Assessing and Addressing the Risk of Venous Thromboembolism Across the Spectrum of Gender Affirming Care: A Review.

OBJECTIVE: Accumulating evidence demonstrates that gender affirming hormone therapy (GAHT) improves mental health outcomes in transgender persons. Data specific to the risks associated with GAHT for transgender persons continue to emerge, allowing for improvements in understanding, predicting, and mitigating adverse outcomes while informing discussion about desired effects. Of particular concern is the risk of venous thromboembolism (VTE) in the context of both longitudinal GAHT and the perioperative setting. Combining what is known about the risk of VTE in cisgender individuals on hormone therapy (HT) with the evidence for transgender persons receiving HT allows for an informed approach to assess underlying risk and improve care in the transgender community. OBSERVATIONS: Hormone formulation, dosing, route, and duration of therapy can impact thromboembolic risk, with transdermal estrogen formulations having the lowest risk. There are no existing risk scores for VTE that consider HT as a possible risk factor. Risk assessment for recurrent VTE and bleeding tendencies using current scores may be helpful when assessing individual risk. Gender affirming surgeries present unique perioperative concerns, and certain procedures include a high likelihood that patients will be on exogenous estrogens at the time of surgery, potentially increasing thromboembolic risk. CONCLUSIONS AND RELEVANCE: Withholding GAHT due to potential adverse events may cause negative impacts for individual patients. Providers should be knowledgeable about the management of HT in transgender individuals of all ages, as well as in the perioperative setting, to avoid periods in which transgender individuals are off GAHT. Treatment decisions for both anticoagulation and HT should be individualized and tailored to patients' overall goals and desired outcomes, given that the physical and mental health benefits of gender affirming care may outweigh the risk of VTE.

Development of a Smartphone App to Predict and Improve the Rates of Suicidal Ideation Among Transgender Persons (TransLife): Qualitative Study.

BACKGROUND: Transgender people are at a high risk of suicidal ideation, suicide attempts, and deaths. Among transgender individuals, 77% and 41% engage in suicidal ideation and suicide attempt in their lifetime, respectively, which exceeds the general population rates (9.2% and 2.7%, respectively). Traditionally, suicide risk factors have been studied over a long period between measurements, making it difficult to understand the short-term variability in suicide risk. Mobile phone apps offer an opportunity to understand the immediate precursors of suicidality through the assessment of behaviors and moods in real time. This is the first study to use a mobile phone app (TransLife) to understand the short-term risk factors for suicide among transgender individuals. OBJECTIVE: This study aims to beta test the usability of an evidence-informed mobile health (mHealth) suicide prevention phone app, TransLife. The primary aims are to obtain preliminary data on user engagement and satisfaction with the app, and to assess the feasibility of completing ecological momentary assessments (mood logs) within the app. METHODS: We used qualitative methods and an exploratory research approach that combined naturalistic app use, focus groups, and semistructured phone interviews. The focus group was informed about the development of the prototype. We conducted a 3-week evaluation to determine engagement and obtain detailed user feedback about the app. After participation in the pilot, phone-based, semistructured, and audio-recorded exit interviews were conducted with the research participants. RESULTS: In total, 16 transgender individuals participated in this study. On average, users logged in 4 (SD 2.7) times a week and spent approximately 5 (SD 3.5) minutes on the app per log-in. A total of 6 major themes emerged in this study. These themes focused on the app's functionality, satisfaction with using the app, perceived ease of use, perceived safety of providing personal data within the app, trusting the app enough to share personal feelings, and features that make this app engaging. These themes suggest that TransLife is an engaging, useful, and acceptable mHealth intervention. Participants reported that the app was easy to use and understand, supported mental self-care, promoted self-awareness, and helped them identify triggers of negative moods. CONCLUSIONS: The results of this pilot study indicate that TransLife is an engaging, acceptable, and potentially effective mHealth intervention. Transgender participants reported many advantages of using TransLife, such as being able to track their mood, connecting to the community, and accessing local resources. This study provides initial support for the acceptability and usability of TransLife as an mHealth intervention designed for the transgender community.

Venous Thrombotic Risk in Transgender Women Undergoing Estrogen Therapy: A Systematic Review and Metaanalysis.

BACKGROUND: Transgender women are female individuals who were recorded men at birth based on natal sex. Supporting a person's gender identity improves their psychological health, and gender-affirming hormones reduce gender dysphoria and benefit mental health. For transgender women, estrogen administration has clinically significant benefits. Previous reviews have reported conflicting literature on the thrombotic risk of estrogen therapy in transgender women and have highlighted the need for more high-quality research. CONTENT: To help address the gap in understanding thrombotic risk in transgender women receiving estrogen therapy, we performed a systematic literature review and metaanalysis. Two evaluators independently assessed quality using the Ottawa Scale for Cohort Studies. The Poisson normal model was used to estimate the study-specific incidence rates and the pooled incidence rate. Heterogeneity was measured using Higgins I 2 statistic. The overall estimate of the incidence rate was 2.3 per 1000 person-years (95% CI, 0.8-6.9). The heterogeneity was significant (I 2 = 74%; P = 0.0039). SUMMARY: Our study estimated the incidence rate of venous thromboembolism in transgender women prescribed estrogen to be 2.3 per 1000 person-years, but because of heterogeneity this estimate cannot be reliably applied to transgender women as a group. There are insufficient data in the literature to partition by subgroup for subgroup prohibiting the analysis to control for tobacco use, age, and obesity, which is a major limitation. Additional studies of current estrogen formulations, modes of administration, and combination therapies, as well as studies in the aging transgender population, are needed to confirm thrombotic risk and clarify optimal therapy regimens.

A REVIEW OF BREAST DEVELOPMENT IN CISGENDER WOMEN AND IMPLICATIONS FOR TRANSGENDER WOMEN.

Objective: The objective of this article is to describe the hormonal pathways required for breast development in cisgender women and to review the current available literature describing breast growth and breast cancer risk in transgender women. Methods: Literature review and discussion. Results: Early mammary tissue development occurs prenatally. This process is hormone-independent and occurs similarly in males and females. Breast tissue is quiescent until puberty, at which time surging estrogen levels in cisgender girls mediate breast development and growth. Adult breast tissue composition further evolves in cisgender women during pregnancy, lactation, and menopause, revealing the ever-changing interplay between breast structure and hormonal environment. Conclusion: Breast growth is a significant physical endpoint in the hormonal treatment of transgender women. Transgender hormone regimens, which typically pair an estrogen with an anti-androgen, can help achieve this goal.

The Perioperative Care of the Transgender Patient.

An estimated 25 million people identify as transgender worldwide, approximately 1 million of whom reside in the United States. The increasing visibility and acceptance of transgender people makes it likely that they will present in general surgical settings; therefore, perioperative health care providers must develop the knowledge and skills requisite for the safe management of transgender patients in the perioperative setting. Extant guidelines, such as those published by the World Professional Association for Transgender Health and the University of California San Francisco Center of Excellence for Transgender Health, serve as critical resources to those caring for transgender patients; however, they do not address their unique perioperative needs. It is essential that anesthesia providers develop the knowledge and skills necessary for safely managing transgender patients in the perioperative setting. This review provides an overview of relevant terminology, the imperative for the provision of culturally sensitive care, and guidelines for preoperative, intraoperative, and postoperative management of the transgender patient.

When Gender Identity Doesn't Equal Sex Recorded at Birth: The Role of the Laboratory in Providing Effective Healthcare to the Transgender Community.

BACKGROUND: Transgender is an umbrella term used to describe individuals who identify with a gender incongruent to or variant from their sex recorded at birth. Affirming gender identity through a variety of social, medical, and surgical interventions is critical to the mental health of transgender individuals. In recent years, awareness surrounding transgender identities has increased, which has highlighted the health disparities that parallel this demographic. These disparities are reflected in the experience of transgender patients and their providers when seeking clinical laboratory services. CONTENT: Little is known about the effect of gender-affirming hormone therapy and surgery on optimal laboratory test interpretation. Efforts to diminish health disparities encountered by transgender individuals and their providers can be accomplished by increasing social and clinical awareness regarding sex/gender incongruence and gaining insight into the physiological manifestations and laboratory interpretations of gender-affirming strategies. This review summarizes knowledge required to understand transgender healthcare including current clinical interventions for gender dysphoria. Particular attention is paid to the subsequent impact of these interventions on laboratory test utilization and interpretation. Common nomenclature and system barriers are also discussed. SUMMARY: Understanding gender incongruence, the clinical changes associated with gender transition, and systemic barriers that maintain a gender/sex binary are key to providing adequate healthcare to transgender community. Transgender appropriate reference interval studies are virtually absent within the medical literature and should be explored. The laboratory has an important role in improving the physiological understanding, electronic medical system recognition, and overall social awareness of the transgender community.

Gender-Affirming Care for Older Transgender and Gender Diverse Adults.

In the United States, it is estimated that 0.3% of Americans aged 65 and older, or almost 172,000 individuals, identify as transgender. Aging comes with a unique set of challenges and experiences for this population, including health care disparities, mental health concerns, and social isolation. It is crucial for clinicians to use a patient-centered and trauma-informed care approach to address their specific needs and provide evidence-based quality health care, including preventive screenings, mental health support, and advocating for legal protections.

An Exploratory Study to Describe Transgender People with HIV Who Accessed Medicaid and Their Viral Suppression Over Time in New York City, 2013-2017.

Purpose: Although HIV surveillance contains information on HIV outcomes among transgender persons with HIV (TPWH), it does not include other important data, for example, gender-affirming health care, which may influence viral suppression (VS). We describe TPWH accessing Medicaid and the association of gender-affirming surgery with VS. Methods: Through matching Medicaid claims with HIV registry data, a cohort of previously identified TPWH in Medicaid was compared to cisgender women and men in terms of VS in 2013-2017 in New York City. Medicaid claims were used to identify TPWH who obtained gender-affirming surgery (e.g., chest, genital surgeries). We described the VS of those who had surgery and examined temporal trends in VS pre- and postsurgery and by surgery type. Results: 1730 TPWH were enrolled in Medicaid and in HIV care in 2013-2017. Overall for VS at last laboratory, TPWH in Medicaid had lower VS (76.0%) than cisgender women (80.4%) and men (83.3%). The exception was the 185 TPWH who obtained gender-affirming surgery (86.5%). Among 160 TPWH in Medicaid who obtained gender-affirming surgery and achieved VS, VS increased presurgery (66.3% 2 years prior, 76.9% 1 year prior) and remained high 1 year after (86.3%) and 2 years after (87.7%) (the last percentage is only among those who had surgery before 2017, N=81). Conclusion: Gender-affirming surgery may be an important motivator to becoming virally suppressed and was associated with sustained high VS, which can lead to improved survival and quality of life. Medicaid and other insurers should consider improving access to gender-affirming surgery among TPWH.

Improving Data on the HIV Epidemic in New York City by Identifying Transgender Persons in Medicaid in 2013-2017.

Purpose: Undercounting of transgender people with HIV (PWH) in New York City (NYC) remains prevalent. We sought to improve our ability to accurately enumerate transgender PWH and address their needs for gender-affirming health care. Methods: We enhance previous algorithms used to identify transgender beneficiaries, using diagnoses, prescriptions, and sex at birth from Medicaid claims in 2013-2017. We then matched beneficiaries to individuals diagnosed with HIV in the HIV surveillance registry to identify transgender PWH. Results: Our algorithm identified 6043 transgender persons who accessed Medicaid in 2013-2017, with 1472 (24%) reported to the HIV registry, 1168 (79%) of whom were accurately identified as transgender in the registry. We found 292 transgender persons in the registry that had accessed Medicaid but were not identified by our algorithm, for a total of 6335 transgender persons accessing Medicaid (0.1% of the NYC Medicaid population), including 1764 transgender PWH (28% of transgender persons accessing Medicaid). From 2013 to 2017, there was a 35% increase in transgender persons identified in Medicaid claims using our algorithm. Conclusion: We identified a large number of transgender persons in Medicaid, many of whom were PWH. We saw a sizeable increase over the 5-year period, likely due, in part, to expansion of Medicaid policy to cover gender-affirming health care. Given the high proportion of transgender PWH accessing Medicaid, Medicaid claims data are a valuable source of health information for the transgender population, a group that is often difficult to identify due to issues of underreporting, stigma, reduced access to appropriate care, and misgendering by health care personnel.

Oral estrogen leads to falsely low concentrations of estradiol in a common immunoassay.

Objectives: Recently, an estradiol immunoassay manufacturer (Beckman Coulter, USA) issued an 'important product notice' alerting clinical laboratories that their assay (Access Sensitive Estradiol) was not indicated for patients undergoing exogenous estradiol treatment. The objective of this analysis was to evaluate immunoassay bias relative to liquid chromatography tandem mass spectrometry (LC-MS/MS) in transgender women and to examine the influence of unconjugated estrone on measurements. Design: Cross-sectional secondary analysis. Methods: Estradiol concentrations from 89 transgender women were determined by 3 immunoassays (Access Sensitive Estradiol ('New BC') and Access Estradiol assays ('Old BC'), Beckman Coulter; Estradiol III assay ('Roche'), Roche Diagnostics) and LC-MS/MS. Bias was evaluated with and without adjustment for estrone concentrations. The number of participants who shifted between three estradiol concentration ranges for each immunoassay vs LC-MS/MS (>300 pg/mL, 70-300 pg/mL, and <70 pg/mL) was calculated. Results: The New BC assay had the largest magnitude overall bias (median: -34%) and was -40%, -22%, and -10%, among participants receiving tablet, patch, or injection preparations, respectively. Overall bias was -12% and +17% for the Roche and Old BC assays, respectively. When measured with the New BC assay, 18 participants shifted to a lower estradiol concentration range (vs 9 and 10 participants based on Roche or Old BC assays, respectively). Adjustment for estrone did not minimize bias. Conclusions: Immunoassay measurement of estradiol in transgender women may lead to falsely decreased concentrations that have the potential to affect management. A multidisciplinary health care approach is needed to ensure if appropriate analytical methods are available.

Overview of Factors Associated with HIV Viral Load Suppression in Transgender Women.

BACKGROUND: Transgender women face a significantly higher HIV burden than their cisgender counterparts around the world with worse treatment outcomes in almost all categories. CONTENT: A mini-review of the available literature discussing HIV risk and factors associated with HIV viral load suppression in transgender women. SUMMARY: This review discusses the disparities transgender women face that contribute to both of these factors including race as well as social determinants of health and how they affect the HIV treatment cascade in this population.

Improved Rates of Cervical Cancer Screening Among Transmasculine Patients Through Self-Collected Swabs for High-Risk Human Papillomavirus DNA Testing.

Introduction: Nearly all cervical cancer cases are caused by one of several high-risk strains of the human papillomavirus (hr-HPV). Transmasculine (TM) individuals (persons who have a masculine spectrum gender identity, but were recorded female at birth) have low adherence to standard cervical cancer screening modalities. Introduction of self-collected vaginal swabs for hr-HPV DNA testing may promote initiation and adherence to cervical cancer screening among TM individuals to narrow screening disparities. The purpose of this study was to assess the rate of cervical cancer screening among TM individuals following the introduction of self-collected swabbing for hr-HPV DNA testing in comparison to clinician-administered cervical specimen collection. Methods: Rates of uptake and adherence to cervical cancer screening among TM individuals were assessed before and after the clinical introduction of self-collected swab testing in October 2017. Rates were compared with the rates of cervical cancer screening among cisgender women at a colocated Comprehensive Health Program during the time period of review. Results: Of the 121 TM patients seen for primary care in the 6-month baseline period before the October 2017 introduction of self-collected swabbing for hr-HPV DNA testing, 30 (25%) had cervical cancer screening documented in the electronic medical record. Following the implementation of self-swabbing, of 193 patients, 98 (51%) had a documented cervical cancer screening, a two-fold increase in the rates of adherence to cervical cancer screening (p<0.001). Conclusion: Self-collected swab testing for hr-HPV can increase rates of adherence to screening recommendations among an otherwise under-screened population.

The Mount Sinai Patient-Centered Preoperative Criteria Meant to Optimize Outcomes Are Less of a Barrier to Care Than WPATH SOC 7 Criteria Before Transgender-Specific Surgery.

Objectives: With expanding coverage of gender-affirming care in the United States, many insurers default to the World Professional Association for Transgender Health (WPATH) Standards of Care 7 (SOC 7) to establish eligibility requirements for surgery coverage. Informed by bariatric and transplant surgery evaluation models, the Mount Sinai Center for Transgender Medicine and Surgery (CTMS) developed patient-centered criteria to assess readiness for surgery, focusing on concerns that could impair recovery. To make recommendations for the next version of the WPATH SOC, SOC 8, we compared Mount Sinai patient-centered surgical readiness criteria with the WPATH SOC 7 criteria. Methods: Data were extracted from a deidentified data set developed as part the quality dashboard for CTMS. The data set included all patients seeking vaginoplasty who were evaluated by a single mental health provider, from July 2016 through August 2018, and who completed the full CTMS assessment. The number of patients eligible for surgery based on the Mount Sinai CTMS criteria was compared with the number of patients eligible for surgery according to WPATH SOC 7 criteria. Results: Of 139 patients identified, 63 (45%) were ready for surgery immediately based on the Mount Sinai patient-centered model. By contrast, only 21 (15%) out of the 139 met criteria for surgery based on WPATH SOC 7. Fifty patients (40%) were ready for surgery as per Mount Sinai patient-centered readiness review but not WPATH criteria. Conclusion: An assessment designed to better prepare patients for surgery may also result in fewer barriers to care than existing criteria used by insurance companies in the United States.

Managing the risk of venous thromboembolism in transgender adults undergoing hormone therapy.

Introduction: Venous thromboembolism (VTE) is a potential risk of estrogen therapy. However, data show an improvement in the quality of life for transgender people who use feminizing hormone therapy. With few transgender-specific data, guidance may be drawn from cisgender (nontransgender) data, with a focus on hormonal birth control and postmenopausal hormone replacement therapy (HRT). The aim of this review is to examine the degree to which routes of administration, patient comorbidities, and type of hormone utilized affect the safety of estrogen therapy. Methods: We identified 6,349 studies by searching PubMed with the terms "transgender", "estrogen", "VTE", and "HRT". Of these, there were only 13 studies between 1989 and 2018 that investigated the effects of hormone therapy, including types of estrogens used, in transgender women and men. Results: The data suggest that the route of hormone administration, patient demographics, and patient comorbidities all affect estrogen's link with VTE. For example, avoiding ethinyl estradiol might make the use of hormone therapy in trans feminine individuals safer than oral birth control. Data from both cis and trans groups suggest additional VTE risk associated with the use of progestins. While transdermal estrogens dosed up to 0.1 mg/day or below appear lower risk for VTE than other forms of estrogen, it is unclear whether this is related to the delivery method or a dose effect. Finally, even if the risk from exogenous estrogen use remains significant statistically, the absolute clinical risk remains low. Conclusion: Clinicians should avoid the use of ethinyl estradiol. Additionally, data suggest that progestins should be avoided for transgender individuals. Further study of the relationship between estrogen use and the risk of VTE will serve to inform the safest care strategies for transgender individuals.

Chlamydia trachomatis Infection of the Neovagina in Transgender Women.

We report 2 cases of neovaginal Chlamydia trachomatis infection in transgender women who underwent penile-inversion vaginoplasty procedures with integrated peritoneum and urethral grafts. These tissue types may have facilitated C. trachomatis infection. Medical providers should implement neovaginal screening for bacterial sexually transmitted infections in transgender patients at risk for infection.

Identifying Medicare Beneficiaries Accessing Transgender-Related Care in the Era of ICD-10.

Purpose: The study purpose was to describe trends in the size and demographics of the population of transgender Medicare beneficiaries identified using International Classification of Diseases (ICD) Clinical Modification codes over time. We also assessed how the change from ICD, Ninth Revision (ICD-9) diagnosis codes to ICD, 10th Revision (ICD-10) diagnosis codes in October 2015 has affected the ability to identify transgender beneficiaries within claims data. Methods: We used Medicare Fee-for-Service claims within the Centers for Medicare & Medicaid Services Chronic Conditions Data Warehouse from 2010 through 2016 to identify transgender beneficiaries. We linked these data to Medicare enrollment records to study demographic trends. Results: Within the Medicare program, the number of beneficiaries identified as transgender through claims data in each year has increased from 2088 beneficiaries in 2010 to 10,242 beneficiaries in 2016 (a 390% increase). The highest numbers of transgender beneficiaries were identified in 2015 and 2016, which coincide with the change to ICD-10. Similarly, more beneficiaries were identified as transgender in the 12 months after the change to ICD-10 (N = 8733) than in the 12 months before (N = 4857). Conclusion: Given that a first and critical step to better understand and eliminate health disparities and deliver culturally competent care is to identify and characterize the population of interest, this study provides an innovative view into how the change to the ICD-10 coding system affects the ability to study a transgender cohort within Medicare claims data.