Prevalence of Multiple Causes of Death Within Young and Middle-Aged People Experiencing Sudden Cardiac Arrest.

BACKGROUND: Multiple causes of death are increasingly reported, particularly in older populations. Rates of multiple causes of young sudden death have not been quantified. METHOD: The End Unexplained Cardiac Death (EndUCD) registry was utilised to identify cases of young sudden death (aged 1-50 years) referred for forensic assessment from April 2019 to April 2022. Causes of death were coded according to whether one or more underlying causes of death were identified. Patients were compared according to the number of causes of death, with significant predictors assessed using logistic regression analysis. RESULTS: 1,085 cases of sudden death were identified. 263 (24.2%) cases had more than one competing cause of their sudden death. The most common multi-causal associations identified were dual non-cardiac causes of the sudden death (n=68), cardiomyopathy with non-cardiac event (n=64) and coronary artery disease with non-cardiac cause (n=63). Multi-causal death was more common in those undergoing comprehensive autopsy examination (95.8% vs 77.6%, p<0.0001), and in the setting of higher body mass index (median 31.3 kg/m2 vs 29.9 kg/m2, p=0.01), older age (44.3 years vs 41.4 years, p<0.0001), non-ventricular cardiac arrest rhythm (93.2% vs 87.3%, p=0.009), and smoking (22.8% vs 14.2%, p=0.001). The strongest predictor of multiple pathologies was comprehensive autopsy examination compared with external inspection, full-body post-mortem computed tomography and review of ancillary documentation and investigations (odds ratio 6.49, 95% confidence interval 3.47-12.14). CONCLUSIONS: One-quarter of young sudden deaths have more than one underlying cause, highlighting the value of comprehensive investigations including autopsy. Awareness of the complexity of young sudden death is important, along with multidisciplinary involvement to ensure all contributors to death are identified.

Gender-Affirming Hormone Therapy for the Trans, Gender Diverse, and Nonbinary Community: Coordinating World Professional Association for Transgender Health and Informed Consent Models of Care.

Purpose: Before commencing gender-affirming hormone therapy, people undergo assessments through the World Professional Association for Transgender Health (WPATH) model (typically with a mental health clinician), or an informed consent (IC) model (without a formal mental health assessment). Despite growing demand, these remain poorly coordinated in Australia. We aimed to compare clients attending WPATH and IC services; compare binary and nonbinary clients; and characterize clients with psychiatric diagnoses or longer assessments. Methods: Cross-sectional audit of clients approved for gender-affirming treatment (March 2017-2019) at a specialist clinic (WPATH model, n=212) or a primary care clinic (IC model, n=265). Sociodemographic, mental health, and clinical data were collected from electronic records, and analyzed with pairwise comparisons and multivariable regression. Results: WPATH model clients had more psychiatric diagnoses (mean 1.4 vs. 1.1, p<0.001) and longer assessments for hormones (median 5 vs. 2 sessions, p<0.001) than IC model clients. More IC model clients than WPATH model clients were nonbinary (27% vs. 15%, p=0.016). Nonbinary clients had more psychiatric diagnoses (mean 1.7 vs. 1.1, p<0.001) and longer IC assessments (median 3 vs. 2 sessions, p<0.001) than binary clients. Total psychiatric diagnoses were associated with nonbinary identities (ß 0.7, p=0.001) and health care cards (ß 0.4, p=0.017); depression diagnoses were associated with regional/remote residence (adjusted odds ratio [aOR] 2.2, p=0.011); and anxiety disorders were associated with nonbinary identities (aOR 2.8, p=0.012) and inversely associated with employment (aOR 0.5, p=0.016). Conclusion: WPATH model clients are more likely to have binary identities, mental health diagnoses, and longer assessments than IC model clients. Better coordination is needed to ensure timely gender-affirming care.

Bone Microarchitecture in Transgender Adults: A Cross-Sectional Study.

Gender-affirming hormone therapy aligns physical characteristics with an individual's gender identity, but sex hormones regulate bone remodeling and influence bone morphology. We hypothesized that trans men receiving testosterone have compromised bone morphology because of suppression of ovarian estradiol production, whereas trans women receiving estradiol, with or without anti-androgen therapy, have preserved bone microarchitecture. We compared distal radial and tibial microarchitecture using high-resolution peripheral quantitative computed tomography images in a cross-sectional study of 41 trans men with 71 cis female controls, and 40 trans women with 51 cis male controls. Between-group differences were expressed as standardized deviations (SD) from the mean in age-matched cisgender controls with 98% confidence intervals adjusted for cross-sectional area (CSA) and multiple comparisons. Relative to cis women, trans men had 0.63 SD higher total volumetric bone mineral density (vBMD; both p = 0.01). Cortical vBMD and cortical porosity did not differ, but cortices were 1.11 SD thicker (p < 0.01). Trabeculae were 0.38 SD thicker (p = 0.05) but otherwise no different. Compared with cis men, trans women had 0.68 SD lower total vBMD (p = 0.01). Cortical vBMD was 0.70 SD lower (p < 0.01), cortical thickness was 0.51 SD lower (p = 0.04), and cortical porosity was 0.70 SD higher (p < 0.01). Trabecular bone volume (BV/TV) was 0.77 SD lower (p < 0.01), with 0.57 SD fewer (p < 0.01) and 0.30 SD thicker trabeculae (p = 0.02). There was 0.56 SD greater trabecular separation (p = 0.01). Findings at the distal radius were similar. Contrary to each hypothesis, bone microarchitecture was not compromised in trans men, perhaps because aromatization of administered testosterone prevented bone loss. Trans women had deteriorated bone microarchitecture either because of deficits in microstructure before treatment or because the estradiol dosage was insufficient to offset reduced aromatizable testosterone. Prospective studies are needed to confirm these findings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Insulin resistance in transgender individuals correlates with android fat mass.

BACKGROUND: Transgender individuals receiving gender-affirming hormone therapy (GAHT) are at increased risk of adverse cardiovascular outcomes. This may be related to effects on body composition and insulin resistance. AIMS: To examine relationships between body fat distribution and insulin resistance in transgender individuals on established GAHT. METHODS: Comparisons of body composition (dual energy X-ray absorptiometry) and insulin resistance [Homeostasis Model of Insulin Resistance (HOMA2-IR)] were made between transgender individuals (43 trans men and 41 trans women) on established GAHT (>12 months) and age-matched cisgender controls (30 males and 48 females). Multiple linear regressions were used to examine the relationship between HOMA2-IR and fat mass with gender, adjusting for age and total duration of GAHT and Pearson correlation coefficients are reported. RESULTS: Compared with control cisgender women, trans men had mean difference of +7.8 kg (4.0, 11.5), p < 0.001 in lean mass and higher android:gynoid fat ratio [0.2 (0.1, 0.3), p < 0.001], but no difference in overall fat mass or insulin resistance. Compared with control cisgender men, trans women had median difference in lean mass of -6.9 kg (-10.6, -3.1), p < 0.001, fat mass of +9.8 kg (3.9, 14.5), p = 0.001, lower android:gynoid fat ratio -0.1 (-0.2,-0.0), p < 0.05), and higher insulin resistance 1.6 (1.3-1.9), p < 0.001). Higher HOMA2-IR correlated with higher android (r 2 = 0.712, p < 0.001) and gynoid (r 2 = 0.572, p < 0.001) fat mass in both trans men and trans women. CONCLUSION: Android fat more strongly correlates with insulin resistance than gynoid fat in transgender individuals. Higher fat mass and insulin resistance in trans women may predispose to increased cardiovascular risk. Despite adverse fat distribution, insulin resistance was not higher in trans men.

The Informed Consent Model of Care for Accessing Gender-Affirming Hormone Therapy Is Associated With High Patient Satisfaction.

BACKGROUND: There are 2 common approaches to assess an individual before commencing of gender-affirming hormone therapy (GAHT); a mental health practitioner assessment and approval or an informed consent model undertaken with a primary care general practitioner (GP). AIM: In a primary care clinic practising an Informed Consent Model of care to initiate GAHT, we aimed to firstly describe the proportion and characteristics of patients referred for secondary consultation to a mental health practitioner (MH referred) and secondly, we aimed to measure patient satisfaction. METHODS: A retrospective audit of all new patients with a transgender or gender diverse identity presenting to a primary care clinic in Melbourne, Australia was performed between March 2017 and March 2019. In those newly seeking GAHT, de-identified data were obtained including presence of secondary mental health practitioner referral, time to GAHT commencement and co-occurring mental health conditions. A separate survey assessed patient satisfaction. OUTCOMES: Mental health conditions and overall patient satisfaction in those referred for secondary mental health consultation (MH referred) were compared with those who were not (GP assessed). RESULTS: Of 590 new consultations, 309 were newly seeking GAHT. Referrals for secondary mental health assessment before GAHT occurred in 8%. The GP-assessed group commenced GAHT at median 0.9 months (0.5-1.8) after initial consultation compared with 3.1 months (1.3-4.0), P < .001 in the MH-referred group. The MH-referred group was more likely to have post-traumatic stress disorder (adjusted P = .036) and schizophrenia (adjusted P = .011). Of 43 respondents to the survey, a higher proportion in the GP-assessed group was extremely satisfied with their overall care compared with the MH-referred group (P < .01). Notably, 80% in the GP-assessed group chose to seek mental health professional support. CLINICAL IMPLICATIONS: Initiation of GAHT can be performed in primary care by GPs using an informed consent model and is associated with high patient satisfaction. Mental health professionals remain a key source of support. STRENGTHS & LIMITATIONS: This retrospective audit did not randomize patients to pathways to initiate GAHT. Follow-up duration was short. Responder bias to survey with low response rates may overestimate patient satisfaction. This is one of the first studies to evaluate an informed consent model of care. CONCLUSION: More widespread uptake of an informed consent model of care to initiate GAHT by primary care physicians has the potential for high patient satisfaction and may be a practical solution to reduce waiting lists in gender clinics. Spanos C, Grace JA, Leemaqz SY, et al. The Informed Consent Model of Care for Accessing Gender-Affirming Hormone Therapy Is Associated With High Patient Satisfaction. J Sex Med 2021;18:201-208.

Effects of gender-affirming hormone therapy on insulin resistance and body composition in transgender individuals: A systematic review.

BACKGROUND: Transgender individuals receiving masculinising or feminising gender-affirming hormone therapy with testosterone or estradiol respectively, are at increased risk of adverse cardiovascular outcomes, including myocardial infarction and stroke. This may be related to the effects of testosterone or estradiol therapy on body composition, fat distribution, and insulin resistance but the effect of gender-affirming hormone therapy on these cardiovascular risk factors has not been extensively examined. AIM: To evaluate the impact of gender-affirming hormone therapy on body composition and insulin resistance in transgender individuals, to guide clinicians in minimising cardiovascular risk. METHODS: We performed a review of the literature based on PRISMA guidelines. MEDLINE, Embase and PsycINFO databases were searched for studies examining body composition, insulin resistance or body fat distribution in transgender individuals aged over 18 years on established gender-affirming hormone therapy. Studies were selected for full-text analysis if they investigated transgender individuals on any type of gender-affirming hormone therapy and reported effects on lean mass, fat mass or insulin resistance. RESULTS: The search strategy identified 221 studies. After exclusion of studies that did not meet inclusion criteria, 26 were included (2 cross-sectional, 21 prospective-uncontrolled and 3 prospective-controlled). Evidence in transgender men suggests that testosterone therapy increases lean mass, decreases fat mass and has no impact on insulin resistance. Evidence in transgender women suggests that feminising hormone therapy (estradiol, with or without anti-androgen agents) decreases lean mass, increases fat mass, and may worsen insulin resistance. Changes to body composition were consistent across almost all studies: Transgender men on testosterone gained lean mass and lost fat mass, and transgender women on oestrogen experienced the reverse. No study directly contradicted these trends, though several small studies of short duration reported no changes. Results for insulin resistance are less consistent and uncertain. There is a paucity of prospective controlled research, and existing prospective evidence is limited by small sample sizes, short follow up periods, and young cohorts of participants. CONCLUSION: Further research is required to further characterise the impact of gender-affirming hormone therapy on body composition and insulin resistance in the medium-long term. Until further evidence is available, clinicians should aim to minimise risk by monitoring cardiovascular risk markers regularly in their patients and encouraging healthy lifestyle modifications.