Non-affirmation minority stress, internalized transphobia, and subjective cognitive decline among transgender and gender diverse veterans aged 45 years and older.

OBJECTIVES: To examine the associations of two measures of minority stress, non-affirmation minority stress and internalized transphobia, with subjective cognitive decline (SCD) among transgender and gender diverse (TGD) veterans. METHOD: We administered a cross-sectional survey from September 2022 to July 2023 to TGD veterans. The final analytic sample included 3,152 TGD veterans aged ≥45 years. We used a generalized linear model with quasi-Poisson distribution to calculate prevalence ratios (PR) and 95% confidence intervals (CIs) measuring the relationship between non-affirmation minority stress and internalized transphobia and past-year SCD. RESULTS: The mean age was 61.3 years (SD = 9.7) and the majority (70%) identified as trans women or women. Overall, 27.2% (n = 857) reported SCD. Adjusted models revealed that TGD veterans who reported experiencing non-affirmation minority stress or internalized transphobia had greater risk of past-year SCD compared to those who did not report either stressor (aPR: 1.09, 95% CI: 1.04-1.15; aPR: 1.19, 95% CI: 1.12-1.27). CONCLUSION: Our findings demonstrate that proximal and distal processes of stigma are associated with SCD among TGD veterans and underscore the need for addressing multiple types of discrimination. Above all, these results indicate the lasting sequelae of transphobia and need for systemic changes to prioritize the safety and welfare of TGD people.

Barriers and Facilitators to Gender-affirming Hormone Therapy in the Veterans Health Administration.

BACKGROUND: In 2011, the Veterans Health Administration (VHA) established a policy for the delivery of transition-related services, including gender-affirming hormone therapy (GAHT), for transgender and gender diverse (TGD) patients. In the decade since this policy's implementation, limited research has investigated barriers and facilitators of VHA's provision of this evidence-based therapy that can improve life satisfaction among TGD patients. PURPOSE: This study provides a qualitative summary of barriers and facilitators to GAHT at the individual (e.g., knowledge, coping mechanisms), interpersonal (e.g., interactions with other individuals or groups), and structural (e.g., gender norms, policies) levels. METHODS: Transgender and gender diverse patients (n = 30) and VHA healthcare providers (n = 22) completed semi-structured, in-depth interviews in 2019 regarding barriers and facilitators to GAHT access and recommendations for overcoming perceived barriers. Two analysts used content analysis to code and analyze transcribed interview data and employed the Sexual and Gender Minority Health Disparities Research Framework to organize themes into multiple levels. RESULTS: Facilitators included having GAHT offered through primary care or TGD specialty clinics and knowledgeable providers, with patients adding supportive social networks and self-advocacy. Several barriers were identified, including a lack of providers trained or willing to prescribe GAHT, patient dissatisfaction with prescribing practices, and anticipated or enacted stigma. To overcome barriers, participants recommended increasing provider capacity, providing opportunities for continual education, and enhancing communication around VHA policy and training. CONCLUSIONS: Multi-level system improvements within and outside the VHA are needed to ensure equitable and efficient access to GAHT.

Veterans Health Administration (VHA) policy mandates the provision of several gender-affirming health services, including gender-affirming hormone therapy (GAHT). GAHT can improve quality of life among transgender and gender diverse (TGD) patients by more closely aligning their physical self with their internal sense of self. We conducted interviews with 30 TGD patients and 22 VHA healthcare providers to gather their perspectives on barriers and facilitators to GAHT in the VHA. Findings revealed that facilitators of GAHT access included information sharing through social networks and relying on providers in primary care or specialized TGD health clinics for prescribing, while barriers included a shortage of trained providers and patient dissatisfaction with prescribing practices. Anticipating or experiencing stigma from providers and other patients was also identified as a barrier to GAHT. To overcome barriers, participants recommended increasing provider capacity, offering continuous education on GAHT prescribing, and improving communication about VHA policies and training. Comprehensive improvements at various levels, both within and outside the VHA, are necessary to improve access to this important evidence-based treatment for TGD patients.

Gaps in evidence on treatment of male osteoporosis: a Research Agenda.

OBJECTIVE: To identify key research gaps regarding medication therapy to prevent osteoporotic fractures in men. DATA SOURCES: Articles from the peer-reviewed literature containing empirical studies of the use of medication therapy for fracture prevention in men, either in clinical trials or observational studies. STUDY SELECTION AND DATA EXTRACTION: We searched PubMed with search terms including "osteoporosis AND medication therapy management". We read all articles to ensure that they were indeed empirical studies of our topic. For each included study, we searched for all articles in the bibliography, all articles that cited the article, and all related articles, using these functions in PubMed. DATA SYNTHESIS: We have identified six research gaps that could inform the more rational, evidence-based treatment of male osteoporosis. Specifically, among men, we lack key information about: (1) whether treatment can prevent clinical fractures, (2) rates of side effects and complications of therapy, (3) the role of testosterone in treatment, (4) the comparative effectiveness of different therapeutic regimens, (5) role of drug holidays for those receiving bisphosphonates and sequential therapies, and (6) effectiveness of therapy for secondary prevention. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Addressing these six topics should be key goal for the next decade of research on male osteoporosis.

The epidemiology of mild cognitive impairment, Alzheimer's disease and related dementia in U.S. veterans.

INTRODUCTION: US veterans have a unique dementia risk profile that may be evolving over time. METHODS: Age-standardized incidence and prevalence of Alzheimer's disease (AD), AD and related dementias (ADRD), and mild cognitive impairment (MCI) was estimated from electronic health records (EHR) data for all veterans aged 50 years and older receiving Veterans Health Administration (VHA) care from 2000 to 2019. RESULTS: The annual prevalence and incidence of AD declined, as did ADRD incidence. ADRD prevalence increased from 1.07% in 2000 to 1.50% in 2019, primarily due to an increase in the prevalence of dementia not otherwise specified. The prevalence and incidence of MCI increased sharply, especially after 2010. The prevalence and incidence of AD, ADRD, and MCI were highest in the oldest veterans, in female veterans, and in African American and Hispanic veterans. DISCUSSION: We observed 20-year trends of declining prevalence and incidence of AD, increasing prevalence of ADRD, and sharply increasing prevalence and incidence of MCI.

Long-term Psychoactive Medications, Polypharmacy, and Risk of Suicide and Unintended Overdose Death Among Midlife and Older Women Veterans.

BACKGROUND: Rates of suicide and unintended overdose death are high among midlife and older women, yet there is paucity of data identifying women at greatest risk. Psychoactive medications, commonly prescribed and co-prescribed in this population, may serve as salient indicators of risk for these outcomes. OBJECTIVE: To determine whether long-term psychoactive medications and psychoactive polypharmacy predict risk of suicide and unintended overdose death among midlife and older women Veterans above and beyond other recognized factors. DESIGN: Longitudinal cohort study PARTICIPANTS: Women Veterans aged ≥ 50 with at least one Veterans Health Administration (VHA) clinical encounter in FY2012-2013. MAIN MEASURES: Long-term psychoactive medications (opioids, benzodiazepines, sedative-hypnotics, antidepressants, antipsychotics, and antiepileptics, prescribed for ≥ 90/180 days) and psychoactive polypharmacy (overlapping for ≥ 1 day) from VHA pharmacy records; suicide and unintended overdose death through December 31, 2018. KEY RESULTS: In this national sample of 154,558 midlife and older women Veterans (mean age 63.4, SD 9.3 years), 130 died by suicide and 175 died from unintentional overdose over an average of 5.6 years. In fully adjusted models, long-term opioids (hazard ratio (HR) 2.01, 95% CI 1.21-3.35) and benzodiazepines (HR 2.99, 95% CI 1.82-4.91) were associated with death by suicide; opioids (HR 3.62, 95% CI 2.46-5.34), benzodiazepines (HR 2.77, 95% CI 1.73-4.42), sedative-hypnotics (HR 1.87, 95% CI 1.06-3.29), antidepressants (HR 1.47, 95% CI 1.03-2.12), antipsychotics (HR 1.81, 95% CI 1.02-3.22), and antiepileptics (HR 2.17, 95% CI 1.48-3.19) were associated with unintended overdose death. Women who were co-prescribed ≥ 3 psychoactive medications had over 2-fold increased risk of suicide (HR 2.83, 95% CI 1.65-4.84) and unintended overdose death (HR 2.60, 95% CI 1.72-3.94). CONCLUSIONS: Long-term psychoactive medications and psychoactive medication polypharmacy were important indicators of risk for death by suicide and death by unintended overdose among midlife and older women Veterans, even after accounting for psychiatric and substance use disorders.

Validating Data-Driven Methods for Identifying Transgender Individuals in the Veterans Health Administration of the US Department of Veterans Affairs.

We sought to operationalize and validate data-driven approaches for identifying transgender individuals in the Veterans Health Administration (VHA) of the US Department of Veterans Affairs (VA) through a retrospective analysis using VA administrative data from 2006-2018. Besides diagnoses of gender identity disorder (GID), a combination of non-GID data elements was used to identify potentially transgender veterans, including 1) an International Classification of Diseases (Ninth or Tenth Revision) code of endocrine disorder, unspecified or not otherwise specified; 2) receipt of sex hormones not associated with the sex documented in the veteran's records (gender-affirming hormone therapy); and 3) a change in the veteran's administratively recorded sex. Both GID and non-GID data elements were applied to a sample of 13,233,529 veterans utilizing the VHA of the VA between January 2006 and December 2018. We identified 10,769 potentially transgender veterans. Based on a high positive predictive value for GID-coded veterans (83%, 95% confidence interval: 77, 89) versus non-GID-coded veterans (2%, 95% confidence interval: 1, 11) from chart review validation, the final analytical sample comprised only veterans with a GID diagnosis code (n = 9,608). In the absence of self-identified gender identity, findings suggest that relying entirely on GID diagnosis codes is the most reliable approach for identifying transgender individuals in the VHA of the VA.

Menopausal Hormone Therapy and Suicide in a National Sample of Midlife and Older Women Veterans.

BACKGROUND: Among midlife and older women, menopause symptoms and menopausal hormone therapy have been linked to mental health disorders and other comorbidities related to suicide. However, the role of hormone therapy as a prognostic factor of suicide risk is largely unknown. OBJECTIVES: To examine associations between menopausal hormone therapy, suicide attempts, and suicide among midlife and older women Veterans. RESEARCH DESIGN: In this longitudinal analysis of national Veterans Health Administration data from women Veterans aged 50 years and above, we used Fine-Gray proportional hazards models to examine associations between menopausal hormone therapy (prescribed in 2012-2013) and incident suicide attempts and suicide (index date-2016). MEASURES: Menopausal hormone therapy and psychoactive medications from pharmacy records; suicide attempts and suicide from national suicide data repositories; demographic variables, medical and psychiatric diagnoses, and substance use disorders from electronic medical record data and International Classification Diagnoses-9-CM codes. RESULTS: In this national sample of 291,709 women Veterans (mean age 60.47, SD 9.81), 6% were prescribed menopausal hormone therapy at baseline. Over an average of 4.5 years, 2673 had an incident suicide attempt (93%) or death by suicide (7%). Adjusting for age, race, and medical diagnoses, menopausal hormone therapy was associated with increased risk of suicide attempt (hazard ratio 1.41; 95% confidence interval, 1.22-1.64) and over 2-fold increased risk of death by suicide (hazard ratio 2.47; 95% confidence interval, 1.58-3.87). Associations with death by suicide remained significant after accounting for psychiatric comorbidity and psychoactive medications. CONCLUSIONS: Menopausal hormone therapy may be an important indicator of suicide risk among midlife and older women.

Homelessness and Veteran Status in Relation to Nonfatal and Fatal Opioid Overdose in Massachusetts.

BACKGROUND: Compared with non-Veterans, Veterans are at higher risk of experiencing homelessness, which is associated with opioid overdose. OBJECTIVE: To understand how homelessness and Veteran status are related to risks of nonfatal and fatal opioid overdose in Massachusetts. DESIGN: A cross-sectional study. PARTICIPANTS: All residents aged 18 years and older during 2011-2015 in the Massachusetts Department of Public Health's Data Warehouse (Veterans: n=144,263; non-Veterans: n=6,112,340). A total of 40,036 individuals had a record of homelessness, including 1307 Veterans and 38,729 non-Veterans. MAIN MEASURES: The main independent variables were homelessness and Veteran status. Outcomes included nonfatal and fatal opioid overdose. RESULTS: A higher proportion of Veterans with a record of homelessness were older than 45 years (77% vs. 48%), male (80% vs. 62%), or receiving high-dose opioid therapy (23% vs. 15%) compared with non-Veterans. The rates of nonfatal and fatal opioid overdose in Massachusetts were 85 and 16 per 100,000 residents, respectively. Among individuals with a record of homelessness, these rates increased 31-fold to 2609 and 19-fold to 300 per 100,000 residents. Homelessness and Veteran status were independently associated with higher odds of nonfatal and fatal opioid overdose. There was a significant interaction between homelessness and Veteran status in their effects on risk of fatal overdose. CONCLUSIONS: Both homelessness and Veteran status were associated with a higher risk of fatal opioid overdoses. An understanding of health care utilization patterns can help identify treatment access points to improve patient safety among vulnerable individuals both in the Veteran population and among those experiencing homelessness.

Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy.

BACKGROUND: The effect of gender affirming hormone therapy (GAHT) on clinical laboratory parameters, including levels of liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST), is an area of uncertainty in transgender health. AIM: We sought to estimate the distribution parameters of liver enzyme levels among transmasculine (TM) and transfeminine (TF) persons receiving GAHT relative to the corresponding measures in cisgender reference groups, and to evaluate longitudinal changes in these laboratory measures following GAHT initiation. METHODS: The data for this longitudinal study included 624 TF and 438 transmasculine (TM) people as well as 4,090 cisgender males and 4,797 cisgender females enrolled in 3 integrated health systems. Time under observation was divided into 2 intervals: from the first blood test to the date of the first filled GAHT prescription and from GAHT initiation to the most recent ALT or AST measurement. Linear mixed models were used to compare changes in log-transformed ALT and AST values among transgender cohort members before and after GAHT initiation, and relative to the reference groups. The results were expressed as relative differences (in %) and the ratios of these differences (ratios-of-ratios) along with the 95% confidence intervals (CIs). OUTCOMES: Changes in ALT and AST levels among transgender people over time and relative to the corresponding changes in cisgender referents. RESULTS: Among TM study participants, the post GAHT ratios-of-ratios for AST were 1.61 (95% CI: 1.13, 2.31) and 1.57 (95% CI: 1.06, 2.31) relative to cisgender males and females respectively. For ALT, the corresponding comparisons yielded the ratios-of-ratios (95% CIs) of 2.06 (1.67, 2.54) and 1.90 (1.50, 2.40). No statistically significant changes were observed among TF participants. Other factors associated with higher liver enzyme levels included alcohol use/abuse and obesity. CLINICAL IMPLICATIONS: TM persons may experience modest increases in ALT and AST concentrations following testosterone initiation; however, clinical significance of the observed association remains unclear and requires further investigation. By contrast, feminizing GAHT is unlikely to induce appreciable changes in liver enzyme levels. STRENGTH AND LIMITATIONS: The strengths of this study are the longitudinal design and the ability to assemble an unselected cohort nested within large health systems. The main limitations include the lack of information on hormone levels and the inability to take into account GAHT doses and routes of administration. CONCLUSION: The influence of long-term GAHT on ALT and AST levels appears modest and not likely to reflect clinically meaningful changes in liver function. Hashemi L, Zhang Q, Getahun D, et al. Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy. J Sex Med 2021;18:1662-1675.

Conceptual approach to developing quality measures for transgender patients.

BACKGROUND: Valid and reliable quality measures can help catalyze improvements in health care. The care of transgender patients is ripe for quality measurement, as there is increasing awareness of the increasing prevalence of this population and the urgency of improving the health care they receive. While best practices may not exist for some aspects of transgender health care, other aspects are characterized by well-developed and highly evidence-based recommendations. Our objective was to create a list of potential quality measures for transgender care. METHODS AND RESULTS: In consultation with our advisory panel, which consisted of clinical and academic experts in transgender medicine, we selected eight prominent clinical practice guidelines of transgender health care for review. Our four team investigators carefully reviewed all eight clinical practice guidelines. Through the course of multiple consensus-building meetings, we iteratively refined items until we had agreed upon a list of forty potential quality measures, all of which met the criteria for quality measures set forth in the Center for Medicare and Medicaid Services Blueprint for developing quality measures. CONCLUSIONS: This manuscript explains the origin of the quality measures we developed, and also provides a useful roadmap to any group hoping to develop quality measures for a field that has not previously had any.

Beyond Gender Identity Disorder Diagnoses Codes: An Examination of Additional Methods to Identify Transgender Individuals in Administrative Databases.

BACKGROUND: Large administrative databases often do not capture gender identity data, limiting researchers' ability to identify transgender people and complicating the study of this population. OBJECTIVE: The objective of this study was to develop methods for identifying transgender people in a large, national dataset for insured adults. RESEARCH DESIGN: This was a retrospective analysis of administrative claims data. After using gender identity disorder (GID) diagnoses codes, the current method for identifying transgender people in administrative data, we used the following 2 strategies to improve the accuracy of identifying transgender people that involved: (1) Endocrine Disorder Not Otherwise Specified (Endo NOS) codes and a transgender-related procedure code; or (2) Receipt of sex hormones not associated with the sex recorded in the patient's chart (sex-discordant hormone therapy) and an Endo NOS code or transgender-related procedure code. SUBJECTS: Seventy-four million adults 18 years and above enrolled at some point in commercial or Medicare Advantage plans from 2006 through 2017. RESULTS: We identified 27,227 unique transgender people overall; 18,785 (69%) were identified using GID codes alone. Using Endo NOS with a transgender-related procedure code, and sex-discordant hormone therapy with either Endo NOS or transgender-related procedure code, we added 4391 (16%) and 4051 (15%) transgender people, respectively. Of the 27,227 transgender people in our cohort, 8694 (32%) were transmasculine, 3959 (15%) were transfeminine, and 14,574 (54%) could not be classified. CONCLUSION: In the absence of gender identity data, additional data elements beyond GID codes improves the identification of transgender people in large, administrative claims databases.

Understanding the Context of High- and Low-Testosterone Prescribing Facilities in the Veterans Health Administration (VHA): a Qualitative Study.

BACKGROUND: Inappropriate testosterone use and variations in testosterone prescribing patterns exist in the Veterans Health Administration (VHA) despite the presence of clinical guidelines. OBJECTIVE: We examined system and clinician factors that contribute to patterns of potentially inappropriate testosterone prescribing in VHA. DESIGN: Qualitative study using a positive deviance approach to understand practice variation in high- and low-testosterone prescribing sites. PARTICIPANTS: Twenty-two interview participants included primary care and specialty clinicians, key opinion leaders, and pharmacists at 3 high- and 3 low-testosterone prescribing sites. APPROACH: Semi-structured phone interviews were conducted, transcribed, and coded using a priori theoretical constructs and emergent themes. Case studies were developed for each site and a cross-case matrix was created to evaluate variation across high- and low-prescribing sites. KEY RESULTS: We identified four system-level domains related to variation in testosterone prescribing: organizational structures and processes specific to testosterone prescribing, availability of local guidance on testosterone prescribing, well-defined dissemination process for local testosterone polices, and engagement in best practices related to testosterone prescribing. Two clinician-level domains were also identified, specifically, structured initial testosterone prescribing process and specified follow-up testosterone prescribing process. High- and low-testosterone prescribing sites systematically varied in the four system-level domains, while the clinician-level domains looked similar across all sites. The third high-prescribing site was unusual in that it exhibited the four domains similar to the 3 low-prescribing sites at the time of our visit. This site had greatly reduced its prescribing of testosterone in the interim. CONCLUSIONS: Findings suggest that local organizational factors play an important role in influencing prescribing. Sites have the potential to transform their utilization patterns by providing access to specialty care expertise, an electronic health record-based system to facilitate guideline-concordant prescribing, well-defined dissemination processes for information, guidance from multiple sources, and clarity regarding best practices for prescribing.

Use of testosterone in men infected with human immunodeficiency virus in the veterans healthcare system.

Testosterone supplementation has been widely used in those infected with human immunodeficiency virus (HIV) for hypogonadism, and wasting. But with effective antiretroviral therapy and increasing recognition of atherosclerotic disease and adults infected with HIV, the risks of inappropriate testosterone use in HIV-infected patients are far better recognized than previously. Testosterone use has expanded among U.S. males, but few studies have examined prescribing in those infected with HIV. In a national cohort of males with at least one outpatient prescription in the Veterans Health Administration (VHA), we examined 9475 HIV-infected males, including 2484 who had received testosterone and a randomly selected 6991 who had not. For comparison, we identified 1,387,241 uninfected males (189,369 had received testosterone and a randomly selected 1,197,872 had not). We determined rates of new and prevalent testosterone use, and also examined the adequacy of the diagnostic evaluation that had preceded testosterone initiation among our HIV-infected and uninfected testosterone groups. Our main results were as follows. HIV-infected men had higher rates of initiation (0.8% vs. 0.4% in FY09; p < 0.001) and prevalence of testosterone use (2.2% vs. 0.8% in FY08; p < 0.001) compared to the uninfected men across the entire period. Trends of prescribing for both groups followed a similar pattern, rising from FY08, reaching a peak in FY13, and then dipping in FY 14. Only 1.1% of HIV-infected patients had a fully guideline-concordant workup before starting testosterone therapy, compared to 3.5% of uninfected patients (p < 0.001). In conclusion, testosterone use among HIV-infected patients in the VHA system rose to a peak in FY13 and has decreased somewhat since. Only a small minority of HIV-infected patients who receive testosterone therapy from VHA have undergone an appropriate workup before starting therapy, suggesting an opportunity for improvement.

Who Gets Testosterone? Patient Characteristics Associated with Testosterone Prescribing in the Veteran Affairs System: a Cross-Sectional Study.

BACKGROUND: There has been concern about the growing off-label use of testosterone. Understanding the context within which testosterone is prescribed may contribute to interventions to improve prescribing. OBJECTIVE: To evaluate patient characteristics associated with receipt of testosterone. DESIGN: Cross-sectional. SETTING: A national cohort of male patients, who had received at least one outpatient prescription within the Veterans Affairs (VA) system during Fiscal Year 2008- Fiscal Year 2012. PARTICIPANTS: The study sample consisted of 682,915 non-HIV male patients, of whom 132,764 had received testosterone and a random 10% sample, 550,151, had not. MAIN MEASURES: Conditions and medications associated with testosterone prescription. KEY RESULTS: Only 6.3% of men who received testosterone from the VA during the study period had a disorder of the testis, pituitary or hypothalamus associated with male hypogonadism. Among patients without a diagnosed disorder of hypogonadism, the use of opioids and obesity were the strongest predictors of testosterone prescription. Patients receiving >100 mg/equivalents of oral morphine daily (adjusted odds ratio = 5.75, p < 0.001) and those with body mass index (BMI) >40 kg/m2 (adjusted odds ratio = 3.01, p < 0.001) were more likely to receive testosterone than non-opioid users and men with BMI <25 kg/m2. Certain demographics (age 40-54, White race), comorbid conditions (sleep apnea, depression, and diabetes), and medications (antidepressants, systemic corticosteroids) also predicted a higher likelihood of testosterone receipt, all with an adjusted odds ratio less than 2 (p < 0.001). CONCLUSIONS: In the VA, 93.7% of men receiving testosterone did not have a diagnosed condition of the testes, pituitary, or hypothalamus. The strongest predictors of testosterone receipt (e.g., obesity, receipt of opioids), which though are associated with unapproved, off-label use, may be valid reasons for therapy. Interventions should aim to increase the proportion of testosterone recipients who have a valid indication.

Ascertainment of Testosterone Prescribing Practices in the VA.

BACKGROUND: Prescribing of exogenous testosterone is increasing. Because of the risks associated with testosterone, it is important to follow evidence-based procedures when initiating therapy. OBJECTIVE: We evaluated whether dispensing of testosterone was preceded by appropriate ascertainment of androgen deficiency, and consideration of potential contraindications, in accordance with practice guidelines. RESEARCH DESIGN: A cross-sectional study. SETTING: All outpatient clinics within Veterans Affairs (VA) during fiscal years 2009-2012 (FY09-FY12). SUBJECTS: A total of 111,631 men who had not previously received testosterone from VA, and received at least 1 testosterone dispensing during the study period. A 1-year "look-back" period was used to check for diagnostic tests that occurred before the first fill. MEASURES: Proportion who underwent appropriate diagnostic evaluation of androgen deficiency and ascertainment of contraindications for testosterone therapy during the year before receiving their first testosterone dispensing. RESULTS: New testosterone dispensing in VA increased from 20,437 in FY09 to 36,394 in FY12. Only 3.1% of men who received testosterone had 2 or more low (total or free) testosterone levels in the morning, LH and/or FSH level measured, and no contraindications to testosterone therapy. A total of 16.5% did not have their testosterone level checked at all. Among those prescribed therapy, 1.4% had prostate cancer, 7.6% had obstructive sleep apnea, and 3.5% had elevated hematocrit at baseline. CONCLUSIONS: Only a small proportion of men receiving testosterone in VA underwent appropriate testing, and some received this therapy despite important contraindications. Promoting a more uniform application of clinical guidelines may facilitate appropriate use of testosterone.

Outcomes of anticoagulation therapy in patients with mental health conditions.

BACKGROUND: Patients with mental health conditions (MHCs) experience poor anticoagulation control when using warfarin, but we have limited knowledge of the association between specific mental illness and warfarin treatment outcomes. OBJECTIVE: To examine the relationship between the severity of MHCs and outcomes of anticoagulation therapy. DESIGN: Retrospective cohort analysis. PARTICIPANTS: We studied 103,897 patients on warfarin for 6 or more months cared for by the Veterans Health Administration during fiscal years 2007-2008. We identified 28,216 patients with MHCs using ICD-9 codes: anxiety disorders, bipolar disorder, depression, post-traumatic stress disorder, schizophrenia, and other psychotic disorders. MAIN MEASURES: Outcomes included anticoagulation control, as measured by percent time in the therapeutic range (TTR), as well as major hemorrhage. Predictors included different categories of MHC, Global Assessment of Functioning (GAF) scores, and psychiatric hospitalizations. KEY RESULTS: Patients with bipolar disorder, depression, and other psychotic disorders experienced TTR decreases of 2.63 %, 2.26 %, and 2.92 %, respectively (p < 0.001), after controlling for covariates. Patients with psychotic disorders other than schizophrenia experienced increased hemorrhage after controlling for covariates [hazard ratio (HR) 1.24, p = 0.03]. Having any MHC was associated with a slightly increased hazard for hemorrhage (HR 1.19, p < 0.001) after controlling for covariates. CONCLUSION: Patients with specific MHCs (bipolar disorder, depression, and other psychotic disorders) experienced slightly worse anticoagulation control. Patients with any MHC had a slightly increased hazard for major hemorrhage, but the magnitude of this difference is unlikely to be clinically significant. Overall, our results suggest that appropriately selected patients with MHCs can safely receive therapy with warfarin.

Gender-Affirming Hormone Treatment and Metabolic Syndrome Among Transgender Veterans.

Importance: Gender-affirming hormone treatment (GAHT) is a common therapy for transgender individuals to reduce gender dysphoria and improve quality of life. Clarifying the long-term effects of GAHT remains a priority in transgender health research. Objective: To explore whether sex hormones (estradiol and testosterone) are associated with the development of metabolic syndrome in transgender veterans compared with cisgender veterans. Design, Setting, and Participants: This retrospective, longitudinal cohort study used International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes for gender dysphoria from the Veterans Health Administration national database to identify transfeminine and transmasculine veterans receiving documented feminizing (estradiol) or masculinizing (testosterone) treatment from January 1, 2006, to December 31, 2019, and for whom the GAHT initiation date and metabolic syndrome component-related data were available. Transgender veterans were matched to cisgender referents. Exposure: Gender-affirming hormone treatment. Main Outcomes and Measures: Metabolic syndrome z-scores were calculated based on body mass index, systolic blood pressure, and levels of high-density lipoprotein cholesterol, triglycerides, and blood glucose. Changes in mean z-scores were compared among the transgender and cisgender groups before and after the index date (corresponding to GAHT initiation) using a repeated-measures analysis of variance model. Results: The cohort included 1290 participants: 645 transgender (494 [38.3%] transfeminine, 151 [11.7%] transmasculine) and 645 cisgender (280 [21.7%] female, 365 [28.3%] male). Mean (SD) age at the index date was 41.3 (13.2) years. Metabolic syndrome z-scores changed significantly over time and differed significantly across groups. Overall, transmasculine veterans had the greatest percentage increase in mean (SEM) z-scores after vs before the index date (298.0% [57.0%]; P < .001), followed by cisgender females (108.3% [27.5%]; P < .001), cisgender males (49.3% [27.5%]; P = .02), and transfeminine persons (3.0% [10.7%]; P = .77). Conclusions and Relevance: In this cohort study, in both cisgender and transgender veterans, estradiol was associated with reduced metabolic syndrome risk, whereas testosterone was associated with increased risk. However, transmasculine individuals had the greatest risk and transfeminine individuals had the lowest risk of metabolic syndrome associated with these hormones. This is relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals and to potentially predict the risk of atherosclerotic cardiovascular disease, type 2 diabetes, systolic hypertension, insulin resistance, and nonalcoholic fatty liver disease.

Clinicians in the Veterans Health Administration initiate gender-affirming hormone therapy in concordance with clinical guideline recommendations.

Background: Gender-affirming hormone therapy (GAHT) is a common medical intervention sought by transgender and gender diverse (TGD) individuals. Initiating GAHT in accordance with clinical guideline recommendations ensures delivery of high-quality care. However, no prior studies have examined how current GAHT initiation compares to recommended GAHT initiation. Objective: This study assessed guideline concordance around feminizing and masculinizing GAHT initiation in the Veterans Health Administration (VHA). Methods: The sample included 4,676 veterans with a gender identity disorder diagnosis who initiated feminizing (n=3,547) and masculinizing (n=1,129) GAHT between 2007 and 2018 in VHA. Demographics and health conditions on veterans receiving feminizing and masculinizing GAHT were assessed. Proportion of guideline concordant veterans on six VHA guidelines on feminizing and masculinizing GAHT initiation were determined. Results: Compared to veterans receiving masculinizing GAHT, a higher proportion of veterans receiving feminizing GAHT were older (≥60 years: 23.7% vs. 6.3%), White non-Hispanic (83.5% vs. 57.6%), and had a higher number of comorbidities (≥7: 14.0% vs. 10.6%). A higher proportion of veterans receiving masculinizing GAHT were Black non-Hispanic (21.5% vs. 3.5%), had posttraumatic stress disorder (43.0% vs. 33.9%) and positive military sexual trauma (33.5% vs.16.8%; all p-values<0.001) than veterans receiving feminizing GAHT. Among veterans who started feminizing GAHT with estrogen, 97.0% were guideline concordant due to no documentation of contraindication, including venous thromboembolism, breast cancer, stroke, or myocardial infarction. Among veterans who started spironolactone as part of feminizing GAHT, 98.1% were guideline concordant as they had no documentation of contraindication, including hyperkalemia or acute renal failure. Among veterans starting masculinizing GAHT, 90.1% were guideline concordant due to no documentation of contraindications, such as breast or prostate cancer. Hematocrit had been measured in 91.8% of veterans before initiating masculinizing GAHT, with 96.5% not having an elevated hematocrit (>50%) prior to starting masculinizing GAHT. Among veterans initiating feminizing and masculinizing GAHT, 91.2% had documentation of a gender identity disorder diagnosis prior to GAHT initiation. Conclusion: We observed high concordance between current GAHT initiation practices in VHA and guidelines, particularly for feminizing GAHT. Findings suggest that VHA clinicians are initiating feminizing GAHT in concordance with clinical guidelines. Future work should assess guideline concordance on monitoring and management of GAHT in VHA.

Prevalence of Mild Cognitive Impairment and Alzheimer's Disease Identified in Veterans in the United States.

Background: Diagnostic codes can be instrumental for case identification in Alzheimer's disease (AD) research; however, this method has known limitations and cannot distinguish between disease stages. Clinical notes may offer more detailed information including AD severity and can complement diagnostic codes for case identification. Objective: To estimate prevalence of mild cognitive impairment (MCI) and AD using diagnostics codes and clinical notes available in the electronic healthcare record (EHR). Methods: This was a retrospective study in the Veterans Affairs Healthcare System (VAHS). Health records from Veterans aged 65 years or older were reviewed during Fiscal Years (FY) 2010-2019. Overall, 274,736 and 469,569 Veterans were identified based on a rule-based algorithm as having at least one clinical note for MCI and AD, respectively; 201,211 and 149,779 Veterans had a diagnostic code for MCI and AD, respectively. During FY 2011-2018, likely MCI or AD diagnosis was defined by≥2 qualifiers (i.e., notes and/or codes)≥30 days apart. Veterans with only 1 qualifier were considered as suspected MCI/AD. Results: Over the 8-year study, 147,106 and 207,225 Veterans had likely MCI and AD, respectively. From 2011 to 2018, yearly MCI prevalence increased from 0.9% to 2.2%; yearly AD prevalence slightly decreased from 2.4% to 2.1%; mild AD changed from 22.9% to 26.8%, moderate AD changed from 26.5% to 29.1%, and severe AD changed from 24.6% to 30.7. Conclusions: The relative distribution of AD severities was stable over time. Accurate prevalence estimation is critical for healthcare resource allocation and facilitating patients receiving innovative medicines.

Patient Characteristics Associated with Receiving Gender-Affirming Hormone Therapy in the Veterans Health Administration.

Purpose: This study aimed to examine patient characteristics associated with receipt of gender-affirming hormone therapy in the Veterans Health Administration (VHA). Methods: This cross-sectional study included a national cohort of 9555 transgender and gender diverse (TGD) patients with TGD-related diagnosis codes who received care in the VHA from 2006 to 2018. Logistic regression models were used to determine the association of health conditions and documented social stressors with receipt of gender affirming hormone therapy. Results: Of the 9555 TGD patients, 57.4% received gender-affirming hormone therapy in the VHA. In fully adjusted models, patients who had following characteristics were less likely to obtain gender-affirming hormones in the VHA: Black, non-Hispanic versus white (adjusted odds ratio [aOR]: 0.61; 95% confidence interval [CI]: 0.52-0.72), living in the Northeast versus the West (aOR: 0.72; 95% CI: 0.62-0.84), a documented drug use disorder (aOR: 0.56; 95% CI: 0.47-0.68), ≥3 versus no comorbidities (aOR: 0.44; 95% CI: 0.34-0.57), and ≥3 versus no social stressors (aOR: 0.42; 95% CI: 0.30-0.58; all p<0.001). Younger patients aged 21-29 years were almost 3 times more likely to receive gender affirming hormone therapy in the VHA than those aged ≥60 (aOR: 2.98; 95% CI: 2.55-3.47; p<0.001). Conclusion: TGD individuals who were older, Black, non-Hispanic, and had more comorbidities and documented social stressors were less likely to receive gender-affirming hormone therapy in the VHA. Further understanding of patient preferences in addition to clinician- and site-level determinants that may impact access to gender-affirming hormone therapy for TGD individuals in the VHA is needed.