in environmental exposures for marginalized populations such as LGBTQIA+ individuals. 72 Concepts such as the public health exposome can guide these efforts to translate the findings from exposomic research into tangible changes.…”

Sex and Gender in Orthopaedic Research

“…For some people, gender can be fluid, while the assumption is that sex is strictly binary. However, sex is not necessarily binary for all individuals and may be thought of as a spectrum, as there can be chromosomal arrangements other than XX or XYor inherent variations in gene-expression patterns and sex hormone levels 4 . There is also emerging evidence of the role of epigenetics in translating environmental exposures to how genes function, often blurring the lines in some areas between the relative roles of gender and sex.…”