Receipt of Gender-Affirming Surgeries Among Transgender and Gender Diverse Veterans.

BACKGROUND: Gender-affirming surgery (GAS) can be an important part of comprehensive care for transgender and gender diverse (TGD) individuals, but this care is not provided by the Department of Veterans Affairs (VA) because of an exclusion in the medical benefits package. OBJECTIVE: To describe the receipt of GAS by veterans and assess the associations between key sociodemographic characteristics and receipt of chest ("top") and genital ("bottom") surgeries. DESIGN: Cross-sectional national survey (the GendeR Affirming Care Evaluation (GRACE)), among TGD Veterans conducted between September 2022 and July 2023. PARTICIPANTS: A total of 6653 Veterans (54% response rate) completed the survey. MAIN MEASURES: Self-reported "top" and "bottom" GAS were key outcomes. Covariates included gender identity, sex assigned at birth, age, race, ethnicity, income, employment status, education, relationship status, sexual orientation, and geographic region. KEY RESULTS: Among all respondents, 39% had ≥ 1 GAS. Among the 4430 veterans interested in top surgery, 38% received it; 23% of 3911 veterans interested in bottom surgery had received it. In multivariable models, older age (50 + vs. 18-39) was associated with higher receipt of top and bottom surgery while nonbinary gender identity (vs. binary gender identity), lower household income (< $50,000 vs. > $75,000), less education (less than a college graduate vs. Master's degree or more), sexual orientations other than heterosexual, and residing in a region other than the Pacific were associated with lower receipt of top and bottom surgery. Individuals assigned male (vs. assigned female) at birth had lower receipt of top surgery and higher receipt of bottom surgery. CONCLUSIONS: GAS receipt was low and there were important disparities by gender, sex, income, education, sexual orientation, and region. By removing the exclusion to providing GAS, VA could reduce barriers to accessing GAS and decrease disparities among TGD veterans.

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.

Development and Validation of Quality Measures for Testosterone Prescribing.

Context: Accurate measures to assess appropriateness of testosterone prescribing are needed to improve prescribing practices. Objective: This work aimed to develop and validate quality measures around the initiation and monitoring of testosterone prescribing. Methods: This retrospective cohort study comprised a national cohort of male patients receiving care in the Veterans Health Administration who initiated testosterone during January or February 2020. Using laboratory data and diagnostic codes, we developed 9 initiation and 7 monitoring measures. These were based on the current Endocrine Society guidelines supplemented by expert opinion and prior work. We chose measures that could be operationalized using national VA electronic health record (EHR) data. We assessed criterion validity for these 16 measures by manual review of 142 charts. Main outcome measures included positive and negative predictive values (PPVs, NPVs), overall accuracy (OA), and Matthews Correlation Coefficients (MCCs). Results: We found high PPVs (>78%), NPVs (>98%), OA (≥94%), and MCCs (>0.85) for the 10 measures based on laboratory data (5 initiation and 5 monitoring). For the 6 measures relying on diagnostic codes, we similarly found high NPVs (100%) and OAs (≥98%). However, PPVs for measures of acute conditions occurring before testosterone initiation (ie, acute myocardial infarction or stroke) or new conditions occurring after initiation (ie, prostate or breast cancer) PPVs were much lower (0% to 50%) due to few or no cases. Conclusion: We developed several valid EHR-based quality measures for assessing testosterone-prescribing practices. Deployment of these measures in health care systems can facilitate identification of quality gaps in testosterone-prescribing and improve care of men with hypogonadism.

Social Stressors and Health Among Older Transgender and Gender Diverse Veterans.

Purpose: Health disparities in transgender and gender diverse (TGD) veterans compared with cisgender veterans have been documented. However, there is a paucity of literature focused on older TGD veterans. We assessed health conditions and social stressors in older TGD veterans compared with matched cisgender veterans. Methods: Using gender identity disorder diagnosis codes, we identified 1244 TGD veterans (65+ years of age) receiving care in the Veterans Health Administration (VHA) from 2006 to 2018. These TGD veterans were then matched to 3732 cisgender veterans based on age, VHA site, and date of care in VHA. Results: In adjusted models, TGD veterans compared with cisgender veterans were less likely to have alcohol use disorder (adjusted odds ratio [AOR; 95% confidence interval]: [0.70; 0.58-0.85]), drug use disorder (0.59; 0.47-0.74), tobacco use (0.75; 0.65-0.86), and anxiety (0.74; 0.62-0.90). However, compared with cisgender veterans, TGD veterans were more likely to experience depression (1.63; 1.39-1.93), Alzheimer's disease (8.95; 4.25-18.83), cancer (1.83; 1.56-2.14), violence (1.82; 1.14-2.91), social/familial problems (2.45; 1.99-3.02), lack of access to care/transportation (2.23; 1.48-3.37), and military sexual trauma (2.59; 1.93-3.46). Furthermore, compared with cisgender veterans, TGD veterans were more likely to have documentation of a higher count of social stressors: 1 or more stressors (1.64; 1.38-1.95) and 2 or more stressors (1.22; 1.01-1.49). Conclusion: Despite significant disparities in social stressors and health conditions compared with cisgender veterans, TGD veterans had a lower likelihood of substance use and anxiety. Interventions are needed to mitigate social stressors and improve health among the older TGD veteran population.

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.

Considering Quality Measures for the Care of Transgender Patients: Preliminary Findings from a Technical Expert Panel.

Purpose: Transgender (TG) individuals are a historically understudied and underserved patient population. Although clinical guidelines for the care of TG patients exist, quality measures (QMs) specific to this population are lacking. The goal of this study was to obtain expert input on aspects of care for which quality measurement may be appropriate and describe feedback on candidate QMs. Methods: We convened a virtual technical expert panel in September 2020 with six experts in TG medical care. Experts participated in a guided discussion and provided numeric ratings on dimensions of measure suitability (importance, validity/reliability, feasibility, and ease of understanding) for eight candidate QMs spanning multiple care domains (e.g., laboratory testing/monitoring, cancer screening, and sexually transmitted infection screening). Results: Panelists acknowledged high importance and potential to improve care for some candidate QMs, particularly those related to laboratory testing before initiating and during hormone therapy. Numeric ratings of QMs varied but tended to be higher for testing-focused QMs. Experts raised concerns about overly prescriptive language for some QMs and emphasized the importance of considering more flexible specifications to accommodate diverse care scenarios-including care provided to nonbinary individuals-and align with the individualized nature of gender-affirming care. Conclusion: These preliminary findings support a potential role for QMs in improving quality of care for TG patients. Measures related to laboratory testing/monitoring for patients who receive or plan to initiate hormone therapy may be feasible and promising to explore in the future. Additional larger-scale efforts are needed to develop and test QMs for the care of TG individuals.

Prevalence and Co-occurrence of Alcohol, Nicotine, and Other Substance Use Disorder Diagnoses Among US Transgender and Cisgender Adults.

Importance: Substance use disorders are a major source of morbidity and mortality in the United States. National data comparing the prevalence of substance use disorder diagnoses (SUDDs) among transgender and cisgender individuals are lacking in the United States. Objectives: To investigate the prevalence of SUDDs among transgender and cisgender adults and to identify within-group and between-group differences by age, gender, and geographic location. Design, Setting, and Participants: This cross-sectional study used the OptumLabs Data Warehouse to analyze deidentified claims from approximately 74 million adults aged 18 years or older enrolled in commercial or Medicare Advantage insurance plans in 2017. A total of 15 637 transgender adults were identified based on a previously developed algorithm using a combination of International Classification of Diseases, Tenth Revision (ICD-10) transgender-related diagnosis and procedure codes and sex-discordant hormone prescriptions. A cohort of 46 911 cisgender adults was matched to the transgender cohort in a 3:1 ratio based on age and geographic location. Main Outcomes and Measures: SUDDs, based on ICD-10 codes, were assessed overall and compared between transgender and cisgender cohorts and by geographic region (ie, Northeast, Midwest, South, and West); age groups (eg, 18-25, 26-30, 31-35 years), and gender (ie, transfeminine [TF; assigned male sex at birth, identify along feminine gender spectrum], transmasculine [TM; assigned female sex at birth, identify along masculine gender spectrum], male, and female). Results: In this study of 15 637 transgender adults (4955 [31.7%] TM) and 46 911 cisgender adults (23 247 [50.4%] men), most (8627 transgender adults [55.2%]; 51 762 cisgender adults [55.2%]) were aged between 18 and 40 years, and 6482 transgender adults (41.5%) and 19 446 cisgender adults (41.5%) lived in the South. Comparing transgender to cisgender groups, significant differences were found in the prevalence of a nicotine (2594 [16.6%] vs 2551 [5.4%]; P < .001), alcohol (401 [2.6%] vs 438 [0.9%]; P < .001), and drug (678 [4.3%] vs 549 [1.2%]; P < .001) SUDDs. Among transgender adults, cannabis was the most prevalent drug SUDD (321 [2.1%]), followed by opioid SUDD (205 [1.3%]) and cocaine SUDD (81 [0.5%]), whereas among cisgender adults, cannabis and opioid SUDDs were equally prevalent (cannabis, 186 [0.4%]; opioid, 207 [0.4%]), followed by cocaine SUDD (59 [0.1%]). Conclusions and Relevance: In this study, the prevalence of SUDDs was significantly elevated among transgender adults relative to their cisgender peers. These findings underscore the need for culturally tailored clinical interventions to treat substance use disorder in transgender populations.

Health Outcomes Among Long-term Opioid Users With Testosterone Prescription in the Veterans Health Administration.

Importance: Androgen deficiency is common among male opioid users, and opioid use has emerged as a common antecedent of testosterone treatment. The long-term health outcomes associated with testosterone therapy remain unknown, however. Objective: To compare health outcomes between long-term opioid users with testosterone deficiency who filled testosterone prescriptions and those with the same condition but who did not receive testosterone treatment. Design, Setting, and Participants: This cohort study focused on men in the care of the Veterans Health Administration (VHA) facilities throughout the United States from October 1, 2008, to September 30, 2014. It included male veterans who were long-term opioid users, had low testosterone levels (<300 ng/dL), and received either a testosterone prescription or any other prescription. It excluded male patients with HIV infection, gender dysphoria, or prostate cancer and those who received testosterone in fiscal year 2008. Data were analyzed from April 1, 2017, to April 30, 2019. Exposure: Prescription for testosterone. Main Outcomes and Measures: All-cause mortality and incidence of major adverse cardiovascular events (MACE), vertebral or femoral fractures, and anemia during the 6-year follow-up through September 30, 2015. Results: After exclusions, 21 272 long-term opioid users (mean [SD] age, 53 [10] years; n = 16 689 [78.5%] white) with low total or free testosterone levels were included for analysis, of whom 14 121 (66.4%) received testosterone and 7151 (33.6%) did not. At baseline, compared with opioid users who did not receive testosterone, long-term opioid users who received testosterone treatment were more likely to have obesity (43.7% vs 49.0%; P < .001), hyperlipidemia (43.0% vs 48.8%; P < .001), and hypertension (53.9% vs 55.2%; P = .07) but had lower prevalence of coronary artery disease (15.9% vs 12.9%; P < .001) and stroke (2.4% vs 1.3%; P < .001). After adjusting for covariates, opioid users who received testosterone had significantly lower all-cause mortality (hazard ratio [HR] = 0.51; 95% CI, 0.42-0.61) and lower incidence of MACE (HR = 0.58; 95% CI, 0.51-0.67), femoral or hip fractures (HR = 0.68; 95% CI, 0.48-0.96), and anemia (HR = 0.73; 95% CI, 0.68-0.79) during the follow-up period of up to 6 years, compared with their counterparts without a testosterone prescription. In covariate-adjusted models, men who received opioids plus testosterone were more likely to have resolved anemia compared with those who received opioids only during the 6-year follow-up (HR = 1.16; 95% CI, 1.02-1.31). Similar results were obtained in propensity score-matched models and when analyses were restricted to opioid users with noncancer pain or those who did not receive glucocorticoids. Conclusions and Relevance: This study found that, in the VHA system, male long-term opioid users with testosterone deficiency who were treated with opioid and testosterone medications had significantly lower all-cause mortality and significantly lower incidence of MACE, femoral or hip fractures, and anemia after a multiyear follow-up. These results warrant confirmation through a randomized clinical trial to ascertain the efficacy of testosterone in improving health outcomes for opioid users with androgen deficiency.

Gender differences in prescribing of zolpidem in the Veterans Health Administration.

OBJECTIVES: Use of nonbenzodiazepine sedative hypnotics, especially zolpidem, has grown substantially, raising concerns about safety. Here, we evaluated prescribing patterns of zolpidem in the Veterans Health Administration. STUDY DESIGN: A cross-sectional study of veterans receiving zolpidem in the outpatient setting from October 1, 2011, to September 30, 2016. METHODS: The study population consisted of 500,332 zolpidem users (58,598 women and 441,734 men) and a random 10% sample (n = 631,449) of nonusers. We examined 2 outcomes related to inappropriate prescribing: high-dose zolpidem prescribing and overlap with benzodiazepines. We generated interrupted time series and logistic regression models to analyze these outcomes in men and women separately. RESULTS: In 2016, 29.7% of female veterans received an inappropriately high guideline-discordant dosage compared with 0.1% of male veterans (P <.001 for all reported comparisons). Furthermore, more women than men had overlapping benzodiazepine and zolpidem prescriptions (18.8% vs 14.3%). In fully adjusted models, inappropriately high doses were more commonly received by younger women (adjusted odds ratios [AORs]: 2.75 for 21-39 years and 2.97 for 40-49 years compared with ≥80 years) and women with substance use disorder (AOR, 1.48). In the second inappropriateness outcome models, women with anxiety (AOR, 2.28) or schizophrenia (AOR, 2.05) and men with cancer (AOR, 1.42), anxiety (AOR, 2.66), or schizophrenia (AOR, 2.46) were more likely to receive an overlapping prescription of zolpidem and benzodiazepines. CONCLUSIONS: We found evidence of inappropriate zolpidem prescribing among veterans, particularly women. Greater understanding of the drivers of this inappropriate prescribing is necessary to develop interventions to promote safer, more guideline-concordant prescribing.

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.

Diet quality, physical activity, smoking status, and weight fluctuation are associated with weight change in women and men.

The effect of diet quality on weight change, relative to other body weight determinants, is insufficiently understood. Furthermore, research on long-term weight change in U.S. adults is limited. We evaluated prospectively patterns and predictors of weight change in Framingham Offspring/Spouse (FOS) women and men (n = 1515) aged > or =30 y with BMI > or = 18.5 kg/m2 and without cardiovascular disease, diabetes, and cancer at baseline over a 16-y period. Diet quality was assessed using the validated Framingham Nutritional Risk Score. In women, older age (P < 0.0001) and physical activity (P < 0.05) were associated with lower weight gain. Diet quality interacted with former smoking status (P-interaction = 0.02); former smokers with lower diet quality gained an additional 5.2 kg compared with those with higher diet quality (multivariable-adjusted P-trend = 0.06). Among men, older age (P < 0.0001) and current smoking (P < 0.01) were associated with lower weight gain, and weight fluctuation (P < 0.01) and former smoking status (P < 0.0001) were associated with greater weight gain. Age was the strongest predictor of weight change in both women (partial R(2) = 11%) and men (partial R(2) = 8.6%). Normal- and overweight women gained more than obese women (P < 0.05) and younger adults gained more weight than older adults (P < 0.0001). Patterns and predictors of weight change differ by sex. Age in both sexes and physical activity among women as well as weight fluctuation and smoking status in men were stronger predictors of weight change than diet quality among FOS adults. Women who stopped smoking over follow-up and had poor diet quality gained the most weight. Preventive interventions need to be sex-specific and consider lifestyle factors.