The association of gender-affirming hormone therapy duration and body mass index on bone mineral density in gender diverse adults.

Introduction: Feminizing and masculinizing gender-affirming hormone therapy (fGAHT, mGAHT) results in bone mineral density (BMD) maintenance or improvement over time in transgender and gender diverse (TGD) adults. Mostly European TGD studies have explored GAHT's impact on BMD, but the association of BMI and BMD in TGD adults deserves further study. Objective: To determine whether GAHT duration or BMI are associated with BMD and Z-scores among TGD young adults. Methods: Cross-sectional study of nonsmoking TGD adults aged 18-40 years without prior gonadectomy or gonadotropin-releasing hormone agonist (GnRHa) therapy taking GAHT for > 1 year. BMD and Z-scores were collected from dual-energy x-ray absorptiometry. Associations between femoral neck, total hip, and lumbar spine BMDs and Z-scores and the predictors, GAHT duration and BMI, were estimated using linear regression. Results: Among 15 fGAHT and 15 mGAHT, mean BMIs were 27.6 +/- standard deviation (SD) 6.4 kg/m2 and 25.3 +/- 5.9 kg/m2, respectively. Both groups had mean BMDs and Z-scores within expected male and female reference ranges at all three sites. Higher BMI among mGAHT was associated with higher femoral neck and total hip BMDs (femoral neck: ß = 0.019 +/- standard error [SE] 0.007 g/cm2, total hip: ß = 0.017 +/- 0.006 g/cm2; both p < 0.05) and Z-scores using male and female references. GAHT duration was not associated with BMDs or Z-scores for either group. Conclusions: Z-scores in young, nonsmoking TGD adults taking GAHT for > 1 year, without prior gonadectomy or GnRHa, and with mean BMIs in the overweight range, were reassuringly within the expected ranges for age based on male and female references. Higher BMI, but not longer GAHT duration, was associated with higher femoral neck and total hip BMDs and Z-scores among mGAHT. Larger, prospective studies are needed to understand how body composition changes, normal or low BMIs, and gonadectomy affect bone density in TGD adults.

The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels.

Feminizing gender-affirming hormone therapy (GAHT) is the mainstay of treatment for many transgender and gender diverse (TGD) people. Injectable estradiol preparations are recommended by the World Professional Association for Transgender Health Standards of Care 8 and the Endocrine Society guidelines. Many patients prefer this route of administration, but few studies have rigorously assessed optimal dosing or route. We performed a scoping review of the available data on estradiol levels achieved with various dosages of estradiol injections in TGD adults on feminizing GAHT. We also report on testosterone suppression, route (i.e., subcutaneous vs. intramuscular), and type of injectable estradiol ester as well as timing of blood draw relative to the most recent dose, where available. The data we reviewed suggests that the current guidelines, which recommend starting doses 2-10 mg weekly or 5-30 mg every two weeks of estradiol cypionate or valerate, are too high and likely lead to patients having supraphysiologic levels across much of their injection cycle. The optimal starting dose for injectable estradiol remains unclear and whether it should differ for cypionate and valerate. Based on the data available, we suggest that clinicians start injectable estradiol valerate via subcutaneous or intramuscular injections at a dose ≤ 5 mg weekly and then titrate accordingly to keep levels within guideline recommended range. Future studies should assess timing of injections and subsequent levels more precisely across the injection cycle and between esters.

Approach to the Patient Navigating Body Mass Index Requirements for Gender-Affirming Surgery.

Body mass index (BMI) requirements for gender-affirming surgeries (GAS) present an obstacle to gender transition for many transgender and gender diverse (TGD) people. Furthermore, TGD people have unique barriers and preferences in managing their weight that must be considered. TGD patients frequently present to their endocrinologists for individualized, gender-affirming support to meet BMI cutoffs for GAS. This Approach to the Patient article combines expertise from several disciplines, including gender-affirming hormone management, weight management, mental health, gynecology, and plastic surgery. Multidisciplinary management considerations are offered for clinicians to assist TGD patients with obesity navigate BMI requirements to access GAS.

Considerations for Gender-Affirming Hormonal and Surgical Care Among Transgender and Gender Diverse Adolescents and Adults With Congenital Heart Disease.

BACKGROUND: Transgender and gender diverse (TGD) individuals and long-term survivors with adult congenital heart disease (ACHD) are both growing populations with specialized needs. No studies assess temporal trends or evaluate the care of TGD individuals with ACHD. METHODS AND RESULTS: Meetings between congenital cardiology and gender-affirming care specialists identified unique considerations in TGD individuals with ACHD. A retrospective chart review was then performed to describe patient factors and outpatient trends in those with an ACHD diagnosis undergoing gender-affirming hormonal or surgical care (GAHT/S) at 1 adult and 1 pediatric tertiary care center. Thirty-three TGD individuals with ACHD were identified, 21 with a history of GAHT/S. Fourteen (66%) had moderate or complex ACHD, 8 (38%) identified as transgender male, 9 (43%) transgender female, and 4 (19%) other gender identities. Three had undergone gender-affirming surgery. There were zero occurrences of the composite end point of unplanned hospitalization or thrombotic event over 71.1 person-years of gender-affirming care. Median age at first gender-affirming appointment was 16.8 years [interquartile range 14.8-21.5]. The most common treatment modification was changing estradiol administration from oral to transdermal to reduce thrombotic risk (n=3). An increasing trend was observed from zero TGD patients with ACHD attending a gender diversity appointment in 2012 to 14 patients in 2022. CONCLUSIONS: There is a growing population of TGD patients with ACHD and unique medical and psychosocial needs. Future studies must fully evaluate the reassuring safety profile observed in this small cohort. We share 10 actionable care considerations for providers with a goal of overseeing a safe and fulfilling gender transition across all TGD patients with ACHD.

ECHO "Bootcamp": An Innovative Training Model to Onboard Providers in the Care of Gender Diverse Patients.

Purpose: Extension for Community Health Outcomes (ECHO) is a model of continuing medical education meant to connect academic medical center-based specialists with community providers to increase capacity in managing complex health conditions. The purpose of this study was to evaluate the effectiveness of a shortened "bootcamp" ECHO model in increasing participant competence with topics related to transgender and gender diverse (TGD) health care and the impact of "bootcamp" participation on enrollment in an ongoing ECHO series. Methods: An ongoing monthly ECHO series was instituted on topics of TGD health. After 2 years, the team implemented a four-session "bootcamp" for four consecutive weeks during March 2022 to introduce foundational topics for new participants who had joined or were considering joining the ongoing series. Qualitative and quantitative results were collected from self-reported pre-/post-surveys as well as from in-session quizzes. Results: There were 71 participants in the "bootcamp" including health care providers and support staff. Attendees reported a 10.3% increase (p = 0.02) in self-reported comfort providing care to transgender patients. Pre-/post-knowledge improved in areas of health inequities (50% vs. 74% correct pre/post), surgical requirements (33% vs. 74%), and effects of masculinizing (55% vs. 70%) and feminizing (64% vs. 89%) hormone therapy. Prescribing providers reported a significant change across four areas of practice competency. Among 71 "bootcamp" participants, 15 registered for the ongoing program. Conclusion: Use of a "bootcamp" highlights ways to increase participant comfort and knowledge in providing TGD health care in a shortened timeframe and recruit new participants to an ongoing ECHO curriculum.

Approach to the Patient: Hormonal Therapy in Transgender Adults With Complex Medical Histories.

While endocrinologists continue to initiate gender-affirming hormone therapy (GAHT) in healthy transgender and gender diverse (TGD) patients, they may also encounter more TGD patients in their clinics with complex medical histories that influence the patient-provider shared decision-making process for initiating or continuing GAHT. The purpose of this Approach to the Patient article is to describe management considerations in 2 adults with thromboembolic disease and 2 adults with low bone mineral density in the setting of feminizing and masculinizing GAHT.

Filling a gap in care: addressing obesity in transgender and gender diverse patients.

Transgender and gender diverse (TGD) adults are more likely to have obesity compared to cisgender peers. Based on surveys, the TGD population experiences disparities in healthy lifestyle behaviors (e.g., physical activity, screen time) compared to reference groups. They also face significant socioeconomic and healthcare barriers to accessing affirming care and gender minority stress, potentially contributing to increased weight. Gender-affirming hormone therapy is associated with changes in body composition and increased weight, which may impact cardiometabolic risk trajectory. Obesity can also be a barrier to gender-affirming surgeries, and affirming weight management services tailored to TGD patients are an important gap in healthcare to address. This Perspective briefly reviews current literature on the unique barriers experienced by TGD people and their identified needs regarding weight management interventions. It also suggests areas for future research to best fill this gap in healthcare and research while supporting the provision of lifesaving gender-affirming care.

Meeting the Body Mass Index Requirement for Gender-affirming Surgery Using Antiobesity Medication.

One-fourth of transgender and gender diverse (TGD) patients presenting for initial gender-affirming surgery (GAS) consult is denied surgery due to obesity. Many surgery centers enforce body mass index (BMI) requirements for GAS because of concerns about perioperative risks, cosmetic outcomes, and reoperation. TGD people experience gender minority stress and disparities in lifestyle factors that likely contribute to excess weight gain. Gender-affirming hormone therapy has also been associated with increased body weight. Effective and affirming weight management interventions for TGD patients with overweight and obesity are currently lacking. We report the case of a 40-year-old transgender woman with a BMI of 39.6 kg/m2 who presented for weight loss to qualify for gender-affirming bilateral breast augmentation, requiring BMI <35 kg/m2. In addition to lifestyle modification counseling, she was started on semaglutide with monthly dose escalation, leading to 13.9% weight loss with a BMI of 34.1 kg/m2 within 3 months. This case highlights the need for access to affirming weight management services for TGD patients pursuing GAS and the role of antiobesity medications in reaching presurgical BMI targets. Further studies should evaluate the needs of TGD patients in weight loss interventions and the effects of weight loss and antiobesity medications on gender-affirming hormone therapy.

Gender-affirming hormone therapy, mental health, and surgical considerations for aging transgender and gender diverse adults.

As the transgender and gender diverse (TGD) population ages, more transfeminine and transmasculine individuals present to clinic to initiate or continue their gender-affirming care at older ages. Currently available guidelines on gender-affirming care are excellent resources for the provision of gender-affirming hormone therapy (GAHT), primary care, surgery, and mental health care but are limited in their scope as to whether recommendations require tailoring to older TGD adults. Data that inform guideline-recommended management considerations, while informative and increasingly evidence-based, mainly come from studies of younger TGD populations. Whether results from these studies, and therefore recommendations, can or should be extrapolated to aging TGD adults remains to be determined. In this perspective review, we acknowledge the lack of data in older TGD adults and discuss considerations for evaluating cardiovascular disease, hormone-sensitive cancers, bone health and cognitive health, gender-affirming surgery, and mental health in the older TGD population on GAHT.

Cardiovascular disease and feminizing gender-affirming hormone therapy: Implications for the provision of safe and lifesaving care.

Sex recorded at birth, gender identity, and feminizing gender-affirming hormone therapy (fGAHT) likely contribute to cardiovascular disease (CVD) risk in transgender women. Understanding the interplay of these factors is necessary for the provision of safe, affirming, and lifesaving care. Among transgender women taking fGAHT, data show increases in CVD mortality and rates of myocardial infarction, stroke, and venous thromboembolism compared to reference populations, depending on study design and comparators. However, most studies are observational with a paucity of contextualizing information (e.g., dosing, route of administration, gonadectomy status), which makes it difficult to parse adverse fGAHT effects from confounders and interaction with known CVD risk factors (e.g., obesity, smoking, psychosocial and gender minority stressors). Increased CVD risk in transgender women points toward a need for greater attention to CVD management in this population including cardiology referral when indicated and additional research on the mechanisms and mediators of CVD risk.

Gender-affirming hormonal therapy for transgender and gender-diverse people-A narrative review.

As the number of transgender and gender-diverse (TGD) people accessing gender-affirming care increases, the need for healthcare professionals (HCPs) providing gender-affirming hormonal therapy (GAHT) also increases. This chapter provides an overview of the HCPs interested in getting involved in providing GAHT.

A Novel Multidisciplinary Model of Care for Transgender and Gender Diverse Adults: Program Description and Patient Perspectives.

Transgender and gender diverse (TGD) adults face significant health care disparities stemming from systematic discrimination and stigma in health care. We created the UCHealth Integrated Transgender Program to provide culturally responsive and clinically competent care to TGD adults in Colorado. This article outlines the clinic model and summarizes results from a qualitative patient survey to assess patients' impressions and recommendations for improvement. A multidisciplinary integrated clinic is a feasible and desired step toward improving health care for the TGD population.

Obesity Management in Cardiometabolic Disease: State of the Art.

PURPOSE OF REVIEW: To summarize research from the last 5 years on the effects of weight loss treatments, including lifestyle changes, anti-obesity medications, and bariatric procedures on cardiovascular disease (CVD) risk factors and CVD outcomes in adults. RECENT FINDINGS: This narrative review includes and summarizes the contemporary evidence of the effects of these different weight loss approaches individually. A literature search was performed using the key words obesity, weight loss, CVD, cardiometabolic, and risk factors and included key clinical trials from the past 5 years. Obesity management through weight loss is associated with improvements in CVD risk factors, such as improved blood pressure, lipid profiles, and glycemic control, with greater weight loss leading to greater improvements in CVD risk factors. Bariatric surgery is associated with greater weight loss than the other procedures and treatments for obesity, and for this, and possibly for other reasons, it is associated with greater reductions in CVD outcomes and mortality. Obesity is an independent risk factor and modulator of other CVD risk factors, and thus, treatment of obesity should be an integral part of management strategies to reduce CVD risk. Future trials and real-world studies of longer duration are needed to inform providers and patients on how to individualize the approach to modifying risks of cardiometabolic disorders through obesity management.

Routine Screening for Transgender and Gender Diverse Adults Taking Gender-Affirming Hormone Therapy: a Narrative Review.

Despite the growing number of adult transgender and gender diverse (TGD) patients seeking health services, there are many unknowns regarding how routine screening recommendations should be applied to TGD persons receiving gender-affirming hormone therapy (GAHT). Patients taking GAHT may have disease risks that differ from what is expected based on their sex assigned at birth or affirmed gender identity. We discuss two patient cases, one transgender man and one transgender woman who present for routine medical care, to review several conditions that may be impacted by the hormones utilized in masculinizing and feminizing GAHT and for which screening recommendations are available for TGD adults: cardiovascular risk factors, osteoporosis, breast cancer, cervical cancer, and prostate cancer. We reviewed the TGD-specific screening recommendations from several major medical organizations and programs and found them to be largely based upon expert opinion due to a lack of evidence. The goal of this narrative review is to assist healthcare professionals in counseling and screening their TGD patients when and where appropriate. Not all TGD adults have the ability or need to receive routine medical care from a specialized TGD health clinic; therefore, it is essential for all healthcare professionals involved in routine and gender-affirming care to have knowledge about these conditions and screenings.

Proper Care of Transgender and Gender Diverse Persons in the Setting of Proposed Discrimination: A Policy Perspective.

Transgender and gender diverse (TGD) individuals face significant barriers to accessing health care. Recent introductions of regulatory policies at state and federal levels raise concerns over the politicization of gender-affirming health care, the risks of further restricting access to quality care, and the potential criminalization of healthcare professionals who care for TGD patients. The Endocrine Society and the Pediatric Endocrine Society have published several news articles and comments in the last couple of years supporting safe and effective gender-affirming interventions as outlined in the 2017 Endocrine Society's Clinical Practice Guidelines. The Endocrine Society Position Statement on Transgender Health also acknowledges the rapid expansion in understanding the biological underpinning of gender identity and the need for increased funding to help close gaps in knowledge about the optimal care of TGD individuals. This Policy Perspective affirms these principles in the context of pending and future legislation attempting to discriminate against TGD patients while also stressing the need for science and health care experts to inform health policies.

Vaginal bleeding and spotting in transgender men after initiation of testosterone therapy: A prospective cohort study (ENIGI).

BACKGROUND: Previous studies have cross-sectionally described amenorrhea in cohorts of transgender men on intramuscular or subcutaneous testosterone injections. It remains uncertain which testosterone preparations most effectively suppress vaginal bleeding and when amenorrhea occurs after testosterone initiation. AIM: To investigate the clinical effects of various testosterone preparations on vaginal bleeding and spotting in transgender men. METHODS: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Data on the persistence and intensity of vaginal bleeding and spotting, serum sex steroid levels and body composition were prospectively and cross-sectionally assessed in 267 transgender men during a three-year follow-up period, starting at the initiation of various testosterone preparations. RESULTS: After three months of testosterone, 17.9% of transgender men reported persistent vaginal bleeding and 26.8% reported spotting. The percentages reporting vaginal bleeding and spotting decreased over the first year of testosterone (bleeding 4.7% and spotting 6.9% at 12 months, respectively), with no participants reporting vaginal bleeding or spotting after 18 months of testosterone. Factors associated with vaginal bleeding or spotting included lower serum testosterone levels and being on testosterone gel as compared to injections (e.g., esters or undecanoate preparations). If vaginal bleeding persisted, starting progestogens at three months resulted in a decrease in the intensity of vaginal bleeding and spotting. DISCUSSION: Transgender men and hormone-prescribing providers can be reassured that vaginal bleeding and spotting usually stop within three months after testosterone initiation. If not, serum testosterone levels should be measured and testosterone dose adjusted to achieve serum testosterone levels in the physiologic male range. Adding a progestin can be considered after three to six months if bleeding persists. Providers should be aware that cessation of bleeding can be more difficult to achieve in transgender men with lower serum testosterone levels or those on testosterone gel.

Early-onset Paget's disease of bone in a Mexican family caused by a novel tandem duplication (77dup27) in TNFRSF11A that encodes RANK.

Four heterozygous in-frame tandem duplications of different lengths in TNFRSF11A, the gene that encodes receptor activator of nuclear factor κB (RANK), constitutively activate RANK and lead to high turnover skeletal disease. Each duplication elongates the signal peptide of RANK. The 18-base pair (bp) duplication at position 84 (84dup18) causes familial expansile osteolysis (FEO), the 15-bp duplication at position 84 (84dup15) causes expansile skeletal hyperphosphatasia (ESH), the 12-bp duplication at position 90 (90dup12) causes panostotic expansile bone disease (PEBD), and the 27-bp duplication causes early-onset Paget's disease of bone (PDB2). The severity of the associated skeletal disease seems inversely related to the duplication's length. Additional 15- and 18-bp duplications of TNFRSF11A fit this pattern. Herein, we delineate the skeletal disease of a middle-aged man of Mexican descent who we found to harbor a novel 27-bp tandem duplication at position 77 (77dup27) of TNFRSF11A. His disorder shares features, particularly hand involvement, with the single Japanese (75dup27) and Chinese (78dup27) kindreds with PDB2 (PDB2Jpn and PDB2Chn, respectively). However, his distinct hearing loss developed later in adulthood compared to the other 27-bp families. He reported no morbidities during childhood, but in his late 20s developed unexplained tooth loss, low-trauma fractures, post-operative hypercalcemia, and painless enlargement of his fingers. Biochemical studies showed elevated serum alkaline phosphatase (ALP), bone-specific ALP, C-telopeptide, and osteocalcin consistent with rapid bone remodeling. Radiologic imaging revealed remarkably lucent bones with vertebral compression fractures, calvarial lucencies, and thinned long bone cortices. DXA showed extremely low bone mineral density. His disorder genetically and phenotypically fits best with PDB2 and can be called PDB2Mex.

Antiobesity Medication Use in 2.2 Million Adults Across Eight Large Health Care Organizations: 2009-2015.

OBJECTIVE: The aim of this study was to examine the prescribing patterns and use of antiobesity medications in a large cohort of patients using data from electronic health records. METHODS: Pharmacy- and patient-level electronic health record data were obtained on 2,248,407 adults eligible for weight-loss medications from eight geographically dispersed health care organizations. RESULTS: A total of 29,964 patients (1.3% of total cohort) filled at least one weight-loss medication prescription. This cohort was 82.3% female, with median age 44.9 years and median BMI 37.2 kg/m2 . Phentermine accounted for 76.6% of all prescriptions, with 51.7% of prescriptions being filled for ≥ 120 days and 33.8% filled for ≥ 360 days. There was an increase of 32.9% in medication days for all medications in 2015 compared with 2009. Higher prescription rates were observed in women, black patients, and patients in higher BMI classes. Of 3,919 providers who wrote at least one filled prescription, 23.8% (n = 863) were "frequent prescribers" who wrote 89.6% of all filled prescriptions. CONCLUSIONS: Weight-loss medications are rarely prescribed to eligible patients. Phentermine accounted for > 75% of all medication days, with a majority of patients filling it for more than 4 months. Less than one-quarter of prescribing providers accounted for approximately 90% of all prescriptions.

Health considerations for transgender women and remaining unknowns: a narrative review.

Transgender (trans) women (TW) were assigned male at birth but have a female gender identity or gender expression. The literature on management and health outcomes of TW has grown recently with more publication of research. This has coincided with increasing awareness of gender diversity as communities around the world identify and address health disparities among trans people. In this narrative review, we aim to comprehensively summarize health considerations for TW and identify TW-related research areas that will provide answers to remaining unknowns surrounding TW's health. We cover up-to-date information on: (1) feminizing gender-affirming hormone therapy (GAHT); (2) benefits associated with GAHT, particularly quality of life, mental health, breast development and bone health; (3) potential risks associated with GAHT, including cardiovascular disease and infertility; and (4) other health considerations like HIV/AIDS, breast cancer, other tumours, voice therapy, dermatology, the brain and cognition, and aging. Although equally deserving of mention, feminizing gender-affirming surgery, paediatric and adolescent populations, and gender nonbinary individuals are beyond the scope of this review. While much of the data we discuss come from Europe, the creation of a United States transgender cohort has already contributed important retrospective data that are also summarized here. Much remains to be determined regarding health considerations for TW. Patients and providers will benefit from larger and longer prospective studies involving TW, particularly regarding the effects of aging, race and ethnicity, type of hormonal treatment (e.g. different oestrogens, anti-androgens) and routes of administration (e.g. oral, parenteral, transdermal) on all the topics we address.