Transgender people in the United States (US) experience significant health disparities throughout their life course relative to cisgender (non-transgender) people (1–6). These disparities stem from multilevel sources of stigma that serve as sources of chronic stress as well as barriers to accessing essential resources such as healthcare, employment, and income (7–9). While extensive community-based research drawn from convenience samples (10, 11), and research using state or national data has assessed the health of transgender youth and adults overall (12–14) and relative to cisgender people (15–18), a dearth of national studies have compared the health of an exclusively aging (i.e., age 65 or older) sample of transgender and cisgender adults.

The risk of being diagnosed with a chronic health condition, such as cancer, HIV, depression, osteoporosis, and dementia, increases as one ages (19, 20). Aging transgender adults are expected to be at an even higher risk of developing physical and mental health conditions than their cisgender peers due to stigma-related stress experienced throughout their lives and barriers to accessing quality healthcare (9, 21–25). Although researchers are increasingly studying the health of aging transgender adults (26–28), and some national studies have explored disparities among predominantly aging populations relative to cisgender groups (29–32), no national research, to our knowledge, has explored within- (e.g., trans feminine people vs. trans masculine people) and between- (e.g., transgender vs. cisgender) group gender differences among aging transgender adults and a general population of cisgender adults. Without comparative data on the health of aging transgender and cisgender subpopulations, it is difficult to know which subgroups are in greatest need of public health and policy interventions.

Recent methodological advances have enabled the use of claims databases to study the health of transgender populations. Blosnich et al. (2013) innovatively used transgender-specific International Classification of Diseases, Ninth Edition (ICD-9) diagnosis codes (e.g., Gender Identity Disorder (GID)) to identify transgender veterans using national Veteran Health Administration data (14). Proctor and colleagues later followed by applying transgender-related ICD-9 diagnosis codes to identify age- and disability-entitled transgender Medicare beneficiaries (33). Using the same approach as Proctor et al., Dragon and colleagues found that, compared to cisgender Medicare recipients receiving care in 2015, a higher proportion of transgender beneficiaries receiving care during the sample year had been diagnosed with several major health conditions, including asthma, autism spectrum disorder, chronic obstructive pulmonary disease, depression, hepatitis, HIV, schizophrenia, and substance use disorders (30). Building on the work of Proctor and Dragon, Progovac and colleagues examined disparities between transgender and cisgender Medicare beneficiaries receiving care between 2009 and 2014 (31). They found that older and disabled transgender Medicare beneficiaries had more diagnoses for chronic health conditions than their cisgender counterparts (31). Notably, however, none of these studies examined health diagnoses disparities by gender subgroup (trans feminine, trans masculine, cisgender male, cisgender female), despite prior survey-based research showing substantial within and between gender group variations in mental and physical health conditions (2, 6, 10, 11, 34, 35).

Our team has advanced algorithms identifying transgender beneficiaries in claims data and inferring their gender (12, 13, 36). Using commercial insurance data from 2001-2019, we adapted a method developed by Jasuja and colleagues (13) that used diagnosis, procedure, and pharmacy claim codes to identify individuals with one or more transgender-related diagnoses or Endocrine Disorder Not Otherwise Specified [Endocrine NOS] in conjunction with prescriptions for gender-affirming hormones (e.g., estrogen, testosterone) or gender-affirming procedures (e.g., phalloplasty, vaginoplasty) to identify 38,598 transgender adults. We furthered the algorithm using an approach developed by Yee, Lind, & Downing (36) for Oregon Medicaid recipients to improve our ability to categorize transgender samples by inferred gender. ¹ Specifically, we used a hierarchical approach to examine beneficiaries’ history of gender-affirming and reproductive anatomy-specific ² procedures (e.g., prostate-related procedures, hysterectomy), diagnoses, and pharmacy claims for gender-affirming hormones to categorize the sample based on inferred gender identity: ³ trans masculine/nonbinary (TMN) or trans feminine/nonbinary (TFN) (12). ⁴ By including reproductive anatomy-specific procedures and diagnoses in combination with gender-affirming care, we were able to infer the gender of 76% of the sample (50% TMN; 26% TFN), which represented a notable improvement from prior approaches (13).

When we applied our modified algorithm to study the health of younger, commercially-insured transgender individuals (12), we found that relative to TMN people, TFN people had significantly higher predicted probabilities of most health condition diagnoses, including HIV, atherosclerotic cardiovascular disorder, myocardial infarction, alcohol use disorder, and substance use disorder (4). In contrast, TMN individuals had significantly higher predicted probabilities of diagnosed post-traumatic stress disorder and depression than TFN people. While our prior research provides insights into within-group gender-related disparities in health diagnoses among commercially-insured adults aged 18 and over, it is unknown whether these patterns are similar among aging transgender adults aged 65 and older. To more fully understand the health of aging transgender adults, research is needed to explore within- and between-group gender differences in health diagnoses among aging transgender adults, overall and relative to their cisgender counterparts. As the largest insurer of U.S adults aged 65 and older (37), Medicare is the ideal data source to utilize to document within- and between-group disparities in health diagnoses for aging transgender and cisgender adults.

Building on prior work (13, 31, 36), in the present study, we sought to apply our claims-based method (12) to identify transgender and cisgender samples in Medicare data, stratify the samples by gender, and explore within- and between-group gender differences in health diagnoses among aging transgender and cisgender Medicare beneficiaries. Findings from this national study can help identify health diagnosis disparities among aging Medicare beneficiaries and the subgroups in greatest need of tailored interventions to prevent and treat adverse health outcomes.

This study advances the fields of endocrinology and population health research through the application of an algorithm that identifies transgender people in Medicare data and stratifies by inferred gender to explore within- and between-group disparities in health diagnoses among aging transgender and cisgender beneficiaries. We found that overall, aging TFN or TMN Medicare beneficiaries had a significantly higher probability of every health diagnosis studied relative to cisgender male or female beneficiaries, with TFN individuals experiencing some of the highest diagnosis burdens relative to other groups. Future application of these methods will enable the study of rare and hormone and anatomy-related conditions among hard-to-reach aging transgender populations and their cisgender counterparts and can inform interventions to address documented health diagnosis disparities (39).

In understanding the health diagnosis disparities observed here, it is essential to underscore the role of stigma and its stress-related sequelae that transgender individuals differentially experience throughout their lives relative to cisgender individuals (7). Indeed, at the structural level, harmful state, federal, and organizational policies may intentionally or unintentionally restrict access to the essential resources (e.g., healthcare, education, employment, housing, public bathrooms, and other accommodations) that transgender people need to maintain their health (7). Additionally, exposure to interpersonal discrimination, violence, and other sources of enacted stigma at the hands of healthcare providers, family members, employers, educators, sexual partners, and others further restricts access to essential resources and contributes to poor health directly and indirectly through chronic stress (7). As a person ages, chronic activation of the body’s stress response system can compromise health over time via a process called allostatic load (40–42). Chronic stress is associated with adverse health outcomes, such as cancer, hypertension, diabetes, mood and substance use disorders, and even death (43, 44), and is therefore theorized to be a primary driver of the health diagnosis disparities observed among aging transgender individuals relative to cisgender individuals in this study (7).

Few large-scale studies have explored disparities within transgender populations, and relative to cisgender males and females for health conditions such as breast cancer that are known to differ by assigned birth sex. In the United States, breast cancer is approximately 70-100 times less common among cisgender males than females (45). Building on prior cancer research with transgender samples (46–50), we found that both TMN people and cisgender females had a significantly elevated probability of a breast cancer diagnosis relative to TFN people and cisgender males. Additionally, although the probability of a breast cancer diagnosis in TFN people was significantly lower than that of cisgender females, it was significantly higher relative to that of cisgender males – a finding that aligns with data from a younger Dutch cohort study comparing the incidence of breast cancer in TFN people on estrogen to cisgender females and males (46). Lifetime stress, a risk factor for cancer (51, 52), together with higher rates of screening among transgender people with breast tissue (53), may have contributed to the elevated probability of being diagnosed with breast cancer among TFN and TMN people relative to their cisgender counterparts. Higher levels of endogenous estradiol in the blood are also associated with a higher risk of breast cancer (54), whereas endogenous androgens are known to inhibit the progression of certain types of breast cancer (46, 55). Decreased testosterone due to the use of antiandrogenic treatment and orchiectomy and denser breast tissue due to the use of exogenous hormones (56) could increase the risk for certain types of breast cancer in TFN people relative to cisgender males (46, 55). Still, the risk of taking exogenous estrogen for gender affirmation is no greater for TFN people than it is for cisgender females taking such therapies for other indications (57–59). Moreover, our study found a significantly lower probability of being diagnosed with breast cancer in TFN people as compared to cisgender females, which may be due to TFN people having less breast tissue and lower lifetime exposure to estrogen than cisgender females.

Notable differences in the probability of osteoporosis and arthritis were also observed among TFN and TMN individuals relative to their cisgender comparators. Specifically, TMN individuals had the highest probability of being diagnosed with osteoporosis and arthritis than all other groups. Further, although the probability of an osteoporosis diagnosis was substantially and significantly lower among TFN people than cisgender females, TFN people had a significantly higher probability of having an osteoporosis diagnosis relative to cisgender males. Our findings align with research showing that osteoporosis and most types of arthritis are more prevalent in older people assigned a female sex at birth than those assigned a male sex at birth (60–62). Obesity, heart disease, and smoking can also increase the risk for rheumatoid arthritis (60, 63), and our study and prior research suggest that TMN people may be at elevated risk of being diagnosed with these conditions (3, 64–66). Relatedly, known risk factors for osteoporosis in the general population include high alcohol consumption, tobacco use, anorexia nervosa, rheumatoid arthritis, chronic kidney disease, and HIV infection (59, 62, 67–69), all of which (except anorexia, which was not studied) were more commonly diagnosed among TFN or TMN people in our sample relative to cisgender males and females. Low physical activity has also been linked to osteoporosis risk in cisgender people (62) and transgender people, even before initiating hormones (59). Research finds that some TFN and TMN individuals have lower levels of physical activity than their cisgender comparators due to various social and physical barriers to exercising, including inadequate changing facilities, revealing and heavily gendered sports clothing, body dissatisfaction, and fears of acceptance (70–72). Additionally, stress is a major risk factor for osteoporosis (62), and other chronic conditions (e.g., tobacco smoking) that increase osteoporosis and arthritis risk (61, 62, 73); and as previously noted, transgender individuals experience greater stigma-related stress throughout their lives relative to cisgender people (7).

Wear and tear on one’s joints and changes in hormone levels in older age are associated with a greater risk of arthritis and osteoporosis, respectively (62, 74, 75). Although there is no evidence to suggest a causal link between exogenous hormone use and arthritis risk in transgender people, in considering osteoporosis risk, the World Professional Association of Transgender Health notes that the use of gender-affirming medical and surgical interventions, such as hormone therapy, androgen blockade, and gonadectomy, have the potential to influence bone health in different ways (59). While testosterone therapy has been associated with no change or even improvements in bone density among TMN people (59, 67, 76), the higher probability of being diagnosed with osteoporosis among TMN people in this sample may be due to natural reductions in estrogen among those who experienced menopause (62, 75). Further, although TFN people have been shown to have improved bone density after initiating estrogen (59, 67, 77, 78), risk factors for osteoporosis include the absence of or underutilization of estrogen after gonadectomy or the use of androgen blockers without or with insufficient estrogen (59, 67, 79). Further, although Gonadotropin-Releasing Hormone Agonists (GnRHa) are very effective in reducing testosterone levels to help TFN individuals achieve their gender-affirmation goals, the use of GnRHA can result in osteoporosis if concurrent doses of estrogen are insufficient (59, 67, 80). In light of prior research, our findings underscore the necessity for clinicians to understand the various physiological, developmental, behavioral, and environmental risk and protective factors for osteoporosis and other health conditions in order to support aging transgender and cisgender individuals in optimizing their health and well-being.

When exploring mental health, in alignment with prior research (5, 12, 13, 30, 59, 81), this study found a significantly higher probability of all mental health diagnoses among both aging TFN and TMN Medicare beneficiaries relative to their cisgender counterparts. Although TFN and TMN people had a similar probability of having a dementia diagnosis, the probability among TFN and TMN people was significantly elevated relative to cisgender males and females. Further, although depression diagnoses were also significantly elevated among TFN and TMN people compared to the cisgender subgroups, both TMN people and cisgender females had a significantly higher probability of depression than TFN people and cisgender males, respectively. Prior research finds that individuals assigned a female sex at birth are twice as likely to be diagnosed with depression than people assigned a male sex at birth (82, 83), which is consistent with our findings. Burgeoning research also finds an elevated probability of Alzheimer’s disease and related dementias (84) and schizophrenia (85) diagnoses among transgender people relative to cisgender individuals. Although the mechanisms underlying these disparities are not well understood, misdiagnoses by untrained or biased providers may contribute to more diagnoses for transgender people, particularly in the case of schizophrenia (59, 60). Additionally, transgender people have historically been required to undergo psychotherapy to be approved for medical gender affirmation treatment (86–88); thus, the higher probability of mental health diagnoses observed here may be due to increased contact with mental health specialists rather than a reflection of the true probability of these conditions in aging transgender populations (85). Nonetheless, extensive research has documented disparities in poor mental health among transgender vs. cisgender individuals (2, 59, 89). Given that the onset of depression, dementia, cognitive decline, and schizophrenia have all been linked to stress in both transgender and cisgender samples (7, 90–96), it is quite probable that the elevated mental health burden observed among aging transgender people in this sample is due to the high levels of stigma-related stress that transgender people experience throughout the life course including in the context of receiving medical care (7, 26, 97).

Some of the most striking within- and between- gender group diagnostic disparities were observed with regard to infectious diseases. The probability of HIV/AIDS among TFN people was approximately 9-fold that of TMN people and cisgender females and 4.5-fold that of cisgender males. The high probability of HIV/AIDS among TFN people is well documented in the literature (4, 12, 13, 98) and has been attributed to multilevel factors. For example, TFN people may acquire HIV at higher rates due to networks-level factors such as the high prevalence of HIV within TFN people’s limited pool of potential sexual partners or anatomical considerations that predispose TFN people with a penis to engage in sexual acts that carry greater HIV risk (i.e., receptive anal sex) (99, 100). A confluence of stigma-related, structural, and interpersonal factors also restrict access to essential human needs (i.e., employment, shelter, food, love, gender affirmation) for TFN people (7) and can lead to engagement in HIV risk behavior such as transactional sex for financial survival (99, 100), receptive anal sex (i.e., “bottoming”) as a means to be affirmed in one’s gender when access to other sources of affirmation are limited (100–102), and condomless sex to please one’s sexual partner in the context of relationship stigma and partner scarcity (100, 103, 104). Similarly, the probability of hepatitis was significantly higher among TFN people than all other groups, and the probability of a hepatitis diagnosis among TMN people was roughly twice that of cisgender males and females. In addition to the aforementioned sexual pathways, the significantly higher probability of a hepatitis diagnosis among transgender people relative to cisgender individuals may also be driven by the sharing of syringes for injecting drugs, hormones, and silicone - behaviors that may be more prevalent among transgender people due to stigma-related barriers to healthcare (7, 99–101, 105–107).

Consistent with prior research with Medicare- and commercially-insured individuals (3, 4, 12, 13, 30), aging transgender Medicare beneficiaries in this sample had a significantly higher probability of most substance use disorder diagnoses than their cisgender comparators. Research has consistently found elevated levels of substance use and diagnosed substance use disorders among transgender samples relative to cisgender samples (3, 5, 12, 13, 30, 108), due in part to the need to cope with the psychological toll of discrimination, violence, and other forms of stigma (1, 7, 34, 109). In prior studies of younger, commercially-insured transgender individuals (3, 4, 12, 13), drug, alcohol, and tobacco use disorder diagnoses were particularly elevated among TFN people than TMN people. In contrast, the probability of having a drug use disorder diagnosis was fairly comparable between TFN and TMN people in the current study, though the probability of alcohol and tobacco use disorder diagnoses was significantly elevated among TFN people relative to TMN people in the sample. A similar trend was observed for cisgender individuals, such that cisgender males had a significantly higher probability of alcohol and tobacco use disorder diagnoses than cisgender females. The substance use disorder findings suggest that although stigma likely drives the higher prevalence of substance use disorders observed among transgender people (7), individuals assigned a male sex at birth may be more susceptible to some substance use disorders than those assigned a female sex at birth (110, 111). It is also possible that developmental factors may lead individuals assigned a male sex at birth to cope with stress using certain substances more frequently than those assigned a female sex at birth (110, 111). Although the receipt of a diagnosis is an important step in linkage to treatment, research finds that transgender people face difficulty finding affirming substance use treatment services (112–114). Thus, efforts are needed to effectively prevent and treat substance use disorders among transgender people by reducing societal stigma (7), helping transgender people to cope with stigma through health-promoting means (115, 116), and improving access to gender-affirming substance use treatment services (117).

We adapted prior algorithms (3, 13, 33) to identify a large sample of aging transgender Medicare beneficiaries and examine within- and between-group differences in health diagnoses among transgender people and their cisgender counterparts. Extending prior research (3, 5, 12, 13, 30, 31, 33), we observed an elevated burden of health condition diagnoses among TFN or TMN people overall, with the greatest burden observed among TFN people relative to other groups. Our novel methods to identify a transgender sample using Medicare claims data and infer gender may be helpful for future researchers seeking to study the diagnosis of rare conditions, as well as identify transgender subgroups in need of preventive and treatment interventions aimed at reducing morbidity (26, 29, 30, 32) and mortality (42, 121) among aging transgender people in the U.S.

The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.

This study was approved by the Brown University Institutional Review Board. Written informed consent from the participants was not required to participate in this study in accordance with national legislation and institutional requirements.

JH and TS conceived the project and wrote the grants that funded access to the data and supported the analyst's time. JH, TS, AA, JE, LH, KY, and JD were involved in developing the methods to identify the transgender sample and stratify the sample by inferred gender. All authors were involved in refining the algorithm. JH wrote and edited the manuscript and designed and edited the tables and supplementary figures. HV conducted the analyses and populated the tables. KY and LH reviewed the statistical code. GB contributed to the writing of the introduction and formatting of the paper. KY created Figure 1 . All authors contributed to the article and approved the submitted version.