Abstract
Diversity is a hallmark of successful species. It promotes evolutionary flexibility, adaptation and survivalism. The melting pot of gene mingling, during human reproduction provides our species with an almost infinite range of variations and combinations that are expressed slightly differently in each person, making each of us unique. Genetic makeup can be expressed in physical traits, which are then modified by our higher thinking, interpretations and emotional and mental constructs. Therefore, aspects of personality and physicality, although grounded in the same genetic code, can take different visible forms, in the same way as there are many variation of what a shirt might look like.
Accepting this interplay or neurobiology as fundamental to humans, we also then need to consider gender an expression of an individual’s unique phenotype (which may or may not be congruent with their genotype) and part of a continuum. When we collectively acknowledge and accept a person’s social and emotional need and right, to express themself as their most authentic version of ‘me’, we can embrace what gender means to them. We should also be prepared for incongruence in this space, whereby the phenotype being expressed may not always co-align with the genetic ‘card deal’ (genotype). Kaufman et al 1 have examined the distinction between sex and gender and how this may impact research outputs when the terms are used interchangeably and not distinctly. Gender is a spectrum that includes social constructs and recognises cognitive overlays that shape its expression, whereas sex is more narrowly linked to chromosomal distribution. 1 Considerations in gender assignment also need to include how to categorise and respect non-traditional sexual assignments such as intersex, third gender, transgender or non-binary individuals.
This is relevant as we pursue understanding of genetically-coded disease while still working to provide holistic patient management. Benchmark normative data informs diagnostic pathways, and are often presented with gender as a binary choice – male or female, based on chromosomal distribution. This differentiation is important in many physical attributes but leaves us with a question of how to interpret data that are anchored in quantitative physical aspects but don’t include any weighting or expression of socioemotional overlays or behaviours. This becomes increasingly murky and confusing where individuals have opted for gender-affirming hormone therapies (GAHT) that can include powerful hormonal products with the ability to influence gene expression and cellular behaviours. How do we then determine if the parameters measured at any given time are ‘normal’? Should we use cis-gender data based on birth gender assignment in individuals that have utilised GAHT or compare metrics to the chosen gender-identity normative data or should we develop and utilise specific trans-gender normative data (as yet unavailable in many situations)?
Patel et al have raised this point in their commentary ‘Breaking the Binary: rethinking sex-matched norms in swallowing assessments for gender-diverse patients’ and speak to this issue by examining and presenting 3 patients identified as gender diverse, who underwent quantitative fluoroscopic swallowing assessments in their Institution. Two of 3 patients were receiving GAHT. Major differences were identified in pharyngeal area and hyoid motion metrics when comparing obtained measures against reference measures of either birth-assigned gender or present transgender assignation. When gender assignations were changed and then re-applied to the collected fluoroscopic data, some measures that were considered within the normal range for 1 gender, moved outside 1 or 2 standard deviations when the alternate gender norms were used. Both pharyngeal area and hyoid kinematics have been previously identified as showing gender-based differences, which is thought to relate directly to inherent size differences.2-4 Authors who acknowledge these differences have suggested normalising fluoroscopic measures to individual internal landmarks (rather than a normative dataset) to deal with physical size differences, as there is a broad range of sizes in cis-gender adults.3,4
This concept has been raised and investigated in other physical systems. For example in brain MR examinations of 803 non-hormonally treated transgender individuals and cis-gender men and women, there were detectable variations in brain volumes and surface area, between cis-gender and trans-gender groups. Trans-gender data presented as a unique phenotype, and did not match either cis-gender normative measures, but rather exhibited a third ‘blended’ phenotype. 5 In behavioural studies examining Eating Disorders behaviour of cis- and trans-gender adults, differences were found in types of eating limitation, such as greater diet limitation in transgender women than in cis-gender women, but less excessive exercise in transgender versus cis-gender females. 6
Patel et al.’s commentary raises a salient point. As we continue to see a wider interpretation of gender in our communities, we will need to consider how research data is managed and categorised, and how we use and interpret this in our own clinical practices. Research data needs to be anchored by reliable, detectable and preferably easily repeatable, data points. Researchers in other sites should be able to interpret whether they could also use the same metric reliably in their own unique populations. Generally these traits are possessed by size-based measures, whether it is absolute growth or output. However, Science now has the ability to influence gene expression and may be able to ‘power up’ or ‘power down’ transcription and expression, affecting the maximum attainable values and range. This discrepancy may potentially ‘confuse’ our reliance on gender-anchored measures that typically associate with maximum outputs.
Researchers need to open their minds to larger variation in gender categorisations and look to accurately reflect these variations. This suggests that acquisition of benchmark datasets in both disease and health states, for non-traditional and gender-diverse groups, should be a research focus for us all. Once established, these normative datasets will provide confidence for investigators looking to personalise care strategies, and incorporate holistic patient-centred care into everyday practice. It will allow us to see all the colours of the rainbow, not just black and white.
