6

Common Co-occurring Conditions and Impacts of Gender-Affirming Care on Chronic Conditions in Transgender and Gender Diverse Populations

Research demonstrates that, compared with cisgender populations, transgender and gender diverse (TGD) people suffer from more chronic health conditions, experience higher rates of health problems related to substance use and mental illness, and have higher prevalence and earlier onset of chronic disease (Cicero et al., 2020; Pinna et al., 2022; Reisner et al., 2016a; Rich et al., 2020; Scheim et al., 2022). The statement of task asks the committee to describe common co-occurring conditions among individuals seeking, undergoing, or under the effects of gender-affirming care. This chapter presents the available evidence on common chronic health conditions that may co-occur across the life course for TGD populations compared with cisgender populations and describes how gender-affirming treatment and care can impact these conditions. In addition, within each section, the chapter examines appropriate assessment of these conditions among TGD populations and describes substantial research gaps that limit understanding of appropriate management, outcomes, and disparities.

The chapter begins with an examination of co-occurring mental health conditions, followed by chronic conditions related to physical health. It concludes by examining how multilevel stigma and structural factors shape the disproportionate burden of disease in this population and describing several theories or frameworks that are useful in conceptualizing and understanding TGD health disparities, including those among multiply marginalized groups.

Several additional and important co-occurring conditions are not explored in this chapter because they are discussed elsewhere in the report. Chapter 5 describes the impact of gender-affirming care on a number of

important health issues, including cancer, bone health/osteoporosis, fertility, and sexual function. Part III of this report examines specific chronic conditions—including respiratory disorders (Chapter 8), chronic kidney disease (Chapter 10), and cancers of the reproductive tract (Chapter 11)—all of which could be considered co-occurring conditions for TGD people. Finally, Chapter 12 reviews certain gynecological manifestations of HIV, whereas this chapter includes a discussion of HIV as a more general concern for TGD people.

This chapter does not explore co-occurring conditions for people with variations in sex traits (VSTs). Some VSTs have notable co-occurring conditions, and where relevant, these are described in Chapter 7 and in the disease-specific chapters in Part III. Given the heterogeneity of conditions under the umbrella of VSTs, however, it is not feasible to draw broad conclusions about co-occurring conditions that span populations with VSTs. Therefore, this chapter focuses only on TGD people.

CO-OCCURRING MENTAL HEALTH CONDITIONS

Mental health is one of the most highly researched categories of health conditions in TGD populations. In a systematic review of global chronic disease burden in TGD people, Rich and colleagues (2020) found that mental health (specifically anxiety and mood disorders) and substance use disorders were the focus of most research—80 percent of studies included in the review (74 of 96 studies)—among TGD people (Rich et al., 2020). Overall, studies indicate a high prevalence of mental health conditions among TGD people compared with cisgender controls.¹

The following sections present an overview of the data related to depression and anxiety, suicidality and nonsuicidal self-harm, posttraumatic stress disorder (PTSD), substance use disorders, and eating disorders in TGD populations. Throughout, this section describes how multilevel stigma shapes the disproportionate burden of mental health in the TGD population.

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¹ Co-occurring mental health conditions (and physical health conditions as well) may appear to be more common in TGD populations because much of the research identifies TGD individuals using International Classification of Diseases and Related Health Problems (ICD) codes among clinical populations (i.e., populations that have sought gender-affirming care and, thus, have a related ICD code present in their medical record, as described in detail Chapter 3 of this report). The true prevalence of health conditions in the population at large may differ, as TGD populations who have not sought gender-affirming care (because of personal preferences or lack of access/resources) are not represented in most available studies (as this population is unlikely to have a TGD-identifying ICD code in their medical record). TGD populations that seek gender-affirming care potentially have more opportunity to receive various other diagnoses, as compared to the general TGD population, through repeated contact with clinicians and greater engagement with the health care system.

Prevalence

Depression and Anxiety

In a large cohort of TGD veterans (N = 5,135) identified in the Veterans Health Administration’s (VHA’s) electronic health record database for 1996–2013 (hereafter referred to as the “VHA TGD cohort”), statistically significant disparities were present between TGD veterans and cisgender veteran controls for major depression (adjusted odds ratio [aOR] 4.03; 95% confidence interval [CI] 3.73–4.35), other depression (aOR 4.55; 95% CI 4.21–4.92), and panic disorder (aOR 2.06; 95% CI 1.80–2.36) (Brown and Jones, 2016). Other large cohort studies have found similarly high rates of depression and anxiety in TGD people. In a large cohort of TGD Medicare beneficiaries (N = 7,454) (hereafter referred to as the “TGD Medicare cohort”), Dragon and colleagues (2017) found that TGD beneficiaries compared with their cisgender counterparts had higher observed percentages of depression (76.3 vs. 28.8 percent in cisgender beneficiaries) and anxiety (62.4 vs. 20.2 percent). Finally, in a U.S. retrospective/prospective cohort of TGD people (hereafter referred to as the “STRONG cohort”), baseline rates of depression and anxiety were much higher for both transgender females (Table 6-1) and transgender males (Table 6-2) (Quinn et al., 2017). A 2023 cross-sectional analysis using data from the National Institutes of Health All of Us Research Program (N = 372,082) (hereafter referred to as “All of Us Research Program”) adds to the literature showing higher odds of anxiety and depression among TGD populations compared with cisgender and heterosexual controls (Tran et al., 2023).

TABLE 6-2 Frequency of Health Outcomes in the STRONG Transgender Male (TM) Cohort Relative to Matched Reference (Ref.) Groups

^a Percentages do not add to 100% because of overlapping categories.

^b Combined diagnoses of self-inflicted injury, self-inflicted injury/poisoning, and possible self-inflicted injury.

SOURCE: Adapted from Quinn et al., 2017.

Suicidality and Nonsuicidal Self-Harm

Both suicidality (ideation, planning, attempt, and completion) and self-harm are more common among TGD people, especially TGD youth, than among cisgender people. The TransPop study, the first national probability sample of TGD adults in the United States, found high rates of recent suicidal ideation (44.4 percent; 95% CI 35.8–53.0), recent suicide attempt (6.9 percent; 95% CI 2.3–11.5), and recent nonsuicidal self-injury (21.4 percent; 95% CI 14.5–28.4) (Kidd et al., 2023). Compared with a cisgender comparison sample in TransPop, TGD participants had 5 times higher odds of recent suicidal ideation (aOR 5.1; 95% CI 2.7–9.6), almost 7 times the odds of lifetime suicidal ideation (aOR 6.7; 95% CI 3.8–11.7), more than 4 times the odds of lifetime suicide attempts (aOR 4.4; 95% CI 2.4–8.0), and 13 times the odds of nonsuicidal self-injury (aOR 13.0; 95% CI 4.8–35.1).

As shown in Tables 6-1 and 6-2, the STRONG cohort study found a higher baseline prevalence of suicidal ideation (6.7 percent) and self-harm (4.2 percent) in transgender male participants compared with transgender female participants (suicidal ideation: 5.0 percent; self-harm: 2.2 percent), and prevalence in both TGD groups was higher than in comparison groups (Quinn et al., 2017). Three systematic reviews further indicate that TGD people compared with cisgender people have consistently higher rates of suicidality and nonsuicidal self-injury, and that transgender men versus transgender women have higher rates of nonsuicidal self-injury (Marconi et al., 2023; Marshall et al., 2016; Pinna et al., 2022).

Posttraumatic Stress Disorder (PTSD)

The authors of a recent systematic review and meta-analysis of 27 studies (N = 31,903) estimate that LGBT study participants had higher odds of PTSD compared with cisgender, heterosexual controls (odds ratio [OR] 2.20; 95% CI 1.85–2.60), and that TGD study participants had even higher odds of PTSD compared with their lesbian, gay, and bisexual peers (OR 2.52; 95% CI 2.22–2.87) (Marchi et al., 2023). The VHA TGD cohort indicated that TGD veterans had nearly three times higher odds of having PTSD compared with cisgender controls (aOR 2.82; 95% CI 2.60–3.06) (Brown and Jones, 2016). In the TGD Medicare cohort, 22.7 percent of TGD Medicare beneficiaries had PTSD, compared with 1.6 percent of cisgender beneficiaries (Dragon et al., 2017). Similar results were found in a retrospective medical record review (N = 79), with PTSD affecting up to 22.8 percent of TGD adolescents who were seeking care from a large, urban multidisciplinary gender program (Nahata et al., 2017).

Substance Use Disorders

TGD populations have higher rates of substance and alcohol abuse and tobacco use relative to their cisgender counterparts. In the VHA TGD cohort, for example, TGD veterans had higher odds of alcohol abuse (aOR 1.68; 95% CI 1.55–1.82) and tobacco use (aOR 1.46; 95% CI 1.37–1.57) compared with cisgender controls (Brown and Jones, 2016), and within the TGD Medicare cohort, TGD Medicare beneficiaries had higher observed percentages of substance use disorders than were observed among cisgender beneficiaries (26.6 vs. 4.2 percent) (Dragon et al., 2017).

A review that included 41 studies found “high and excess prevalence of substance use” in TGD people compared with cisgender people, but could not pool any of the effect sizes (Connolly and Gilchrist, 2020). Such findings may be skewed by unrepresentative convenience samples, however (Scheim et al., 2022). The author of one review reported that community surveys of TGD substance use found high rates of smoking, alcohol abuse, and drug use (Scheim et al., 2022). In a scoping review examining substance use in TGD youth (aged 10–24), findings showed high to moderate use of alcohol, binge drinking, cigarettes and e-cigarettes, and marijuana (Fahey et al., 2023). In contrast to these studies, Kidd and colleagues (2023) found alcohol and drug use outcomes to be similar for TGD and cisgender adults in an analysis using TransPop study data (N = 274). While these authors report hazardous drinking among TGD people (28.2 percent; 95% CI 21.2–35.2 percent) and problematic drug use (31.2 percent; 95% CI 23.8–38.7 percent), these rates were similar to those among cisgender groups. In addition, some research has found lower rates of substance use among certain TGD populations:

while data from All of Us Research Program show that gender diverse people assigned male at birth (aOR 1.76; 95% CI 1.15–2.67) and transgender women (aOR 2.02; 95% CI 1.54–2.65) had significantly higher odds of having a substance use disorder compared with cisgender heterosexual women, the data revealed gender diverse people assigned female at birth (aOR 0.35; 95% CI 0.24–0.52) and transgender men (aOR 0.65; 95% CI 0.49–0.87) had lower odds of substance use disorder compared with cisgender heterosexual men (Tran et al., 2023). Further research is needed to understand differences in substance use among various TGD populations.

Eating Disorders

TGD populations have consistently higher prevalence of eating disorders and disordered eating compared with cisgender populations, although prevalence estimates vary (Coelho et al., 2019; Heiden-Rootes et al., 2023; Jones et al., 2016; Rasmussen et al., 2023). In the VHA TGD cohort, transgender veterans had double the odds of having an eating disorder compared with matched cisgender controls (aOR 2.01; 95% CI 1.58–2.54) (Brown and Jones, 2016). A systematic review (24 studies) and meta-analysis (14 studies) calculated an overall eating disorder prevalence of 17.7 percent in TGD people (Rasmussen et al., 2023). This figure is significantly higher when compared with the general population, as a previous meta-analysis estimated a 1.01 percent (95% CI 0.54–1.89 percent) lifetime eating disorder prevalence in the general population (Qian et al., 2013). Another review estimated that 20–50 percent of TGD people had disordered eating, more than 30 percent screened positive for eating disorders, and 2–12 percent had an eating disorder diagnosis (Keski-Rahkonen, 2023).

Eating disorders do not affect TGD populations evenly: one systematic review revealed that transgender men tend to experience a higher prevalence of eating disorders compared with transgender women (Rasmussen et al., 2023). Another study showed that transgender youth aged 8–25 were more likely than their cisgender counterparts to be diagnosed with an eating disorder, with an estimated prevalence of 2–18 percent (Coelho et al., 2019). Sub-populations not well represented in the research on eating disorders include nonbinary people, racially and ethnically minoritized groups, neurodivergent groups, and TGD people living in specific family and cultural contexts that have standards of femininity and masculinity that may impact eating behaviors (Heiden-Rootes et al., 2023; Obarzanek and Munyan, 2021).

Risk and Protective Factors

The gender minority stress model posits that gender minorities experience anticipated, internalized, and enacted stigma because of the stigma

society places on minority gender identities, which leads to worse physical and mental health outcomes (Connolly and Gilchrist, 2020; Testa et al., 2015). For TGD youth especially, these repeated traumatic experiences compound over time, leading to substance use, depression, stress, shame, and loneliness (Ramos and Marr, 2023). In TGD youth, victimization experiences both related and unrelated to gender identity were found to be associated with substance use (Fahey et al., 2023). For racial minority groups and others with stigmatized identities (e.g., disability, neurodivergence), these stressors affect them synergistically, leading to even worse physical and mental health outcomes and increased barriers to care (Bowleg, 2012; Crenshaw, 1991; Mulcahy et al., 2022; Wesp et al., 2019). Specific research related to suicidality, PTSD, and eating disorders is presented below.

Suicidality and Nonsuicidal Self-Injury

Minority stress, stigma, discrimination, social rejection (Marconi et al., 2023), and thwarted belongingness are associated with increased suicidality and nonsuicidal self-injury (Phillip et al., 2022). One meta-analysis tested the associations of constructs of the minority stress model (internalized transphobia, expectations of rejection, identity concealment) with suicidality and self-harm, finding that expectations of rejection and internalized transphobia most strongly predicted suicidal ideation (Pellicane and Ciesla, 2022). TGD youth are especially vulnerable, as they may face family rejection without yet having built a strong social circle of chosen family to support them. Nonsuicidal self-injury was also found to be associated with psychopathology, interpersonal problems, and low social support (Marshall et al., 2016). Conversely, social support, parental support, having at least one personal identification document with the appropriate gender marker, and ability to obtain gender-affirming medical care are all protective against suicidal ideation (Bauer et al., 2015).

Post-Traumatic Stress Disorder (PTSD)

Higher prevalence of PTSD in TGD people is due to several factors, including both acute and chronic exposures to traumatic stressors, marginalization, and discrimination (Ramos and Marr, 2023). Factors related to gender minority stress and intersectionality, noted above, are especially pertinent here, and partially explain the higher prevalence of PTSD. Other mental health issues discussed in this section, such as eating disorders, depression, anxiety, self-harm, suicide, and substance use, are interrelated with PTSD (Ramos and Marr, 2023).

TGD youth especially have higher rates of interpersonal and community-level trauma compared with their cisgender peers.

Vulnerabilities particular to TGD youth include higher adverse childhood experience scores, higher rates of family rejection (leading to substance use, mental illness, and homelessness), more childhood abuse targeted at gender nonconformity, and more bullying and victimization (Ramos and Marr, 2023).

The gender minority stress model also emphasizes that minoritized groups form community identity, pride, and resilience (Testa et al., 2015), and TGD youth often access social support, skills-building, and affirming trauma-informed services (Ramos and Marr, 2023). Support from parents, especially at younger ages, and school, peer, and community connectedness are key protective factors against trauma for TGD youth (Ramos and Marr, 2023). Similarly, community connections and social supports are important for TGD adults, as these connections may help mitigate negative experiences of violence and other traumatic stressors (Pflum et al, 2015; Sherman et al., 2020, 2022).

Eating Disorders

There are several hypotheses as to why TGD versus cisgender populations have higher rates of eating disorders. Body dissatisfaction related to gender dysphoria and the desire to appear less gendered by becoming either thinner or heavier is a common explanation (Jones et al., 2016; Obarzanek and Munyan, 2021). A desire to be recognized as their affirmed gender may cause TGD people to adopt unhealthy behaviors in an effort to prove manliness or womanliness (McGregor et al., 2023). Disordered eating may also be an attempt to regain control, especially when there are barriers to gender-affirming care (McGregor et al., 2023). Youth may use disordered eating in an attempt to delay or prevent puberty (Coelho et al., 2019); transgender men may use it to induce amenorrhea; and transgender women may internalize societal pressure for thinness in women (Obarzanek and Munyan, 2021). One review cautions providers to be aware that body dissatisfaction is not always related to sex-specific body parts (genitals), but more to chest, curves, shoulders, body hair, and other secondary sex characteristics (Jones et al., 2016). Lastly, the high stigma, discrimination, and minority stress TGD people face, and the higher burden of mental illness as a result, likely have a large impact on eating disorders and disordered eating in these populations (Keski-Rahkonen, 2023; Obarzanek and Munyan, 2021).

Social affirmation/transition and gender-affirming hormone therapy may ameliorate body image issues and eating disorders in TGD people (Heiden-Rootes et al., 2023; Jones et al., 2016; McGregor et al., 2023; Obarzanek and Munyan, 2021; Rasmussen et al., 2023). Family, peer, school connectedness, and social support may also help, but more research

is needed in this area (McGregor et al., 2023; Obarzanek and Munyan, 2021; Rasmussen et al., 2023).

Assessments

Common assessments for mental health disorders such as anxiety, depression, psychological distress, and suicidal ideation have been widely used in both cisgender and TGD populations. These assessments are not sex based, so their interpretation is the same for all populations. In the case of PTSD, however, a common assessment known as the Clinician-Administered PTSD Scale (from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) may not be appropriate for TGD people. A 2023 study tested and qualitatively explored limitations of the Clinician-Administered PTSD Scale for TGD patients; findings suggest that there may be overpathologizing or underdetection of symptoms for TGD people because discrimination-related experiences may threaten the assessment’s accuracy (Valentine et al., 2023). Instead of identifying trauma, for example, the assessment may link patient symptoms to internalized transphobia or gender identity/expression (Valentine et al., 2023).

Common assessments of substance use may also have drawbacks for these populations. While the Alcohol Use Disorder Identification Test and AUDIT-Consumption appear to be reliable for TGD populations (Dermody et al., 2023; Kuhns et al., 2020; Williams et al., 2021), they include sex-specific cutoff scores. Presently, moreover, no guidance is available for health care providers on the use of sex recorded at birth or the patient’s gender when using the Alcohol Use Disorder Identification Test (Flentje et al., 2020).

Likewise, common assessments for eating disorders may be inappropriate and inaccurate for TGD people, as they are centered on young, White, cisgender women. The traditional Eating Disorder Inventory, for example, includes items that could indicate either disordered eating or gender dysphoria, and so should not be used (McGregor et al., 2023). Instead, the SCOFF² questionnaire is genderless and can be used for TGD populations (Morgan et al., 2000), and a short seven-item version of the Eating Disorder Exam Questionnaire has been validated for gender minorities (Keski-Rahkonen, 2023).

Clinical Management and Gender-Affirming Care

The Callen-Lorde Community Health Center (2018) recommends counseling TGD patients on the potential impact of gender-affirming hormone

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² The acronym “SCOFF” is taken from the five questions asked in the assessment. See Morgan et al., 2000.

therapy (GAHT) on depression and anxiety, as these conditions may be either ameliorated or exacerbated by hormones. It also recommends that patients with active psychosis or a suicidal or homicidal plan be treated and stabilized before initiating GAHT. The Callen-Lorde guidelines note further that the mental health treatment plan should be with a trans-competent provider, as delay of GAHT may worsen distress (Callen-Lorde Community Health Center, 2018). The World Professional Association of Transgender Health (WPATH) guidelines approach mental health in a general way, encouraging appropriate care, support, and empowerment (Coleman et al., 2022).

Research shows that gender-affirming medical and/or surgical treatments can help reduce suicide risk: in one study, TGD people on hormone therapy were about half as likely to have considered suicide (relative risk 0.52; 95% CI 0.37–0.75) as those who wished to use hormones as part of gender-affirming care but were unable to access this care (Bauer et al., 2015). Even among those who have had GAHT and/or gender-affirming surgery, however, suicide attempts and deaths may remain elevated compared with the cisgender population (Asscheman et al., 2011; Dhejne et al., 2011), in part because of minority stressors (including internalized transphobia, victimization, bullying, or negative family treatment), which are significantly associated with suicidal ideation and suicide attempts among TGD individuals (de Lange et al., 2022; Pellicane and Ciesla, 2022).

Best practices for mental health providers include assessing for and treating nonsuicidal self-injury and trauma (Dickey et al., 2017), and all medical providers need to screen TGD patients for childhood trauma and toxic stress symptoms (Ramos and Marr, 2023). Neither nonsuicidal self-injury nor trauma is considered a contraindication for gender-affirming care (Dickey et al., 2017). All medical care for TGD people, not just gender-affirming care, should use trauma-informed approaches (Dickey et al., 2017; Ramos and Marr, 2023), and medical providers should assume that all TGD people have experienced trauma, including in the health care setting.

While there are guidelines for treating many mental health concerns among TGD people, research on treating substance use disorders is lacking in these populations. Multiple studies, including randomized controlled trials, have tested various treatment programs for transgender populations, targeting alcohol, tobacco, meth, stimulants, and substance use generally (Chapa Montemayor and Connolly, 2023; Coffin et al., 2020; Keuroghlian et al., 2015; Kuhns et al., 2020; Lee et al., 2014; Matson et al., 2022; Zhang et al., 2018). In many cases, although substance use treatment programs can be feasibly adapted for use in TGD populations, no rigorous outcome evaluations exist, and more research is needed in this area.

In the case of eating disorders, there are no consensus guidelines for treating TGD people, although toolkits on managing eating disorders in LGBTQ+ communities exist (Joy et al., 2023; White et al., 2023). Given the

high co-occurrence of these disorders in TGD people, however, researchers recommend screening TGD youth in gender dysphoria clinics for eating disorders, and vice versa (McGregor et al., 2023). TGD people do benefit from treatment for eating disorders, but providers must be attuned to transgender-competent care, understand minority stress, recognize co-occurring mental illness, and minimize dysphoria (Keski-Rahkonen, 2023; McGregor et al., 2023). Current treatment standards for marking progress (i.e., return of menses) may be distressing for transgender men and irrelevant for transgender women; treatment and markers of progress need to be sensitive to gender dysphoria and be individualized (Geilhufe et al., 2021). Qualitative findings indicate that TGD people have had highly negative experiences in eating disorder clinics, hide their identity or get misgendered, and find that providers do not have trans-competent knowledge (McGregor et al., 2023). As gender-affirming care may help with symptoms, TGD people with eating disorders may seek GAHT or other care concurrently with treatment for an eating disorder (Keski-Rahkonen, 2023).

Research Limitations and Gaps

As described above, anxiety and depression are well represented in the transgender health literature, while other mental health conditions, such as schizophrenic/psychotic disorders, bipolar disorder, personality disorders, and PTSD are less well studied. It should be noted that the cross-sectional nature of most studies reporting on suicidality and nonsuicidal self-injury limit the ability to interpret the study findings and establish temporality (e.g., when and why nonsuicidal self-injury occurs in TGD people). For example, prospective studies could elucidate whether nonsuicidal self-injury decreases with gender-affirming care and social acceptance.

Additional data are needed to better understand substance use among TGD populations. Many community-based studies of substance abuse rely on higher-risk, multiply marginalized populations, for whom substance use is likely higher than it is in the general TGD population (Connolly and Gilchrist, 2020). Trans-specific programming, education, and cessation resources are important (Turner et al., 2021), and high-quality, representative studies of substance use rates in TGD populations are lacking.

In the case of PTSD in TGD people, the research base is growing: in their review, Rich and colleagues (2020) included 24 studies that addressed PTSD (Rich et al., 2020), compared with only 3 such studies in a previous global review of transgender health (Reisner et al., 2016a). None of the major guidelines for TGD treatment and care address or provide recommendations for PTSD. Further research is warranted, especially among groups who are multiply marginalized.

To date, available data on eating disorders are based mostly on cross-sectional convenience samples with small sample sizes, and some of these data are not disaggregated by gender identity. Longitudinal studies that also include nonbinary people, racialized minority groups, neurodivergent people, and overweight and obese TGD people are needed (Obarzanek and Munyan, 2021; Rasmussen et al., 2023).

AUTISM AND OTHER NEURODEVELOPMENTAL DIAGNOSES

Several recent studies have estimated the prevalence of gender dysphoria in autistic people³ and the prevalence of autism/autism spectrum disorder (ASD) in TGD people. All studies concur that there is an overrepresentation of autism in transgender people (Bouzy et al., 2023) and a need to raise awareness about this association.

Prevalence

A 2023 systematic review and meta-analysis of 25 studies of children, adolescents, and adults (N = 8,662) found that ASD occurs frequently in TGD people, with a prevalence of 11 percent (95% CI, 8–16 percent), compared with approximately 1 percent in the general population (Kallitsounaki and Williams, 2023). In a large U.S. cohort study conducted in eight pediatric hospitals with more than 900,000 adolescents aged 9–18, gender dysphoria was more prevalent in autistic youth (1.1 percent) than in neurotypical (nonautistic) youth (0.6 percent). There were greater odds of a gender dysphoria diagnosis among youth with an ASD diagnosis versus those without (aOR 3.00; 95% CI 2.72–3.31) (Kahn et al., 2023). In another systematic review, 7.8 percent of children and adolescents seeking care for gender dysphoria had an ASD diagnosis—four times higher than in the general population (Bouzy et al., 2023). This review reported wide ranges for estimated ASD in TGD youth (5.5–29.6 percent in transgender adults; 6.3–27.1 percent in children/adolescents with gender dysphoria) and for gender dysphoria in autistic people (0.07–31.0 percent in adults; 0.07–5.40 percent in children/adolescents) (Bouzy et al., 2023).

Associated Factors

A variety of theories—biological, genetic, social, and psychological/cognitive—attempt to explain the high co-occurrence of ASD and gender

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³ “Autistic people” (identity-first language) rather than “people with autism” (person-first language) is a conscious choice in line with autistic activists and advocates. This parallels “transgender people” (identity first) rather than “people with gender dysphoria” or “people with transness.”

dysphoria. While certain subpopulations are overrepresented in autism diagnoses (i.e., White, middle class, assigned male sex at birth), this does not indicate the absence of autism in all other populations. A cohort study by Kahn and colleagues (2023) showed that while White youth were significantly more likely than Black or Asian youth to have co-occurring ASD and gender dysphoria, White youth in the cohort also had greater access to gender clinics and to private insurance, both of which increased the likelihood of a gender dysphoria diagnosis. The authors posit that the lack of documentation of ASD and gender dysphoria co-occurrence among Black and Asian youth could be due to disparities in health services or other demographic differences (Hadland et al., 2023; Kahn et al., 2023). Additional research is needed to determine disparities and outcomes faced by youth of color with ASD.

This same study also revealed co-occurring ASD and gender dysphoria diagnoses to be more prevalent in youth with female sex recorded at birth versus male sex recorded at birth (aOR 1.77, 95% CI 1.45–2.16) (Kahn et al., 2023). This finding stands in contrast to a body of literature showing that, overall, ASD diagnoses are higher among cisgender men compared with cisgender women; male-skewed ASD diagnoses have been attributed to possible bias in ASD diagnostic criteria toward male-typical behaviors (Haney, 2016). Kahn and colleagues (2023), therefore, posit that youth with female sex recorded at birth who exhibit male-typical behavior and/or identify as male may be more likely to be diagnosed with ASD compared with other youth with female sex recorded at birth, given current diagnostic criteria. Further research is needed to understand these possible differences by sex and what they may mean for ASD diagnosis among TGD youth.

Assessments

Strang and colleagues (2018) offer initial clinical guidelines for combined assessment of gender dysphoria and autism. Investigators encourage gender clinics to screen for autism, and for autism clinics to screen for gender dysphoria (Bouzy et al., 2023; Kallitsounaki and Williams, 2023; Strang et al., 2018). WPATH addresses autism only in the context of diagnosis of gender dysphoria in children and adolescents and the need for taking extra care to support autistic youth in fully understanding their dysphoria and transition options and consequences (Coleman et al., 2022). Others agree that TGD autistic people may need extra support with respect to tolerance of change, flexibility, planning, and social skills during the changes involved in transition, and offer ideas for ensuring that gender clinics are autism friendly (Bouzy et al., 2023). Researchers also note that LGBTQ+ autistic people (including adults) are often discredited and infantilized and told that they cannot know their LGBTQ+ identities. ASD diagnosis does not

invalidate someone’s TGD identity, and it is not appropriate to use an ASD diagnosis to prevent care; GAHT can improve difficulties associated with autism and does not exacerbate autistic traits (Bouzy et al., 2023; Hadland et al., 2023; Nobili et al., 2018).

Clinical Management and Gender-Affirming Care

As noted above, co-occurrence of ASD and gender dysphoria is not a contraindication for gender-affirming care (Bouzy et al., 2023). Rather, additional cultural sensitivity and specialized care to meet the needs associated with both autism and gender dysphoria is necessary, as both being transgender and being autistic are stigmatized, compounding minority stress and the risk of discrimination (Hadland et al., 2023) and increasing the risk of anxiety and depression (Bouzy et al., 2023). The first preliminary clinical guidelines for co-occurring autism and TGD identity in adolescents were developed using the Delphi method in 2018 (Strang et al., 2018). These guidelines provide recommendations for assessment and treatment and address some primary clinical and psychosocial challenges that may be faced by autistic TGD adolescents (Strang et al., 2018). The National LGBTQIA+ Health Education Center (2024) offers a webinar for providers on neurodiversity and the gender diverse experience.

Research Limitations and Gaps

Most attention around autism is aimed at children and adolescents, ignoring adults’ experiences and needs. Tailored services and interventions for autistic TGD people of all ages are needed, in addition to those for children and adolescents. Screening autistic people for gender dysphoria and TGD people for autism would help them access appropriate care earlier (Kallitsounaki and Williams, 2023). The disparities in access and care among racialized minorities need to be addressed as well.

There are also large gaps in research on the co-occurrence of other neurotypes and conditions, such as attention-deficit/hyperactivity disorder. Two systematic reviews on this topic found only a handful of studies (Goetz and Adams, 2022; Thrower et al., 2020).

CO-OCCURRING PHYSICAL HEALTH CONDITIONS

While the majority of the data on the health of TGD populations comes from studies focused on mental health concerns, there are some data related to chronic physical health conditions. The following sections

present research data on human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), cardiovascular conditions, metabolic and endocrine disorders, and chronic liver disease. As mentioned above, other important chronic health conditions—including cancer, respiratory disorders, and chronic kidney disease—are addressed elsewhere in this report.

HIV/AIDS

Transgender individuals continue to be disproportionately burdened by HIV, with both transgender women and transgender men showing elevated rates of HIV infection worldwide. The unique HIV prevention and care needs among TGD people are an important consideration for the health of this population.

Prevalence

Transgender women have the highest prevalence of HIV of any TGD group. Serious racial disparities exist among transgender women. According to Centers for Disease Control and Prevention (2021) estimates, 17 percent of White, 62 percent of Black, and 35 percent of Latina transgender women in the United States are living with HIV. In a systematic review of studies reporting HIV prevalence among TGD people published between January 2000 and January 2019, Stutterheim and colleagues (2021) found that transgender women were 66 times more likely to have HIV (95% CI 51.4–84.8) compared with the general population over age 15. Transgender men were almost 7 times more likely to have HIV (95% CI 3.6–13.1), compared with the general population over age 15. HIV prevalence among nonbinary and other gender diverse people is unknown.

Risk and Protective Factors

Although the majority of research on HIV among TGD people centers on transgender women, all TGD people can be at risk for acquiring or transmitting HIV, depending on type of sexual exposure (anal, vaginal, oral), presence of sexually transmitted infection and/or inflammation, and genital surgery type (e.g., neovagina risk is not well known) (Poteat et al., 2016, 2017). Research shows that transgender women are likely to engage in sexually risky behaviors (e.g., condomless sex, high number of sexual partners, sex work) that elevate HIV risk (Guadamuz et al., 2011; Naz-McLean et al., 2022; Salazar et al., 2017; Silva-Santisteban et al., 2012). Although research on transgender men is less available, it indicates sexually risky behaviors in this population as well (Bauer et al., 2012; McFarland et al., 2017, 2018; Reisner and Murchison, 2016).

In addition, changes in transgender men brought by testosterone therapy, such as vaginal dryness, may increase susceptibility to HIV infection (Reisner et al., 2016b).

The social contexts of racism, sexism, and transphobia contribute to HIV vulnerability among TGD people (Baral et al., 2013; Sevelius, 2013). Stigma and discrimination reduce access to employment opportunities, and for some, these circumstances may reach the point where sex work becomes the only option available for income (Poteat et al., 2015). The circumstances of social oppression and psychological distress may increase engagement in high-risk behavior (e.g., exchange sex, sex with a person of known HIV status, illicit injection of hormones or silicone) (Habarta et al., 2015; Poteat et al., 2017). Social gender affirmation (living full-time in one’s identified gender, with or without gender-affirming care) may also play an important role in sexual risk behavior for transgender men who have sex with cisgender men; here, transgender men may face the same social stigma and stressors that put cisgender men who have sex with men at increased risk of HIV infection (Reisner et al., 2016b).

Inadequate and uneven access to HIV testing and treatment is another important disparity to consider for TGD people living with HIV. TGD people are reported to have lower lifetime rates of HIV testing compared with cisgender gay and bisexual men (Pitasi et al., 2017). In one study examining data from the 2015 U.S. Transgender Survey (N = 26,927), 45 percent of respondents had never been tested for HIV (Olakunde et al., 2022). In another U.S. study of transgender and nonbinary people (N = 539), 26.2 percent of survey respondents had never been tested for HIV (Lacombe-Duncan et al., 2022). While rates of HIV screening in the general population are also low—in 2022, only 36.3 percent of U.S. adults over age 18 reported having ever been tested for HIV (KFF, 2022)—given the higher HIV risk profile of TGD people, HIV testing in this population is suboptimal. However, HIV testing varies between subgroups: corroborating other research (Sevelius et al., 2020), a survey conducted by Lacombe-Duncan and colleagues (2022) found that Black survey participants had a greater likelihood of having had a previous HIV test compared with White participants (aOR 0.28; 95% CI 0.09–0.86). The survey also found that participants who had experienced sexual violence were more likely to have had an HIV test (aOR 0.38; 95% CI 0.21–0.67); participants who had access to an inclusive, trans-affirming primary care provider also had increased likelihood of HIV testing (aOR 0.29; 95% CI 0.17–0.49).

These findings point to the need for trans-inclusive HIV testing practices, particularly at the point of sexual violence intervention, and the importance of educating primary care providers to be more trans affirming. Other studies show that TGD people are more likely to access HIV testing in community-based, non–health care settings, highlighting difficulties in

access to HIV prevention within the health care system and the need for expanding targeted HIV testing for TGD people outside of traditional settings (Habarta et al., 2015).

In addition, research points to the need to expand use of pre-exposure prophylaxis (PrEP) as an important part of HIV prevention among TGD people. PrEP is a safe and effective way to prevent HIV (Grant et al., 2010; Molina et al., 2015), but among TGD people eligible for PrEP, only 3 percent take it up (3.2 percent of eligible transgender women and 2.3 percent of eligible transgender men) (Sevelius et al., 2020). Furthermore, rates of PrEP discontinuation among TGD people are high: one study found 35–40 percent annual discontinuation of PrEP among sexual and gender minority people, citing housing instability and prior history of PrEP discontinuation as predictors of discontinuation (Guo et al., 2024).

Beyond testing and sustained PrEP use, TGD people may lack access to HIV treatment upon diagnosis. While limited outcomes data exist, research indicates that TGD people living with HIV are less likely to receive and adhere to antiretroviral treatment and have poorer viral suppression compared with cisgender people living with HIV (Kalichman et al., 2017; Klein et al., 2020; Melendez et al., 2006; Mizuno et al., 2015, 2017; Xia et al., 2019). In addition, some TGD people may fear that HIV medications could interfere with their GAHT, causing some to forgo HIV medication in favor of hormone therapy (Braun et al., 2017; Sevelius et al., 2016).

Taken together, all of these impediments may lead to delayed diagnosis and poorer outcomes for TGD people with HIV.

Assessments

When assessing vulnerability to HIV, University of California, San Francisco (UCSF) guidelines encourage providers and other practitioners not to assume gender or body parts or history of surgeries in TGD people or their partners (Poteat, 2016; UCSF, 2016). Gender identity and sexual orientation are two separate concepts, and TGD people can have any sexual orientation. Furthermore, TGD people can have partners of any gender identity—men, women, nonbinary, etc.—and any gender modality—transgender, cisgender, etc. (Rioux et al., 2022). Anatomy-specific questions should be asked with sensitivity (Poteat, 2016).

Clinical Management and Gender-Affirming Care

There are no clinically significant contraindications for current medications for prevention or treatment of HIV in patients receiving GAHT (Cespedes et al., 2022; Poteat, 2016). Chapter 12 examines the impact of GAHT and other gender-affirming care on HIV in greater depth.

Limitations and Gaps

Although HIV/AIDS is one of the most researched topics in transgender health, gaps in knowledge remain. The biomedical tools for filling these gaps are available, but structural barriers limit access; attention to dismantling these structural barriers is key (Poteat et al., 2017). Cisgender male partners of transgender women and men are understudied, but likely have high HIV risk—especially those who conceal their relationships and behaviors because of stigma (Poteat et al., 2021). Research on transgender men is nascent, and research on nonbinary people and HIV is nonexistent.

Cardiovascular Conditions

Prevalence

Data on cardiovascular mortality and morbidity risk in TGD populations are inconsistent and incomplete. While some studies have found a higher prevalence of myocardial infarction and cerebrovascular disease rates among transgender females relative to the general population, others have found no increased risk of myocardial infarction, stroke, or venous thromboembolism in transgender females (Asscheman et al., 2011; Dhejne et al., 2011; Getahun et al., 2018; Tran et al., 2023; Wierckx et al., 2013). For transgender men and gender nonconforming people, the risk of myocardial infarction may be the same as for the general population (Nokoff et al., 2018).

In the STRONG cohort, baseline prevalence for five cardiovascular outcomes—venous thromboembolism, stroke, myocardial infarction, peripheral artery disease, and unstable angina—was reported separately for transgender females and males (see Tables 6-3 and 6-4, respectively).

TABLE 6-3 Frequency of Cardiovascular Disease Health Outcomes in the STRONG Transgender Female (TF) Cohort Relative to Matched Reference (Ref.) Groups

^a Percentages do not add to 100% because of overlapping categories.

SOURCE: Adapted from Quinn et al., 2017.

TABLE 6-4 Frequency of Cardiovascular Disease Health Outcomes in the STRONG Transgender Male (TM) Cohort Relative to Matched Reference (Ref.) Groups

^a Percentages do not add to 100% because of overlapping categories.

SOURCE: Adapted from Quinn et al., 2017.

In both populations prevalence in all categories was similar to that in the general population (Quinn et al., 2017).

On the other hand, the TGD Medicare cohort study showed lower rates of five cardiovascular conditions in TGD compared with cisgender beneficiaries, as shown in Table 6-5 (Dragon et al., 2017).

Still other analyses have shown higher cardiovascular disease risk in TGD people. Analyses of the Behavioral Risk Factor Surveillance System have revealed that transgender men have a greater than 2-fold higher rate of myocardial infarction compared with cisgender men (aOR 2.53; 95% CI 1.14–5.63) and a 4-fold higher rate compared with cisgender women (aOR 4.90; 95% CI 2.21–10.90) (Alzahrani et al., 2019). For transgender women, Alzahrani and colleagues (2019) found a higher rate of myocardial infarction compared with cisgender women (aOR 2.56; 95% CI 1.78–3.68), but no significant difference compared with cisgender men. In addition, the VHA TGD cohort showed higher odds for several cardiovascular conditions compared with non-TGD counterparts, as shown in Table 6-6 (Brown and Jones, 2016).

TABLE 6-5 Percentage of Medicare Beneficiaries with Cardiovascular Conditions

SOURCE: Dragon et al., 2017.

TABLE 6-6 Adjusted Odds Ratio (aOR) of Cardiovascular Diseases for Transgender Veterans Seeking Veterans Health Administration Care, 1996–2013

SOURCE: Brown and Jones, 2016.

Risk and Protective Factors

A review by the American Heart Association examined the literature related to TGD people with respect to common cardiovascular risk factors (including tobacco use, physical activity, body mass index [BMI], lipid profile, and diabetes). The review found a lack of data across all factors, which limited the ability to determine disparities in cardiovascular health among TGD populations (Streed et al., 2021).

HIV is associated with increased risk for cardiovascular disease, given the high prevalence of cardiovascular risk behaviors among people living with HIV and the physiological effects of HIV disease itself (Feinstein et al., 2019). Given significantly higher rates of HIV among TGD people (as described above), it might be expected that cardiovascular disease risk would be higher in this population. While data are limited, existing research suggests that TGD people with HIV may be at higher risk for cardiovascular-related disease compared with cisgender people with HIV (Gosiker et al., 2020).

Assessments

Assessment of risk for atherosclerotic cardiovascular disease (ASCVD) is commonly used in clinical practice to aid in decision making surrounding primary prevention therapies. Assessment tools for ASCVD use either male or female reference sex when calculating risk, leaving health care providers who care for TGD people to make these decisions without clinical guidance on how best to assess these populations (Poteat et al., 2023). Likewise, other common assessments of risk for cardiovascular disease, including the

Framingham Risk Score and the Reynolds Risk Score, use sex-specific risk factor algorithms (National Cholesterol Education Program Expert Panel, 2001; Ridker et al., 2007). As a result, TGD populations are subject to miscalculation of risk for cardiovascular disease (Poteat et al., 2023).

Clinical Management and Gender-Affirming Care

WPATH recommends taking detailed histories to assess for traditional cardiovascular and cerebrovascular risk factors, along with past and present hormone use and presence or absence of gonads, to tailor management of cardiovascular health (Coleman et al., 2022). Given that masculinizing GAHT (testosterone) may exacerbate hypertension, sleep apnea, and polycythemia (an excess of red blood cells that reduces blood flow), monitoring of blood pressure and lipid profiles is important; changes may require medications and/or alterations in diet to reduce risk (Coleman et al., 2022). As with cisgender people who use hormone therapy, GAHT may alter the lipid profile of TGD people, particularly transgender men, with important implications for cholesterol and cardiovascular health; changes in lipid profile among transgender women are less well understood (Nokoff et al., 2020; Streed et al., 2021).

Feminizing hormone therapy (estrogen) carries an increased risk of thromboembolism (Khan et al., 2019), as described further in Chapter 5 of this report, but changes can be made to counteract this risk. Modifiable risk factors include smoking, obesity, and sedentariness. If there are nonmodifiable risk factors, a transdermal formulation of estrogen is available; use of anticoagulants is also recommended based on limited data (Coleman et al., 2022; Defreyne et al., 2019).

Research Limitations and Gaps

The impact of GAHT on heart disease risk is unknown (Safer, 2021). There are no prospective cohorts of TGD people (other than STRONG) for whom cardiovascular conditions are tracked. One systematic review found only retrospective studies, and those were all conducted in Europe (Defreyne et al., 2019). For better understanding of cardiovascular conditions in TGD populations, as for other chronic conditions, prospective cohorts with sufficient sample sizes of TGD people need to be studied.

Metabolic and Endocrine Disorders

In a systematic review by Rich and colleagues (2020), metabolic and endocrine disorders accounted for 22 percent of the included studies and 6 percent of the data points; studies reported mainly on obesity, diabetes, polycystic ovarian syndrome, and metabolic syndrome.

Prevalence

Rich and colleagues (2020) report that the prevalence of diabetes was as low as <1 percent to as high as 6 percent in studies relying on self-report (vs. 30.2 percent in cisgender patients). The TGD Medicare cohort study found diabetes in 27–31 percent of Medicare clinical diagnoses among TGD beneficiaries (Dragon et al., 2017). The VHA TGD cohort study also found higher odds of type 2 diabetes among that cohort compared with cisgender veterans (aOR 1.34; 95% CI 1.23–1.45) (Brown and Jones, 2016). In contrast, the California Health Interview Survey (2015–2016) found no statistically significant difference in diabetes prevalence between TGD and cisgender people (Herman et al., 2017), and a recent analysis of data from the All of Us Research Program found slightly lower prevelance of diabetes among TGD populations (Tran et al., 2023). Another systematic review showed no increased odds of diabetes in one included study and higher prevalence in another, but the diagnoses were made before the initiation of GAHT; the authors of the review hypothesize that diabetes prevalence may be higher in the latter study partly because TGD people are more likely to be screened in the process of receiving gender-affirming care, and this finding may not represent a true disparity (Defreyne et al., 2019; Wesp, 2016).

Questions about diabetes prevalence can best be answered in prospective cohort studies: in the STRONG cohort study, at baseline, 5.3 percent of transgender male and 9.0 percent of transgender female participants had type 2 diabetes (Quinn et al., 2017). After 9 years of follow-up of 2,869 transgender female and 2,133 transgender male patients, review of medical records revealed that the transgender female cohort had higher prevalence (OR 1.3; 95% CI 1.1–1.5) and incidence of type 2 diabetes (OR 1.4 95% CI 1.1–1.8). There was no significant difference between transgender and cisgender male patients (Islam et al., 2022).

Studies have shown an increased prevalence of type 1 diabetes in TGD children and adults (Defreyne et al., 2017; Logel et al., 2020). One study indicates that TGD youth have increased risk of developing type 1 diabetes, and its authors hypothesize that this is due to minority stress. In that study, 9.9/1,000 U.S. TGD youth had diabetes versus 1.93/1,000 cisgender youth (Maru et al., 2021).

Like the diabetes research, data on obesity are mixed. In the TGD Medicare cohort, TGD patients had a higher prevalence of obesity diagnosis compared with cisgender patients—31.3 percent versus 17.2 percent, respectively (Dragon et al., 2017). Likewise, in the VHA TGD cohort, TGD veterans had higher odds of obesity relative to cisgender controls (aOR 1.58; 95% CI 1.48–1.70) (Brown and Jones, 2016). On the other hand, a systematic review found that TGD people on GAHT were not more likely to be obese compared with age-matched cisgender controls (Defreyne et al., 2019).

Risk and Protective Factors

Risk factors for overweight TGD people include socioeconomic barriers to health care access; disparities in healthy behaviors (e.g., less exercise, perhaps due to lack of safe access to gyms and locker rooms); comorbid physical and mental health conditions; and gender minority stress (Taormina and Iwamoto, 2023). Polycystic ovarian syndrome (PCOS) is a risk factor for developing type 2 diabetes, but the prevalence of PCOS among transgender men is not well known. Two studies included in a review by Rich and colleagues (2020) found an estimated prevalence in transgender men of 32–26 percent, but neither study was based on U.S. populations (Baba et al., 2011; Becerra-Fernandez et al., 2014).

Assessments

Testing for (pre)diabetes includes measuring hemoglobin A1C, which does not differ by sex, and no concerns have been reported about the appropriateness of the test for TGD populations. However, BMI is often used to assess overweight and obesity, and it is unclear which sex standard, if any, should be applied to TGD people (AMA, 2023). Some surgeons place restrictions on BMI before gender-affirming surgery, but this practice is not evidence based (Taormina and Iwamoto, 2023).

Clinical Management and Gender-Affirming Care

The UCSF guidelines state that providers should monitor fasting glucose and hemoglobin A1C when initiating or adjusting hormone therapy (Wesp, 2016). WPATH and the Endocrine Society recommend that preexisting conditions, including diabetes, be “reasonably well controlled” before GAHT is initiated (Coleman et al., 2022; Hembree et al., 2017). UCSF notes that starting GAHT may help patients better control their diabetes. The UCSF guidelines advise that diabetes management be the same for TGD as for cisgender people, regardless of GAHT use (Wesp, 2016). Similarly, USCF prefers that patients with diabetes seeking gender-affirming surgery have normal glucose, but abnormal glucose is not a contraindication for surgery (Wesp, 2016).

Research Limitations and Gaps

The effects of GAHT on diabetes risk is unknown, including in youth using gonadotropin-releasing hormone (GnRH) agonists (medications to delay puberty, as discussed in Chapter 5); little evidence is available on this subject, and what is available is mixed (Islam et al., 2022). The management of diabetes in TGD people has not yet been studied, and UCSF’s

guidelines are the only ones to address this overlap (Moverley et al., 2021; Wesp, 2016). PCOS is a known risk factor for insulin resistance and type 2 diabetes in cisgender women, but impacts in transgender men are unknown (Moverley et al., 2021; Wesp, 2016). Additionally, evidence is lacking on trans-oriented weight loss programs, medications, and bariatric surgeries (Taormina and Iwamoto, 2023).

Chronic Liver Disease

Prevalence

Very little data on chronic liver disease are available. The systematic review by Rich and colleagues (2020) reports that liver outcomes constituted the lowest proportion of available studies examining health among TGD people. However, some research does exist. In the TGD Medicare cohort, TGD beneficiaries fared worse than cisgender beneficiaries with regard to measures of liver disease: 8.6 percent of TGD beneficiaries had a diagnosis of hepatitis, compared with 1.7 percent of cisgender beneficiaries (Dragon et al., 2017). In the same study, the prevalence of nonhepatitis liver conditions was also high in TGD beneficiaries—12 percent compared with 7.3 percent in cisgender beneficiaries (Dragon et al., 2017). On the other hand, the VHA TGD cohort study found that cirrhosis of the liver was less common in TGD than in cisgender veterans (aOR 0.77; 95% CI 0.61–0.96) (Brown and Jones, 2016). Other systematic reviews on transgender health do not report on liver disparities and outcomes (Scheim et al., 2022), and more research is needed in this area.

Risk and Protective Factors

For TGD populations, how GAHT may impact the liver is unknown. Increased substance use (as described above) and lower levels of physical activity among TGD people may contribute to poor liver function; however, there is no empirical evidence to support or refute this hypothesis (Streed at al., 2021). Barriers to adopting liver-healthy behaviors may be challenging to overcome for TGD people. Exercise, for example, may be more challenging because of discomfort with the body; socioeconomic status; mental health issues, such as depression; and lack of safe access to sports teams, sport facilities, and locker rooms.

Assessments

The Model for End-Stage Liver Disease calculation was recently updated to version 3, which added “female sex” as a variable (Newman et al., 2023).

Previously, sex had not been factored into the calculation. The implications of this change for TGD people with chronic liver disease have not yet been studied (Newman et al., 2023). As for other sex-specific measures described in this report, which sex marker to use for TGD people, including those receiving hormone therapy, is unclear. As with other sex-based guidelines, it is possible that a combination of sex and gender identity will lead to a more accurate interpretation; but again, this possibility is untested and unknown.

Clinical Management and Gender-Affirming Care

There are sex-based differences in nonalcoholic fatty liver disease, and estrogen affects metabolic states and hepatic adenomas. Whether GAHT affects liver outcomes is unknown, however (Newman et al., 2023). Among the major transgender standards of care, only the Callen-Lorde Community Health Center (2018) guidelines address management of liver disease. These guidelines direct that liver function be tested regularly if the patient has a self-limited hepatic infection, such as acute hepatitis A and B, and advise waiting to initiate hormone therapy until the patient has recovered and transaminase levels are normalized. Hepatitis C should be treated the same for TGD and cisgender people. For chronic liver disease, Callen-Lorde (2018) recommends that the primary care provider ensure that all relevant vaccinations are up to date and encourage behavioral interventions to minimize further risk.

Research Limitations and Gaps

Virtually nothing is known about chronic liver disease in TGD populations except that it may be more prevalent than in cisgender populations. Data on GAHT management in the context of liver transplantation are needed; there is risk of thromboembolism in the postoperative period, but stopping GAHT has to be weighed against risks of gender dysphoria and mental health sequalae (Newman et al., 2023). Newman and colleagues (2023) recommend prospective research with biobank specimens before and after GAHT initiation to generate data on impacts on the liver.

CO-OCCURING CONDITIONS AND MULTIMORBIDITY

As alluded to throughout this chapter, TGD people are at higher risk than cisgender people of experiencing multimorbidities of both mental and physical health outcomes via syndemics. The term “syndemic” denotes the overlapping, mutually reinforcing combination of two or more diseases or other conditions in a population, especially when caused and reinforced by social inequities and power imbalance (Poteat et al., 2016). The term

has been used to describe the synergistic co-occurrence of substance abuse, mental health conditions, HIV, sexually transmitted infections, violence, racism, poverty, and daily trauma experienced by many TGD people (Poteat et al., 2016).

Analysis of data from the Behavioral Risk Factor Surveillance System indicates that participants in all transgender subgroups experienced worse mental and physical health compared with cisgender participants, while gender nonbinary participants had higher odds of multiple chronic conditions, and poor quality of life compared with both binary transgender and all cisgender participants (Downing and Przedworski, 2018). Another analysis of the same data set found that 36.7 percent of transgender women, 33.8 percent of transgender men, and 40.9 percent of nonbinary participants had two or more chronic health conditions; these participants were also highly likely to be unemployed: aOR 2.39; 95% CI 1.73–3.31). Many participants also had three or more health problems or impairments (transgender women 15 percent, transgender men 17 percent, and nonbinary people 21 percent), and they had much higher odds of not working (aOR 5.18; 95% CI 2.92–9.19) (Cicero et al., 2020). These results are corroborated by Abramovich and colleagues (2020), who found comorbid chronic health conditions were higher among the TGD population studied compared with cisgender controls (702 [33.7%] vs. 2,941 [28.2%]; p < .001.

In another study, older nonbinary adults and transgender women were found to be less likely to have a personal doctor or to have had a checkup in the past 2 years. Older nonbinary adults were also more likely than cisgender controls to have poor mental and physical health, depression, and asthma (Pharr, 2021).

The Amsterdam Cohort of Gender Dysphoria Study reported on all-cause mortality over 5 decades of follow-up. The statistics and causes of death are telling: transgender women were 80 percent and transgender men 280 percent more likely to die compared with cisgender men and cisgender women, respectively (standardized mortality ratio [SMR] 1.8; 95% CI 1.6–2.0, and 2.8; 95% CI 2.5–3.1, respectively). Their top causes of death were cardiovascular disease, lung cancer, HIV, and suicide. Transgender men were 80 percent more likely to die compared with cisgender women (SMR 1.8; 95% CI 1.3–2.4); their top causes of death were nonnatural causes (e.g., suicide). Over the 5 decades of follow-up, mortality risk did not decrease for TGD people (de Blok et al., 2021).

From disparities in the burden of chronic physical conditions and risk (e.g., cardiovascular disease, HIV) to disparities in the burden of mental health conditions (e.g., depression, anxiety), multiple studies demonstrate how multilevel stigma and structural factors (e.g., antitransgender policies, practices, and laws)—which could be addressed by interventions—contribute to the disproportionate burden of disease for TGD people (Bockting et al.,

2013; Brown and Jones, 2016; Caceres et al., 2020; Feldman et al., 2021; Poteat et al., 2016; Streed et al., 2021; Stutterheim et al., 2021; Tebbe and Budge, 2022; White Hughto et al., 2015), and may cause or contribute to chronic disease morbidity over the life course.

Along with growing recognition of the magnitude and breadth of health inequities facing TGD people, an emerging health literature addresses resilience at the TGD individual and community levels (Edwards et al., 2020; McCann and Brown, 2017; Tankersley et al., 2021). Resilience, which includes coping skills, strategies, and social support systems that help mitigate adversity, is a key consideration for TGD health and wellbeing (Bockting et al., 2020; Puckett et al., 2024; Reisner et al., 2016a). Importantly, resilience as an individual-level solution to structural drivers of inequity has been critiqued as inappropriate and inadequate (Suslovic and Lett, 2023). Instead, addressing structural barriers to TGD health through systems-level changes more closely matches the solution to the problem and better promotes health equity.

When considering the disproportionate burden of chronic disease experienced by TGD people, it is essential to identify the fundamental causes of these disparities (Link and Phelan, 1995, 2001; Williams et al., 2019). As noted, a growing body of evidence indicates that stigma and discrimination, including harmful laws and practices, drive health inequities in TGD populations (Caceres et al., 2020; Dragon et al., 2017; Meyer et al., 2017; Reisner et al., 2016b; Streed et al., 2021; White Hughto et al., 2015). Several key concepts, models, and frameworks have been used to advance an understanding of how stigma and discrimination, at multiple levels and across multiple minoritized identities, lead to health inequities across the life course (Crenshaw, 1991; Homan et al., 2021; Smith et al., 2022; Wesp et al., 2019). Table 6-7 provides brief definitions of salient concepts for TGD populations.

SUMMARY OF KEY POINTS

This chapter has examined a range of co-occurring conditions that may be common among TGD people, presenting data on the high co-occurrence of several conditions, including various mental health conditions, ASD, and HIV. Other important co-occurring conditions are described throughout this report, including cancers, osteoporosis, fertility, respiratory disorders, and chronic kidney disease. Taken together, this evidence shows that TGD people have a disproportionate level of co-occurring chronic diseases and mental health conditions. These significant health concerns do not occur in a vacuum: multilevel stigma and structural factors shape the disproportionate burden of disease in TGD people, potentially putting them at greater risk of disease with reduced ability to seek the services they need for

TABLE 6-7 Conceptual Frameworks and Explanatory Models Salient for Health for Transgender and Gender Diverse People

SOURCES: Bockting et al., 2013; Boulware et al., 2003; Bowleg, 2012, 2019, 2021; Corbie-Smith et al., 2002; D’Avanzo et al., 2019; Dubois, 2012; DuBois and Juster, 2022; Geronimus et al., 2006; Homan et al., 2021; Jaiswal and Halkitis, 2019; Krieger, 1994, 2016; LaVeist et al., 2009; Lett et al., 2023; Link and Phelan, 2001; McEwen, 2000; Mohottige and Boulware, 2020; OASH, n.d.; Perez-Brumer et al., 2021; Richman and Zucker, 2019; Smart et al., 2022; Smith et al., 2022; Valdiserri et al., 2019; Wesp et al., 2019.

optimal care and management. These realities may lead to delayed diagnosis and poorer outcomes for TGD people with chronic disease.

While the co-occurring conditions described in this chapter were not among the specific conditions reviewed by the committee (i.e., respiratory disease, growth failure, chronic kidney disease, reproductive cancers, and HIV), the committee notes parallels between the conditions described in this chapter and those described in Part III of this report, including notable disparities and important considerations for appropriate assessment and clinical management of TGD people with chronic disease.

Given that many of the conditions described here are categories within the Social Security Administration’s (SSA’s) Listings, the committee presents these data to inform SSA on how TGD people may experience various chronic health conditions that are important for disability evaluation, particularly when TGD applicants present with more than one such condition. Importantly, as discussed in Chapter 1, under SSA’s disability determination process, SSA considers the combined effects of all physical and mental conditions (“impairments”) when determining eligibility for benefits (SSA, 2017).⁴ Two-thirds of all SSA disability beneficiaries report physical or mental health impairments in more than one impairment category, and beneficiaries with multiple impairments tend to have poorer health and more activity limitations than beneficiaries with one impairment (Walker and Roessel, 2019). Although available SSA data do not allow for analysis of impairments among TGD beneficiaries, given the body of evidence presented in this chapter that TGD people often experience physical and mental health

___________________

⁴ 20 C.F.R. § 404.1523 (2017).

conditions at a higher rate than the cisgender population, TGD people may be particularly likely to present to SSA with multiple impairments.

Finally, as presented in this chapter, there is a great need for TGD health research outside of mental and sexual health. Data are lacking on nearly every chronic condition and across the lifespan. Age-related chronic conditions among aging TGD people need to be understood. Likewise, long-term impacts will unfold as more TGD people transition at younger ages and more TGD youth will have had a history of GnRH agonist use. Rigorous, prospective cohort studies that collect biospecimens and survey data before GnRH agonist and GAHT use and at regular intervals thereafter are key to establishing temporality and causation for a variety of conditions. Representative, probability-based samples are also important; to this end, more large and national studies need to include appropriate, sensitive, and standardized measures that capture both gender identity and sex recorded at birth. The field of transgender health needs more studies based on patient-centered outcomes and on research questions the community deems important.

REFERENCES

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