The need for an intersectionality framework in precision medicine research.

Precision medicine research has seen growing efforts to increase participation of communities that have been historically underrepresented in biomedical research. Marginalized racial and ethnic communities have received particular attention, toward the goal of improving the generalizability of scientific knowledge and promoting health equity. Against this backdrop, research has highlighted three key issues that could impede the promise of precision medicine research: issues surrounding (dis)trust and representation, challenges in translational efforts to improve health outcomes, and the need for responsive community engagement. Existing efforts to address these challenges have predominantly centered on single-dimensional demographic criteria such as race, ethnicity, or sex, while overlooking how these and additional variables, such as disability, gender identity, and socioeconomic factors, can confound and jointly impact research participation. We argue that increasing cohort diversity and the responsiveness of precision medicine research studies to community needs requires an approach that transcends conventional boundaries and embraces a more nuanced, multi-layered, and intersectional framework for data collection, analyses, and implementation. We draw attention to gaps in existing work, highlight how overlapping layers of marginalization might shape and substantiate one another and affect the precision-medicine research cycle, and put forth strategies to facilitate equitable advantages from precision-medicine research to diverse participants and internally heterogeneous communities.

Getting Precise about Gender and Sex Measurement: A Primer for Epidemiologists.

Accurately measuring gender and sex is crucial in public health and epidemiology. Iteratively reexamining how variables-including gender and sex-are conceptualized and operationalized is necessary to achieve impactful research. Reexamining gender and sex advances epidemiology toward its goals of health promotion and disease elimination. While we cannot reduce the complexities of sex and gender to simply an issue of measurement, striving to capture these concepts and experiences accurately must be an ongoing dialogue and practice-to the benefit of the field and population health. We assert that epidemiology must counteract misconceptions and accurately measure gender and sex in epidemiology. We aim to summarize existing critiques and guiding principles in measuring gender and sex that can be applied in practice.

Experiences of hereditary cancer care among transgender and gender diverse people: "It's gender. It's cancer risk it's everything".

Transgender and gender diverse (TGD) individuals are a significant yet underrepresented population within genetic counseling research and broader LGBTQI+ health studies. This underrepresentation perpetuates a cycle of exclusion from the production of medical knowledge, impacting the quality and equity of care received by TGD individuals. This issue is particularly poignant in cancer genetic counseling, where TGD individuals with elevated cancer risk receive risk assessment, counseling, and referral to support based on risk figures and standards of care developed for cisgender individuals. The experiences of TGD individuals navigating inherited cancer syndromes remain largely undocumented in medical literature, posing challenges to the provision of inclusive care by genetics providers. To bridge this knowledge gap, we conducted a cross-sectional qualitative study. Nineteen semi-structured interviews were held with gender diverse adults having hereditary cancer syndromes, family histories of such syndromes, or personal histories of chest cancer. Our study employed thematic analysis using combined inductive and deductive methods to illuminate how hereditary cancer care intersects with participants' gender identities, gender expression, and gender-affirming care experiences. Participants reflected on care experiences that felt affirming or triggered gender dysphoria. Participants also discussed the interplay between risk-reducing mastectomy and top surgery, exploring co-emergent dynamics between cancer risk management and gender expression. Significantly, participants identified actionable strategies for healthcare providers to enhance support for gender diverse patients, including the mindful use of gendered language, collaborative decision-making, and conveying allyship. These findings offer valuable insights into tailoring genetic counseling to meet the unique needs of TGD individuals, advancing the path toward inclusive and appropriate care for LGBTQI+ individuals with hereditary cancer syndromes.

Mapping Community-Engaged Implementation Strategies with Transgender Scientists, Stakeholders, and Trans-Led Community Organizations.

PURPOSE OF REVIEW: Pre-exposure prophylaxis (PrEP) represents one of the most effective methods of prevention for HIV, but remains inequitable, leaving many transgender and nonbinary (trans) individuals unable to benefit from this resource. Deploying community-engaged PrEP implementation strategies for trans populations will be crucial for ending the HIV epidemic. RECENT FINDINGS: While most PrEP studies have progressed in addressing pertinent research questions about gender-affirming care and PrEP at the biomedical and clinical levels, research on how to best implement gender-affirming PrEP systems at the social, community, and structural levels remains outstanding. The science of community-engaged implementation to build gender-affirming PrEP systems must be more fully developed. Most published PrEP studies with trans people report on outcomes rather than processes, leaving out important lessons learned about how to design, integrate, and implement PrEP in tandem with gender-affirming care. The expertise of trans scientists, stakeholders, and trans-led community organizations is essential to building gender-affirming PrEP systems.

Health and Health Care Among Transgender Adults in the United States.

Transgender (trans) communities in the USA and globally have long organized for health and social equity but have only recently gained increased visibility within public health. In this review, we synthesize evidence demonstrating that trans adults in the USA are affected by disparities in physical and mental health and in access to health care, relative to cisgender (nontrans) persons. We draw on theory and data to situate these disparities in their social contexts, explicating the roles of gender affirmation, multilevel and intersectional stigmas, and public policies in reproducing or ameliorating trans health disparities. Until recently, trans health disparities were largely made invisible by exclusionary data collection practices. We highlight the importance of, and methodological considerations for, collecting inclusive sex and gender data. Moving forward, we recommend routine collection of gender identity data, an emphasis on intervention research to achieve trans health equity, public policy advocacy, and investment in supporting gender-diverse public health leadership.

Queering genomics: How cisnormativity undermines genomic science.

Over the past century, genetics and genomics ("genomics") have contributed significantly to our knowledge of human biology and disease. Genomics has also bolstered inaccurate and harmful arguments about "essential" differences between socially defined groups. These purported differences have reinforced class hierarchies and justified the mistreatment of groups such as Black people, Indigenous people, and other people of color and/or people with disabilities. With this history in mind, we explore how genomics is used to reinforce scientifically unsound understandings of the relationship between two fundamental aspects of the human experience: sex and gender. We argue that imprecise, inaccurate practices for collecting data and conducting genomic research have adversely influenced genomic science and can contribute to the stigmatization of people whose sex and/or gender challenge binary expectations. The results have been to preclude transgender and intersex people from accessing high-quality, evidence-based healthcare and to hinder their participation in scientifically sound research. In this perspective, we use the lens of queer theory to render this situation more visible. First, we highlight the theoretical contributions queer theory can make to genomic science. Second, we examine practices in research and clinical genomics that exclude and stigmatize transgender and intersex people. Third, we highlight the ways that many current genomic research practices generate false conclusions that are used to support unjust public policies. We conclude by recommending ways that clinicians and researchers can-and should-harness the scientific, social, and cultural power of genomics to advance knowledge and improve lives across the spectra of sex and gender.

First They Came for Us All: Responding to Anti-Transgender Structural Violence With Collective, Community-Engaged, and Intersectional Health Equity Research and Advocacy.

This article is a call for collective action across health equity researchers and advocates to build a more just world. We attempt to make sense of senseless structural and interpersonal brutality in the context of the current political climate across the United States, whereby the spectrum of gender nonconformity has been and continues to be stigmatized. From drag performance to transgender identities to gender-affirming health care, extremists have instrumentalized primary levers of democracy-the courts, legislatures, and social media-to attempt to outlaw and eradicate gender expansiveness and those who provide forms of support and care, including gender-affirming medical care, to transgender, nonbinary, and gender-expansive (TNBGE) individuals.

Health status of transgender people globally: A systematic review of research on disease burden and correlates.

BACKGROUND AND OBJECTIVES: Transgender and gender diverse (trans) health research has grown rapidly, highlighting the need to characterize the scientific evidence base. We conducted a systematic review of peer-reviewed research on disease burden and correlates in trans adolescents and adults over a 20-month period to identify knowledge gaps and assess methodological characteristics including measurement of gender identity, community engagement, and study quality. DATA SOURCES, ELIGIBILITY CRITERIA, AND SYNTHESIS METHODS: We searched seven databases using terms related to (a) transgender populations and (b) health or disease. Eligible studies were in English, French, or Spanish and reported original quantitative data on mental health or substance use conditions, infectious diseases, or non-communicable conditions in at least 25 trans individuals aged 15+. Quality assessment was performed in duplicate on a 10% sample of articles and findings were summarized using narrative synthesis. RESULTS: The 328 included studies were conducted in 45 countries, with most from North America (54%) and limited research from South Asia (3%), Sub-Saharan Africa (3%), and the Middle East and North Africa (2%). Most studies used cross-sectional designs (73%) and convenience sampling (65%). Only 30% of studies reported any form of community engagement. Mental health and substance use disorders were the most studied area (77% of studies) and non-communicable conditions the least (16%). Available data indicated that trans populations experience high disease burden with considerable heterogeneity within and across settings. Of 39 articles assessed for quality, 80% were rated as fair, 18% as poor, and 3% as good quality. CONCLUSIONS AND IMPLICATIONS: Geographic, gender-specific, and topical gaps remain in trans health, but we found more research from African countries, with transmasculine people, and on non-communicable conditions than previous syntheses. Areas for growth in trans health research include community engagement, non-binary health, chronic and age-related conditions, and health determinants. REGISTRATION: PROSPERO CRD42021234043.

Advancing genomics to improve health equity.

Health equity is the state in which everyone has fair and just opportunities to attain their highest level of health. The field of human genomics has fallen short in increasing health equity, largely because the diversity of the human population has been inadequately reflected among participants of genomics research. This lack of diversity leads to disparities that can have scientific and clinical consequences. Achieving health equity related to genomics will require greater effort in addressing inequities within the field. As part of the commitment of the National Human Genome Research Institute (NHGRI) to advancing health equity, it convened experts in genomics and health equity research to make recommendations and performed a review of current literature to identify the landscape of gaps and opportunities at the interface between human genomics and health equity research. This Perspective describes these findings and examines health equity within the context of human genomics and genomic medicine.

State-level heterogeneity in associations between structural stigma and individual health care access: A multilevel analysis of transgender adults in the United States.

OBJECTIVE: State-level variation in how restrictive policies affect health care access for transgender populations has not been widely studied. Therefore, we assessed the association between structural stigma and four measures of individual health care access among transgender people in the United States, and the extent to which structural stigma explains state-level variability. METHODS: Data were drawn from the 2015-2019 Behavioral Risk Factor Surveillance System and the Human Rights Campaign's State Equality Index. We calculated weighted proportions and conducted multilevel logistic regression of individual heterogeneity and discriminatory accuracy. RESULTS: An increase in the structural stigma score by one standard deviation was associated with lower odds of health care coverage (OR = 0.80; 95% CI: 0.66, 0.96) after adjusting for individual-level confounders. Approximately 11% of the total variance for insurance coverage was attributable to the state level; however, only 18% of state-level variability was explained by structural stigma. Adding Medicaid expansion attenuated the structural stigma-insurance association and explained 22% of state-level variation in health insurance. For the remaining outcomes (usual source of care, routine medical check-up, and cost-related barriers), we found neither meaningful associations nor considerable between-state variability. CONCLUSIONS: Our findings support the importance of Medicaid expansion and transgender-inclusive antidiscrimination protections to enhance health care insurance coverage. From a measurement perspective, however, additional research is needed to develop and validate measures of transgender-specific structural stigma to guide future policy interventions.

Utilization and Costs of Gender-Affirming Care in a Commercially Insured Transgender Population.

Many transgender people need specific medical services to affirm their gender. Gender-affirming health care services may include mental health support, hormone therapy, and reconstructive surgeries. Scant information is available about the utilization or costs of these services among transgender people, which hinders the ability of insurance regulators, health plans, and other health care organizations to plan and budget for the health care needs of this population and to ensure that transgender people can access medically necessary gender-affirming care. This study used almost three decades of commercial insurance claims from a proprietary database containing data on more than 200 million people to identify temporal trends in the provision of gender-affirming hormone therapy and surgeries and to quantify the costs of these services.

Will clinical standards not be part of the choir? Harmonization between the HL7 gender harmony project model and the NASEM measuring sex, gender identity, and sexual orientation report in the United States.

OBJECTIVES: To propose an approach for semantic and functional data harmonization related to sex and gender constructs in electronic health records (EHRs) and other clinical systems for implementors, as outlined in the National Academies of Sciences, Engineering, and Medicine (NASEM) report Measuring Sex, Gender Identity, and Sexual Orientation and the Health Level 7 (HL7) Gender Harmony Project (GHP) product brief "Gender Harmony-Modeling Sex and Gender Representation, Release 1." MATERIALS AND METHODS: Authors from both publications contributed to a plan for data harmonization based upon fundamental principles in informatics, including privacy, openness, access, legitimate infringement, least intrusive alternatives, and accountability. RESULTS: We propose construct entities and value sets that best align with both publications to allow the implementation of EHR data elements on gender identity, recorded sex or gender, and sex for clinical use in the United States. We include usability- and interoperability-focused reasoning for each of these decisions, as well as suggestions for cross-tabulation for populations. DISCUSSION AND CONCLUSION: Both publications agree on core approaches to conceptualization and measurement of sex- and gender-related constructs. However, some clarifications could improve our ability to assess gender modality, alignment (or lack thereof) between gender identity and assigned gender at birth, and address both individual-level and population-level health inequities. By bridging the GHP and NASEM recommendations, we provide a path forward for implementation of sex- and gender-related EHR elements. Suggestions for implementation of gender identity, recorded sex or gender, and sex for clinical use are provided, along with semantic and functional justifications.

Gender affirming hormone therapy dosing behaviors among transgender and nonbinary adults.

Gender-affirming hormones have been shown to improve psychological functioning and quality of life among transgender and nonbinary (trans) people, yet, scant research exists regarding whether and why individuals take more or less hormones than prescribed. Drawing on survey data from 379 trans people who were prescribed hormones, we utilized multivariable logistic regression models to identify factors associated with hormone-dosing behaviors and content analysis to examine the reasons for dose modifications. Overall, 24% of trans individuals took more hormones than prescribed and 57% took less. Taking more hormones than prescribed was significantly associated with having the same provider for primary and gender-affirming care and gender-based discrimination. Income and insurance coverage barriers were significantly associated with taking less hormones than prescribed. Differences by gender identity were also observed. Addressing barriers to hormone access and cost could help to ensure safe hormone-dosing behaviors and the achievement trans people's gender-affirmation goals.

Hormone Therapy, Mental Health, and Quality of Life Among Transgender People: A Systematic Review.

We sought to systematically review the effect of gender-affirming hormone therapy on psychological outcomes among transgender people. We searched PubMed, Embase, and PsycINFO through June 10, 2020 for studies evaluating quality of life (QOL), depression, anxiety, and death by suicide in the context of gender-affirming hormone therapy among transgender people of any age. We excluded case studies and studies reporting on less than 3 months of follow-up. We included 20 studies reported in 22 publications. Fifteen were trials or prospective cohorts, one was a retrospective cohort, and 4 were cross-sectional. Seven assessed QOL, 12 assessed depression, 8 assessed anxiety, and 1 assessed death by suicide. Three studies included trans-feminine people only; 7 included trans-masculine people only, and 10 included both. Three studies focused on adolescents. Hormone therapy was associated with increased QOL, decreased depression, and decreased anxiety. Associations were similar across gender identity and age. Certainty in this conclusion is limited by high risk of bias in study designs, small sample sizes, and confounding with other interventions. We could not draw any conclusions about death by suicide. Future studies should investigate the psychological benefits of hormone therapy among larger and more diverse groups of transgender people using study designs that more effectively isolate the effects of hormone treatment.

Prevalence and associations of COVID-19 testing in an online sample of transgender and non-binary individuals.

BACKGROUND: Testing for COVID-19 and linkage to services is fundamental to successful containment and control of transmission. Yet, knowledge on COVID-19 testing among transgender and non-binary communities remains limited. METHODS: Between October 2020 and November 2020, we examined the prevalence and associations of COVID-19 testing in an online sample of transgender and non-binary people (n=536). Multivariable hierarchical logistic regression analyses examined associations between COVID-19 testing and participants' sociodemographic, mental health, substance use, gender affirmation, economic changes and healthcare experiences. RESULTS: Prevalence of COVID-19 testing in this sample was 35.5% (n=190/536). In the final model, transgender and non-binary participants from upper socioeconomic income background and Europe, who reported having active alcohol use disorder, limited access to gender-affirming surgery, had more than 20% reduction in income, and experienced mistreatment in a health facility due to gender identity had significantly increased odds of COVID-19 testing (all p<0.05); those who reported recent tobacco use had significantly lower odds of COVID-19 testing (p=0.007). CONCLUSIONS: These findings highlight structural disparities in COVID-19 testing and reinforce the importance of increasing testing strategies for transgender and non-binary populations.

The Affordable Care Act and Its Impact on Plastic and Gender-Affirmation Surgery.

SUMMARY: The Affordable Care Act's provisions have affected and will continue to affect plastic surgeons and their patients, and an understanding of its influence on the current American health care system is essential. The law's impact on pediatric plastic surgery, craniofacial surgery, and breast reconstruction is well documented. In addition, gender-affirmation surgery has seen exponential growth, largely because of expanded insurance coverage through the protections afforded to transgender individuals by the Affordable Care Act. As gender-affirming surgery continues to grow, plastic surgeons have the opportunity to adapt and diversify their practices.