Every cell has a genetic sex that is determined at the time of fertilization. However, the natal sex of cells may not match the hormonal environment in which they reside in transgender individuals. This discordance provides a unique opportunity to study the short- and long-term effects across a range of cellular functions, health conditions, physiologic processes and psychosocial outcomes to the benefit of transgender and cisgender communities. While there is a growing body of knowledge as the literature on sex differences in virtually every organ system accumulates, there remains a paucity of data on the effect of cross hormonal therapy on cellular function in transgender individuals. Beyond cellular function, the effect of cross hormonal therapy on neuroanatomy, the interpretation of neuropsychological assessments or even the effect of daily stressors of stigma and discrimination on long-term neurocognitive function remain unclear. In 2011 the Institute of Medicine indicated that transgender adults were an understudied population and in critical need of more biomedical and population health research, yet the experience of stigma, discrimination, microaggressions, limited access to culturally competent care continue to make this an unfulfilled mandate. In addition to using a life course perspective, it is essential to identify research gaps and formulate a responsive research agenda while maintaining scientific rigor and respectful involvement of the population under study. None of this, however, will enhance the participation of transgender communities in biomedical research until the transgender and biomedical research communities can engage in open, respectful and bidirectional dialogue. From respectful, sensitive and appropriate health care to culturally competent research engagement from study inception to data dissemination, transgender communities can make an important and valuable contribution to biomedical research. Inclusion of their voices at all levels, including investigators from transgender communities, are essential to advance this much overdue scientific agenda. Transgender, cisgender and the biomedical research communities will all benefit from a more inclusive and expansive research agenda.

Keywords: Biomedical Research; Cisgender; Sex Differences; Transgender; Vulnerable.

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