It is no secret that gender bias is prevalent in biomedical and population health research. Not only is basic science research biased against females, but so are clinical trials. The exclusion of non-white, non-male, and non-cis-gender research subjects in clinical trials is justified by the need to “minimize” extraneous variables. This has led to the systematic exclusion of women, non-cis-gender, and Black, Indigenous, and People of Color (BIPOC) individuals in research and created gaps in managing the health of individuals of different races and ethnicities across both the gender and sex spectra.
A person’s state of health is a product of an interaction between their genetic composition and their collective lifelong environmental exposures. Since men and women are largely genetically similar except for differences due to their sex chromosomes, environmental exposures are the main determinants of sex-specific health outcomes. Environmental exposure is determined by cultural norms, which are in turn dictated by heterosexism, classism, misogyny, patriarchy, and racism. Therefore, biological sex and gender identity may influence the types and patterns of environmental exposures that an individual experiences.
A recent review by Dr. Meghan L. Bucher and colleagues, from the Department of Environmental Health Sciences, presents the exposome as a tool to analyze both environmental exposures and the associated biological effects of those exposures to understand how the intersection of environmental health and biological sex and gender identity impact health.
Exposome, a word introduced 15 years ago, is a new field that aims to provide an environmental complement to the genome. While there have been substantial advances in genomics over the past decade, the environment remains mysterious from a scientific standpoint because it does not lend itself to a systematic evaluation of its constituent components. Historically, we have not been able to comprehensively analyze the environment in a way such that it fits into the biomedical framework. That is what the exposomics sets out to deliver. Further, it also aims to provide an analysis of how our biology responds to those environmental exposures. In conventional analyses, only a few exposures or markers are targeted, whereas, exposomics characterizes all exposures in an untargeted and comprehensive manner. For example, exposomics use high-resolution mass spectrometry (HRMS) technologies that facilitate high-throughput detection of compounds or chemical patterns from complex and dynamic exposures.
Exposure patterns may vary significantly depending on biological sex and gender identity. Further, exposures may exert sex-specific effects by interacting with biological factors such as sex hormones. The ability to define and characterize one’s exposome based on gender identity and biological sex would provide critical insight into factors influencing an individual’s health.
An example of how biological sex determines exposure patterns can be seen in how specific occupations and household responsibilities are historically segregated – men tend to outnumber women in professions such as law enforcement, the military, and politics; women on the other hand tend to do more household chores than men. This can potentially cause different environmental exposures in men and women. Furthermore, biological sex can influence the use of personal care products, such as menstrual and intimate care products and hormonal contraceptives.
Gender identity can likewise influence the use of personal care products including cosmetics and other beauty products. This is partly because such products are marketed mainly to women, female-identifying, and feminine-presenting consumers, who are the primary targets of unrealistic beauty standards. Studies show that women use approximately twice as many personal care products each day compared with men, which results in higher exposure to chemicals and toxic substances, including exposure to carcinogens, nanoparticles, and metals.
Since the environment itself as well as the environmental exposure are constantly changing, assessing the environmental factors at a specific point in time provides limited insight into collective exposures or exposures during key developmental periods. In contrast, exposome-wide characterization, which features the use of HRMS-based assays, can profile a variety of biospecimens in an untargeted and unbiased way to simultaneously identify both exogenous factors and endogenous responses to those exposures.
Exposomics as a field is still in its early stages. However, there have been some initial studies that looked at the differences in the metabolomic profiles of men and women, as defined by biological sex, in healthy and disease states. These studies have revealed baseline differences based on biological sex such as creatinine content (a chemical waste product produced by our body), steroid hormones, and branched-chain amino acids.
Going forward, new frameworks, as summarized in Figure 1, can systematically incorporate exposomic characterizations in health outcomes and interventions. For example, new digital databases (that include e.g., environmental data, chemicals, and toxicokinetics), biobanking (e.g., BioBank procedures), analytical platforms such as HRMS, and computing power (e.g., cloud computing services) need to be constructed in order to characterize the exposome on multiple levels depending on the research questions asked. Once this has been achieved, questions can focus on how the differences in exposome profiles identified lead to altered health outcomes, and further incorporate these findings into basic science research, clinical trial design, and data science approaches.
Such a parallel exposomic platform may initially seem intractable. However, the National Institutes of Health (NIH) recently launched a new initiative titled “All of Us”, aimed at gathering data from more than one million US citizens. This database could be an excellent resource of data from which to build a more complete understanding of the exposome.
An intersectional approach – sex- and gender-specific environmental exposure and its evaluation for impact on health – with a rigorous effort to not only include but center women, sexual and gender minorities, and BIPOC individuals in health research will help to remedy our current dearth of understanding regarding sex- and gender-specific health outcomes. The findings can be translated into educational efforts, among stakeholders, scientists, and the public, to increase awareness of the role of the environment in sex- and gender-specific health. This can in turn inform policymaking regarding the regulation of environmental factors and exposures. Ultimately, such research will help to manage individual health risk assessment and precision medicine, where individual behaviors may be geared to improve health.
Reviewers: Trang Nguyen, Maaike Schilperoort