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The Occurrence of Acute Cardiovascular Events in Transgender Individuals Receiving Hormone Therapy: Results from a Large Cohort Study
Abstract
In hypogonadal/postmenopausal individuals, hormone therapy has been associated with an increased risk for cardiovascular events (CVEs). A steeply growing population that often receives exogenous hormones is transgender individuals. Although transgender individuals hypothetically have an increased risk of CVEs, there is little known about the occurrence of CVEs in this population.1 Therefore, we determined the incidences of acute/spontaneous strokes (ischemic/hemorrhagic, transient ischemic attack, or subarachnoid hemorrhage), myocardial infarctions (MIs), and venous thromboembolic events (VTEs) in transwomen and transmen receiving transgender hormone therapy (THT). Subsequently, we compared these incidences with those reported in women and men from the general population.
... However, it is important to have patient-provider discussions summarizing the available data on long-term outcomes related to GAHT and routes of administration. For example, feminizing GAHT (ie, estrogen plus antiandrogen) has been associated with increased risk of venous thromboembolism (VTE), ischemic stroke, and myocardial infarction compared with the general population, depending on estrogen formulation, cohort, and comparison group (9,10). Masculinizing GAHT (ie, testosterone) does not appear to have similar risk of cardiovascular outcomes as feminizing GAHT, but a recent study showed an increased risk for myocardial infarction among transgender men as compared with cisgender women (10). ...
... For example, feminizing GAHT (ie, estrogen plus antiandrogen) has been associated with increased risk of venous thromboembolism (VTE), ischemic stroke, and myocardial infarction compared with the general population, depending on estrogen formulation, cohort, and comparison group (9,10). Masculinizing GAHT (ie, testosterone) does not appear to have similar risk of cardiovascular outcomes as feminizing GAHT, but a recent study showed an increased risk for myocardial infarction among transgender men as compared with cisgender women (10). Regarding bone health, low bone mineral density (BMD) has been seen in TGD patients prior to GAHT initiation and after patients stop GAHT post-gonadectomy, but long-term feminizing and masculinizing GAHT are associated with at least maintenance of BMD (11,12). ...
... cisgender women and 4.55 compared with cisgender men (10). The standardized incidence ratios decreased slightly to 3.92 and 3.39, respectively, in a subgroup analysis excluding transgender women who initiated GAHT before 2001 (after which ethinyl estradiol was no longer used). ...
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 two adults with thromboembolic disease and two adults with low bone mineral density in the setting of feminizing and masculinizing GAHT.
... 47 Furthermore, due to their pharmacodynamic properties, estradiol and testosterone preparations both have the potential to increase cardiovascular disease risk and events. 46,48,49 To ensure the safe administration of GAHT, pharmacists must be aware of which formulations are associated with higher cardiovascular risks and provide recommendations for minimizing those effects. ...
... However, mixed cohorts of TGD individuals with and without evidence of receiving GAHT have been compared to cisgender populations. 46,48,50 One study found that transgender men have nearly a 5-fold increased risk for MI compared to cisgender women and a 2-fold increased risk compared to cisgender men. Transgender women were associated with over a 2-fold increased risk of MI compared to cisgender women. ...
... However, this study did not account for other cardiovascular risk factors (e.g., smoking, hypertension). 48 In a large retrospective study, transgender women receiving estrogen had approximately twice the risk of ischemic stroke compared to cisgender women, but no difference was observed for cisgender men. 49 Moreover, as the follow-up period increased from 2 to 8 years, the risk of ischemic stroke in transgender women also steadily increased. ...
Background:
Transgender and gender-diverse (TGD) individuals in the United States (U.S.) face healthcare disparities compounded with discrimination and limited access to necessary medical services. Gender-affirming interventions have been shown to mitigate gender dysphoria and psychiatric comorbidities, yet U.S. legislation limiting such interventions has increased. As medication experts, pharmacists can facilitate access to care and appropriate use of gender-affirming hormone therapy (GAHT) and educate other healthcare providers on best practices for caring for TGD individuals in a variety of settings.
Objectives:
To provide pharmacists with a contemporary review of GAHT and associated medication-related concerns.
Methods:
We searched PubMed for articles published until December 2022. MeSH terms such as transgender, transsexual, gender diverse, gender variant, or gender non-conforming in combination with phrases like gender-affirming care, treatment, pharmacotherapy, or hormone therapy were used to capture desired articles.
Results:
Feminizing hormone therapy (FHT), such as estrogen and anti-androgen agents, increases female secondary sex characteristics while suppressing male secondary sex characteristics. Masculinizing hormone therapy (MHT) achieves male secondary sex characteristics and minimizes female secondary sex characteristics using testosterone. For both FHT and MHT, the choice of therapy and formulation ultimately involves the patient's treatment goals, preferences, and tolerability. GAHT has additional health considerations pertaining to renal drug dosing, fertility, cardiovascular, and cancer risks. Pharmacists may provide crucial guidance and education to both patients and healthcare providers regarding risks associated with GAHT.
Conclusion:
Many pharmacists feel unprepared to help provide, manage, and optimize GAHT. For many TGD individuals, GAHT is medically necessary and a life-saving treatment. Therefore, pharmacists should be provided tools to close knowledge gaps and improve their ability to care for these patients. By offering a thorough updated overview of GAHT, pharmacists can gain confidence to provide appropriate care for this increasingly visible population.
... Coagulation Markers In transgender women, GAHT resulted in procoagulant changes, including increased levels of Factors IX and XI and decreased levels of protein C, 11,17 which likely contribute to the increased rates of venous thromboembolism (VTE) observed in these individuals. 11, [18][19][20] Insulin Resistance A systematic review of estrogen therapy in transgender women reported that 5 of 8 studies included showed increased insulin resistance, with 3 finding no effect. 11, 21 Another study showed that insulin sensitivity and incretin responses after an oral glucose tolerance test decreased with estrogen treatment. ...
... 19 Nota et al reported the results of a large cohort study (n=2,517 transgender women with GAHT; median age 30 years). 20 The mean and median follow-up durations were 9.07 and 5.95 years, respectively. Incidence ratios for VTE and stroke were significantly higher for transgender women than for reference people ( Table 3). ...
... 19 Nota et al reported the results of a large cohort study of 1,358 transgender men with hormone therapy (median age 23 years), with a mean and median follow-up duration of 8.10 and 4.10 years, respectively. 20 In that study, transgender men had a 3.69fold higher risk of MI than reference cisgender women ( Table 3), but no increased risk of stroke or VTE compared with reference cisgender women and reference cisgender men. 20 In the ENIGI study, which prospectively evaluated 165 transgender men (mean age 26.78 years) over a 2-year follow-up after testosterone administration, the cardiovascular risk was calculated according to the Framingham 30-year cardiovascular risk estimate. ...
Gender-affirming hormone treatment generally by cross-sex hormones is an important strategy for transgender people to achieve the physical features affirming their experienced gender. Estrogens and androgens are administrated, usually for a long time, to transgender women and transgender men who would like to physically achieve feminization and masculinization, respectively. Several harmful adverse events have been reported in the literature following the administration of gender-affirming hormones, including worsening of lipid profiles and cardiovascular events (CVE) such as venous thromboembolism, stroke, and myocardial infarction, but it remains unknown whether the administration of cross-sex hormones to transgender people increases the subsequent risk of CVE and death. Based on the findings of the present narrative review of the recent literature, including meta-analyses and relatively large-scale cohort studies, it is likely that estrogen administration increases the risk of CVE in transgender women, but it remains inconclusive as to whether androgen administration increases the risk of CVE in transgender men. Thus, definitive evidence guaranteeing the long-term safety of cross-sex hormone treatment on the cardiovascular system is insufficient because of lack of evidence from well-organized, high-quality, and large-scale studies. In this situation, as well as considering the proper use of cross-sex hormones, pretreatment screening, regular medical monitoring, and appropriate intervention for risk factors of CVE are necessary to maintain and improve the health of transgender people.
... 6 Cohort studies have reported increased CV risk and mortality in transgender women receiving GAHT, especially when compared with cisgender women. [6][7][8] However, due to their retrospective design, these studies present limitations related to potential confounders and missing data, as aging and preexisting CV risk factors may have contributed to the increased risk. Moreover, the widespread use of ethinyl estradiol (EE) until about 2003 may have influenced the increase in CV risk observed in trans women. ...
... Moreover, the widespread use of ethinyl estradiol (EE) until about 2003 may have influenced the increase in CV risk observed in trans women. 7 Studies of trans men receiving GAHT report no increased risk of cardiovascular disease (CVD) compared with the general population, 6,8 except for a large cohort study by Nota et al, 7 who found that trans men are at higher risk of myocardial infarction than reference women. ...
... Moreover, the widespread use of ethinyl estradiol (EE) until about 2003 may have influenced the increase in CV risk observed in trans women. 7 Studies of trans men receiving GAHT report no increased risk of cardiovascular disease (CVD) compared with the general population, 6,8 except for a large cohort study by Nota et al, 7 who found that trans men are at higher risk of myocardial infarction than reference women. ...
Objective:
The impact of gender-affirming hormone therapy (GAHT) on cardiovascular health is still not entirely established. A systematic review was conducted to summarize the evidence on the risk of subclinical atherosclerosis in transgender people receiving GAHT.
Methods:
A systematic review was performed following PRISMA guidelines, and data were searched in PubMed, LILACS, EMBASE, and Scopus databases for cohort, case-control, and cross-sectional studies or randomized clinical trials, including transgender people receiving GAHT. Transgender men and women before and during/after GAHT for at least 2 months, compared with cisgender men and women or hormonally untreated transgender persons. Studies reporting changes in variables related to endothelial function, arterial stiffness, autonomic function, and blood markers of inflammation/coagulation associated with cardiovascular risk were included.
Results:
From 159 potentially eligible studies initially identified, 12 were included in the systematic review (8 cross-sectional and 4 cohort studies). Studies of trans men receiving GAHT reported increased carotid thickness, brachial-ankle pulse wave velocity (baPWV), and decreased vasodilation. Studies of trans women receiving GAHT reported decreased IL-6, PAI-1 and tPA levels and baPWV, with variations in FMD and arterial stiffness depending on the type of treatment and route of administration.
Conclusions:
The results suggest that GAHT is associated with an increased risk of subclinical atherosclerosis in transgender men but may have either neutral or beneficial effects in transgender women. The evidence produced is not entirely conclusive, suggesting that additional studies are warranted in the context of primary prevention of cardiovascular disease in the transgender population receiving GAHT.
... Transwomen (persons born with male sex and female gender identity) who use gender-affirming hormone therapy (typically estrogen with antiandrogens) seem to have an increased risk of both venous and arterial thrombotic events compared with control cismen (persons born with male sex assigned at birth and a male gender identity). [31][32][33][34][35] When comparing coagulation profiles before and after start of hormone therapy in these persons, the coagulation profiles were overall more procoagulant after the start of hormone therapy. 36 On the risk of venous and arterial thrombotic events in transmen (persons born with female sex assigned and male gender identity) who use testosterone as gender-affirming hormone therapy, only few data are available. ...
... 36 On the risk of venous and arterial thrombotic events in transmen (persons born with female sex assigned and male gender identity) who use testosterone as gender-affirming hormone therapy, only few data are available. 31,[33][34][35] In the available studies, there does not seem to be an increased risk of thrombotic events compared with control ciswomen (persons born with female sex assigned at birth and a female gender identity). 31,33,34 In line with this, the overall coagulation profiles of transmen after start of testosterone therapy did not appear more procoagulant than before start of therapy. ...
... 31,[33][34][35] In the available studies, there does not seem to be an increased risk of thrombotic events compared with control ciswomen (persons born with female sex assigned at birth and a female gender identity). 31,33,34 In line with this, the overall coagulation profiles of transmen after start of testosterone therapy did not appear more procoagulant than before start of therapy. 36 Taken together, these observations suggest that use of exogenous estrogens (frequently combined with progestogens) results in procoagulant changes and increased VTE risk in both women and persons with male sex assigned at birth. ...
Men seem to have a higher intrinsic risk of venous thromboembolism (VTE) than women, regardless of age. To date, this difference has not been explained. By integrating state‐of‐the‐art research presented at the International Society on Thrombosis and Haemostasis Congress of 2021 with the available literature, we address potential explanations for this intriguing risk difference between men and women. We discuss the role of exogenous and endogenous sex hormones as the most important known sex‐specific determinants of VTE risk. In addition, we highlight clues on the role of sex hormones and VTE risk from clinical scenarios such as pregnancy and the polycystic ovary syndrome. Furthermore, we address new potential sex‐specific risk factors and unanswered research questions, which could provide more insight in the intrinsic risk difference between men and women, such as body height and differences in body fat distribution, leading to dysregulation of metabolism and inflammation.
... De Blok et al. 9 evaluaron este aspecto en adultos transgénero entre 1972 y 2018, y encontraron que 10 de 1641 individuos transmasculinos (edad media: 23 años; rango intercuartílico [IQR]: 20-32) murieron de ECV; tampoco hubo diferencias en la mortalidad relacionada con ECV cuando se comparó con la población en general, hombres y mujeres. Respecto a eventos cardiovasculares, Nota et al. 10 describieron tasas estandarizadas de incidencia no significativas (SIR) para tromboembolia venosa y EVC isquémico en adultos transmasculinos comparados con la población en general, hombres y mujeres. Sin embargo sí se observó una SIR significativamente más alta para infarto del miocardio entre 1358 adultos transmasculinos (edad media: 23 años) comparados con la población en general de mujeres (3.69; intervalo de confianza del 95% [IC95%]: 1.94-6.42), ...
... Cabe destacar que un análisis por subgrupos para mortalidad por todas las causas que solo incluyó adultas transfemeninas que tomaron etinilestradiol mostró unas SMR similares a las de la cohorte completa. Respecto a eventos cardiovasculares, Nota et al. 10 Las personas adultas transfemeninas tuvieron una incidencia más alta de infarto al miocardio al ser comparada con la de la población general de mujeres (SIR: 2.64; IC95%: 1.81-3.72), pero no en comparación con los hombres (SIR: 0.79; IC95%: 0.54-1.11). ...
Resumen
Este artículo resume la literatura existente hasta este momento sobre el impacto de la terapia hormonal para la asignación de género utilizada en la población transgénero, y de los factores de riesgo tradicionales y emergentes, en los desenlaces cardiovasculares o los marcadores subrogados de enfermedad cardiovascular. Actualmente se reconoce la evidencia creciente de que las personas transgénero o con género diverso son víctimas de disparidades en una gran variedad de factores de riesgo cardiovascular comparadas con sus pares cisgénero. Se ha reportado disparidad en morbilidad y mortalidad como resultado de una alta prevalencia en estilos de vida no saludables. Sin embargo, recientemente se ha incorporado la interpretación de que no solo la disparidad en factores de riesgo cardiovascular es lo que incrementa el riesgo en la salud cardiovascular de la población transgénero. Existe la hipótesis de que el exceso en morbilidad y mortalidad cardiovascular está relacionado con estresores psicosociales a lo largo de la vida de este grupo en múltiples niveles, incluyendo violencia estructurada (p. ej., discriminación, falta de acceso a los servicios de salud, falta de vivienda digna, etc.). La falta de información y de investigación en este grupo son limitantes importantes que requieren un abordaje multifacético para mejorar aspectos como la promoción de la salud y el mejor cuidado cardiovascular.
... MTF individuals have increased mortality compared with age-matched cis subjects, whereas FTM individuals have similar mortality as age-matched cis subjects [7]. Since data linking testosterone-based gender-affirming hormone therapy (GAHT) for FTM individuals to heightened thrombosis risk are weaker and controversial, we focus herein on MTF individuals [8][9][10][11][12][13]. To care appropriately for these patients, further understanding of mechanisms leading to GAHT-associated thrombosis, as well as better ability to detect thrombotic risk, are needed. ...
... In contrast to the Belgian cohorts, the United States cohort's hazard ratios were significantly greater than that of cis men and women at 8-year follow-up (16.7 and 13.7, respectively) compared with 2-year follow-up (4.1 and 3.4, respectively), suggesting an inflection point of increased venous thromboembolism risk around 2 years of follow-up [9]. A study from the Netherlands found that trans women using GAHT have a significantly increased standardized incidence ratio of venous thromboembolism compared with both cis men and cis women (4.55 and 5.52, respectively) across 22,830 total years of follow-up [13]. Notably however, several of these studies did not control for co-existing risk factors that may inflate risk (eg, smoking), which may account for differences in cumulative risk estimates. ...
Gender-affirming hormonal therapies are a critical component of the care of transgender individuals. Transgender people are commonly prescribed estrogen or testosterone to promote male-to-female or female-to-male transitions and to preserve gender-specific characteristics long-term. However, some exogenous hormones, especially certain estrogen preparations, are an established risk factor of thrombosis. As the number of individuals seeking gender-based care is rising, there is an urgent need to identify and characterize the mechanisms underlying hormone-associated thrombosis and incorporate this information into clinical algorithms for diagnosis and management. Herein, we discuss historical evidence on the incidence of thrombosis and changes in plasma composition in transgender and cisgender cohorts. We present 3 case studies to demonstrate knowledge gaps in thrombosis risk stratification and prediction tools. We also present data from in vitro coagulation and fibrinolysis assays and discuss how information from these kinds of assays may be used to help guide the clinical management of transgender individuals.
... This induces lowered voice, body and facial hair growth, menstrual cessation, as well as changes in body composition (increase in muscle mass and reduction in fat mass) (26,29,30). Common risks include acne, unmasking polycythemia (particularly in the setting of other conditions such as sleep apnea), infertility, androgenic alopecia, hypertension, reduced high-density lipoprotein cholesterol and an increased risk of myocardial infarction relative to cisgender women (26,31). ...
... Voice pitch and skeletal size do not change (26,29,30). Adverse effects include an increased risk of venous thromboembolism, infertility, weight gain, and hypertriglyceridemia as well as elevated risk of myocardial infarction and stroke relative to cisgender women and men in the setting of additional risk factors (26,30,31,34). ...
Context:
The inclusion of transgender people in elite sport has been a topic of debate. This narrative review examines the impact of gender affirming hormone therapy (GAHT) on physical performance, muscle strength and markers of endurance.
Evidence acquisition:
MEDLINE and Embase were searched using terms to define the population (transgender), intervention (GAHT) and physical performance outcomes.
Evidence synthesis:
Existing literature is comprised of cross-sectional or small uncontrolled longitudinal studies of short duration. In non-athletic trans men starting testosterone therapy, within 1 year, muscle mass and strength increased, and by 3 years, physical performance (push-ups, sit-ups, run time) improved to the level of cisgender men.In non-athletic trans women, feminising hormone therapy increased fat mass by approximately 30% and decreased muscle mass by approximately 5% after 12 months and steadily declined beyond 3 years. Whilst absolute lean mass remains higher in trans women, relative percentage lean mass and fat mass (and muscle strength corrected for lean mass), hemoglobin and VO2 peak corrected for weight was no different to cisgender women. After 2 years of GAHT, no advantage was observed for physical performance measured by running time or in trans women. By 4 years, there was no advantage in sit-ups. Whilst push-ups performance declined in trans women, a statistical advantage remained relative to cisgender women.
Conclusions:
Limited evidence suggests that physical performance of non-athletic trans people who have undergone GAHT for at least 2 years approaches that of cisgender controls. Further controlled longitudinal research is needed in trans athletes and non-athletes.
... However, barriers to receiving culturally competent transgender care were previously reported in a 2015 representative survey of endocrinologists (16). Similar to cisgender women, there is a paucity of high-quality data because of a shortage of RCTs about the effects of TTh on CVD among transgender people, with 2 European studies reporting an increased risk of CVD and CVD mortality among them (14,17), but not other studies (18,19). Therefore, the objectives of this study are to investigate the effects of TTh on a composite CVD outcome, and its specific disease outcomes, in women and transgender people (≥30 years), and to determine whether these effects vary by age groups of pre-and postmenopausal status. ...
... Although our study has a large sample size of CVD cases among transgender people (n = 273), similar to the previous meta-analyses, we were still limited to provide a definite conclusion. Recently, 2 European retrospective cohort studies reported an increased risk of CVD (stroke observed cases, n = 35; MI observed cases, n = 41) (17) and CVD mortality (CVD deaths, n = 50 transgender women; CVD deaths, n = <10 transgender men) (14) among transgender people. We also conducted a retrospective cohort study, yet our findings with a transgender population were not significant, and it is possible that this is because we could not differentiate between the transgender population (transgender males and females). ...
Aims:
This study aimed to investigate the association of testosterone replacement therapy (TTh) with risk of cardiovascular disease (CVD), and CVD-specific outcomes, in cisgender women and transgender population, and to determine whether this association varies by menopausal status.
Methods:
In 25,796 cisgender women and 1,580 transgender people (≥ 30 yrs old), who were enrolled in the Optum's de-identified Clinformatics® Data Mart Database (2007-2021), we identified 6288 pre- and post-menopausal cisgender women and 262 transgender people diagnosed with incident composite of CVD (coronary artery disease [CAD], congestive heart failure [CHF], stroke, myocardial infarction). Pre-diagnostic prescription of TTh was ascertained for this analysis. Multivariable adjusted Cox proportional hazards models were used to examine the independent association of TTh with incident CVD.
Results:
We found a 24% increased risk of CVD (HR = 1.24, 95% CI: 1.15, 1.34), 26% risk of CAD (HR = 1.26, 95% CI: 1.14, 1.39) and a 29% risk of stroke (HR = 1.29, 95% CI: 1.14, 1.45) after comparing cisgender women who used TTh with non-users. Stratification by age group showed similar effects of TTh on CVD, CAD and stroke. Among transgender people, TTh did not increase the risk of composite CVD, including by age stratification.
Conclusion:
Use of TTh increased the risk of CVD, CAD and stroke among is cisgender women, but not among transgender people. TTh is becoming more widely accepted in women, and it is the main medical treatment for transgender males. Therefore, use of TTh should be further investigated for the prevention of CVD.
... The use of testosterone therapy may alter a patient's cardiovascular risk factors. Nota et al. 27 found no associated increased in venous thromboembolism (VTE), myocardial infarction (MI) or stroke in trans men when compared to cis men. When compared to baseline incidence in cis women, taking testosterone therapy was associated with an increase in risk of MI (standardised incidence ratio of 3.69), but no increased risk of VTE or stroke. ...
... After 6 months of hormone therapy, it is acceptable to calculate a patient's creatinine clearance and IBW based on the patient's affirmed gender. 27 This general guidance will also apply to use of total intravenous anaesthesia (TIVA). All pharmocokinetic models require a programmed gender for the patient, and we know that lean body mass will start to resemble that of the affirmed gender at around 3 months of hormone therapy. ...
As clinicians working in critical care, it is our duty to provide all of our patients with the high-quality care they deserve, regardless of their gender identity. The transgender community continues to suffer discrimination from the media, politicians and general public. As healthcare workers we often pride ourselves on our ability to safely care for all patients. However, there remains a distinct lack of understanding surrounding the care of critically ill transgender patients. This is likely in part because the specific care of transgender patients is not included in the Faculty of Intensive Care Medicine’s, Royal College of Anaesthetists’, Royal College of Physician’s, or Royal College of Emergency Medicine’s curriculum. There are several important considerations relevant for transgender patients in critical care including anatomical changes to the airway, alterations to respiratory and cardiovascular physiology and management of hormone therapy. Alongside this, there are simple but important social factors that exist, such as the use of patient pronouns and ensuring admittance to correctly gendered wards. In this review we will address the key points relevant to the care of transgender patients in critical care and provide suggestions on how education on the subject may be improved.
... The specific risks associated with hormonal therapy in transgender patients are still being elucidated. Nota et al (2019) have amassed one of the largest bodies of data on the subject. The risk rate of stroke, myocardial infarction and venous thromboembolism in transgender patients, compared to their cisgender counterparts, are summarised in Table 2 (Nota et al, 2019). ...
... Nota et al (2019) have amassed one of the largest bodies of data on the subject. The risk rate of stroke, myocardial infarction and venous thromboembolism in transgender patients, compared to their cisgender counterparts, are summarised in Table 2 (Nota et al, 2019). ...
Recent years have seen an increase in the number of people openly identifying as transgender in the UK, with current estimates ranging between 200 000 and 600 000 individuals. There has also been an increase in the number of patients undergoing both medical and surgical gender-affirming treatment. There are several important, specific considerations that perioperative clinicians must be aware of when caring for transgender patients, including changes to the airway, potential respiratory and cardiovascular complications, and the management of hormone therapy. Alongside this, important general considerations include the correct use of patient pronouns and ensuring patients are admitted to correctly gendered wards. Despite the need for these considerations, the perioperative management of transgender patients is not covered in the Royal College of Anaesthetists' curriculum; to date, no national guidelines exist on the subject. This article discusses some of the key, specific perioperative considerations relevant to transgender patients, and highlights the need for national guidelines and improved education on the subject.
... 4 However, data about long-term effects on safety of hormone treatments are scarce, leading to insufficient evidence to determine long-term safety, especially regarding cancer and hormone-sensitive cancers specifically, as well as cardiovascular disease. Previous studies have showed an increased risk of strokes, 5,6 myocardial infarctions, 5 and venous thromboembolisms 5,6 among transgender women who received hormone treatment. In transgender men who received testosterone treatment, an increased risk of myocardial infarctions was described. ...
... In transgender men who received testosterone treatment, an increased risk of myocardial infarctions was described. 5 Furthermore, transgender women using long-term, high dose cypro terone acetate (a progestogenic antiandrogen) might have a higher risk of meningioma than do general population women and general population men. 7 Whether hormone treatment increases the risk of cancer in general and hormonesensitive cancer specifically has not yet been fully established. ...
... Long-term cardiovascular and metabolic health in transgender study populations has been discussed, especially the possible impact of GAHT on health outcomes (3,6). Changes in sex hormone levels during transition in transgenders may increase the risk of cardiovascular disease (7,8,9,10,11). Cardiovascular morbidity in transgender men could be converted from female phenotype to resemble the risk of age-matched male controls and vice versa for transgender women; however, also the birthassigned sex could be important for long-term morbidity (11,12,13). ...
... Short follow-up duration and limited number of cardiovascular events in transgender study cohorts is a limitation in all studies due to expansion of transgender care, especially within the last decade (6,9,43). Higher cardiovascular risk in transgenders is supported by recent studies in selected study cohorts (6,8,9). Our finding of HR for CVD ranged from 1.63 to 2.20 in transgenders corresponded to recent prospective and cross-sectional studies in transgender study cohorts (6,7,10,43). ...
Background: Cardiovascular risk could be increased in transgender persons, but the mechanism is undetermined.
Aim: To assess the risk of cardiovascular outcomes in Danish transgender persons compared to controls.
Methods: Historical register-based cohort study in Danish transgender persons and age-matched controls. The main outcome measure was cardiovascular diagnosis (any CVD) including medicine prescriptions for CVD during 2000-2018. The transgender cohort (N=2671) included persons with ICD-10 diagnosis code of “gender identity disorder” (N=1583) and persons with legal sex change (N=1088), 1270 were assigned female at birth (AFAB) and 1401 were assigned male at birth (AMAB). Controls (N=26,710) were matched by age (n=5 controls of same and n=5 controls of other birth sex) of their respective transgender person.
Results: The median (interquartile range) age at study inclusion was 22 (18; 29) years for persons AFAB and 26 (21; 39) years for persons AMAB, The mean (SD) follow up time was 4.5 (4.2) years for persons AFAB and 5.7 (4.8) years for persons AMAB. The hazard ratio (HR) for any CVD was significantly higher in transgender persons vs controls of same and other birth sex, with highest adjusted HR in transgender persons AFAB vs control men: 2.20 (95% CI: 1.64;2.95), p<0.00. Gender affirming hormone treatment (GAHT) explained part of elevated risk of CVD in transgender persons AFAB, whereas GAHT did not contribute to the elevated risk of CVD in transgender persons AMAB.
Conclusions: The risk of cardiovascular diagnosis was increased in transgender persons. The mechanism should be further investigated.
... Studies that have evaluated physical health disparities that exist among transgender adults have found increased risk of cardiovascular disease among transgender adults [8,9]. Most of these studies have focused on HIV [10][11][12], substance use [13][14][15], and hormone use [16][17][18][19] without significant emphasis on specific vascular disease mechanisms and outcomes. Many of these risk factors may also lead to increased risk for cerebrovascular disease. ...
... A retrospective medical chart review of 2517 transwomen and 1358 transmen who visited a gender clinic in the Netherlands from 1972 to 2015 found that those taking hormone therapy had higher incidences of stroke and venous thromboembolic events as compared to reference cismen and ciswomen [18]. Both transwomen and transmen taking hormone therapy were found to have higher risk of myocardial infarction than reference ciswomen. ...
Purpose of Review
To identify the current state of science on stroke in transgender adults and highlight gaps in need of further research. We will review current research on cerebrovascular risk and disease, hormone therapy, and stroke in transgender individuals. Finally, we will provide a framework for healthcare providers to prevent and reduce disparities through inclusive care practices.
Recent Findings
Transgender people experience unique stroke risk factors, secondary to both psychosocial stress and health-related behaviors. These include higher rates of HIV, tobacco use, stimulant use, and hepatitis C. The use of gender-affirming hormone therapy may lead to an increased risk for ischemic stroke, but the data are limited and require further research.
Summary
Recent research has highlighted the numerous healthcare disparities faced by transgender individuals. Regarding stroke disparities, these are multifactorial and include contributions from health-related behaviors, inadequate access to care, the use of hormonal therapy, and minority stress. Further research is needed to increase access to care and reduce the substantial gap in outcomes for these individuals.
... In a study of 3875 Dutch transgender adults receiving GAHT, both transgender women and transgender men had higher incidence of MI compared to cisgender women but were similar when compared to cisgender men [36]. While this study did not evaluate for cardiovascular risk factors, a Kaiser study that controlled for certain cardiovascular risk factors such as tobacco use, blood pressure, cholesterol level, and BMI reported similar results for transgender women on GAHT [37]. ...
... Transgender men did not have higher risks of stroke compared to cisgender men or women. In studies where utilization of GAHT was confirmed, transgender women receiving GAHT were again found to have higher incidence of stroke compared to cisgender cohorts [36,37]. ...
Purpose of Review
Transgender individuals represent a growing part of our population with current trends indicating that clinicians will be treating more transgender patients in both the inpatient and outpatient setting. Current cardiovascular guidelines lack recommendations for transgender care secondary to limited data in this population. As we await future guideline recommendations, we provide a comprehensive review of the literature and practical management strategies related to transgender cardiovascular health.
Recent Findings
Transgender individuals are at higher risk for some cardiovascular diseases compared to their cisgender counterparts. Gender-affirming hormone therapy, concomitant health conditions, lifestyle habits, access to services, and quality of care all contribute to this finding.
Summary
While it is likely both safe and appropriate to apply current CVD guidelines to the care of transgender men and women, clinicians should consider additional factors in risk assessment and address unique aspects of care at every visit.
... Moreover, transgender people face health care challenges related to medical gender transition. Gender-affirming medical procedures may be related to a range of side effects [25,26]. Medical transition (transitioning and endocrine or surgical gender-affirming medical procedures) is commonly accepted as an effective treatment for gender dysphoria and is associated with transgender individuals' mental health [14]. ...
Background:
Transgender people face significantly greater discrimination and health disparities in health care settings than cisgender people. The role of education in eliminating this phenomenon has been increasingly recognized by many medical schools. However, transgender health content is sparse or lacking in the medical curricula of many countries.
Method:
This study was designed to validate the Greek version of the Transgender Attitudes and Beliefs Scale (TABS-Gr). The study adopted a cross-sectional, comparative-descriptive research design. Participants (N = 203) were contacted through online recruitment and invited to complete an anonymous web-based survey. The data were collected between December 2022 and February 2023.
Results:
The overall reliability of the TABS-Gr questionnaire was high (Cronbach's α = 0.961, p. from Hotelling's T-squared test < 0.000). High Cronbach's alpha values were estimated for the three subscales, with α = 0.958 for Interpersonal Comfort, α = 0.906 for Gender Beliefs, and α = 0.952 for Human Values. Hotelling's T-squared test confirmed that all items on the scale had the same mean (p < 0.001 for all subgroups). Explanatory factor analysis (EFA) demonstrated adequate fit. Convergent and discriminant validity were validated based on the estimated correlations. The three-factor structure of the Greek TABS version was confirmed. The mean total score was 155.95 (SD = 30.63), indicating that medical students had a moderately positive attitude towards transgender people. Participants showed significantly less biased (more tolerant, positive) attitudes towards transgender people on the Interpersonal Comfort (IC) and Human Value (HV) subscales than on the Sex/Gender Beliefs (SGB) subscale. A demographic comparison was conducted and demonstrated a correlation between scores and sociodemographics, except for place of origin. A statistically significant increase in the total mean score was estimated for women compared to men.
Conclusion:
The overall psychometric findings provide some evidence to support the validity of the Greek version of the TABS. However, we call for further validation research in Greek medical schools. Since our claims for validity are based in part on an exploratory factor analysis, a future confirmatory factor analysis (CFA) is part of our call for further validation research. While the results of this study are mostly in line with the results of previous research, some nuances were identified. These results may inform educators, medical school curricula and education policy-makers.
... 7 More recently, a multicenter prospective study by the European Network for the Investigation of Gender Incongruence (ENIGI) examined the impact of hormone therapy on cardiovascular risk: after 2 years of GAHT, the risk of major cardiovascular accidents increased by 0.68% and was greater in the long term than in the cisgender women control group. 18 In another study, Nota et al. 76 had reported a > 3.5fold increase in the incidence of acute myocardial infarction in AFAB people after hormone therapy with respect to cisgender women, with no differences when compared with cisgender men. ...
... Previous work suggesting that GAHT in adults may have adverse effects on cardiometabolic health in Europe and the United States included individuals treated with ethinyl estradiol, not currently used in most GAHT regimens due to known adverse effects on cardiometabolic risk factors (511). Longitudinal studies using current hormone regimens are needed (512). ...
Endocrine care of pediatric and adult patients continues to be plagued by health and health care disparities that are perpetuated by the basic structures of our health systems and research modalities, as well as policies that impact access to care and social determinants of health. This scientific statement expands the Society's 2012 statement by focusing on endocrine disease disparities in the pediatric population and sexual and gender minority populations. These include pediatric and adult lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA) persons. The writing group focused on highly prevalent conditions-growth disorders, puberty, metabolic bone disease, type 1 (T1D) and type 2 (T2D) diabetes mellitus, prediabetes, and obesity. Several important findings emerged. Compared with females and non-White children, non-Hispanic White males are more likely to come to medical attention for short stature. Racially and ethnically diverse populations and males are underrepresented in studies of pubertal development and attainment of peak bone mass, with current norms based on European populations. Like adults, racial and ethnic minority youth suffer a higher burden of disease from obesity, T1D and T2D, and have less access to diabetes treatment technologies and bariatric surgery. LGBTQIA youth and adults also face discrimination and multiple barriers to endocrine care due to pathologizing sexual orientation and gender identity, lack of culturally competent care providers, and policies. Multilevel interventions to address these disparities are required. Inclusion of racial, ethnic, and LGBTQIA populations in longitudinal life course studies is needed to assess growth, puberty, and attainment of peak bone mass. Growth and development charts may need to be adapted to non-European populations. In addition, extension of these studies will be required to understand the clinical and physiologic consequences of interventions to address abnormal development in these populations. Health policies should be recrafted to remove barriers in care for children with obesity and/or diabetes and for LGBTQIA children and adults to facilitate comprehensive access to care, therapeutics, and technological advances. Public health interventions encompassing collection of accurate demographic and social needs data, including the intersection of social determinants of health with health outcomes, and enactment of population health level interventions will be essential tools.
... Medical risks are consequential: estrogen and testosterone for genderaffirming care degrade sexual organs, 41 which can also cause, e.g., significant pain from vaginal and uterine atrophy 42 and/or sexual dysfunction. Also observed are associated changes in the brain, [43][44][45][46] increases relative to birth sex of adverse cardiovascular events such as blood clots (venous thromboembolism; more than a factor of 4 for male to female), strokes (factors of more than 1.6 for both sexes) and heart attacks (more than a factor of 4 for female to male) 47,48 , as well as harmful changes to the endocrine system, 49 immune system (e.g., an increase in multiple sclerosis by a factor of 5 for male to female 50 ), and life span. 51,52 Surgeries are also of concern for adolescents, and include double mastectomies at ages as young as 13 53 and vaginoplasties for minors. ...
The 2022 article “Legislation restricting gender-affirming care for transgender youth: Politics eclipse healthcare” by K. L. Kraschel et al. implies that attempts in the United States to restrict medical interventions for gender dysphoria are due to political motivations. Although there are likely some whose stance on these interventions is based upon politics, there are sound medical reasons, independent of politics, for advocating for more cautious medical intervention protocols. Neglecting mention of these reasons obscures the fact that medical intervention outcomes are difficult to predict and that serious risks and irreversible consequences are present. In other countries, following extensive evidence review, supportive alternatives to medical intervention are being prioritized instead. Here, several claims of Kraschel et al. regarding the state of medical intervention healthcare are compared to the research evidence and shown to fall short. Healthcare issues alone justify challenging current United States medical treatment protocols.
... It is healthcare challenges related to medical gender transition. Gender-a rming medical procedures may be related to a range of side effect [25,26]. Medical transition (transitioning and gender-a rming medical procedures endocrine or surgical) is commonly accepted as effective treatment for gender dysphoria and associated with transgender individual's mental health [14]. ...
Aim: Transgender people face significantly greater health inequities than cisgender people and experience discrimination in health care settings. The role of education in eliminating this discrimination and health disparities has been increasingly recognized by many medical schools. However, transgender-health content lacks or is sparse and considerably varying across different medical curricula in many countries. In Greece, there is limited research on medical students’ attitudes towards transgender people. This study aims to contribute to filling this knowledge gap.
Method: The study adopted a cross-sectional, comparative-descriptive research design. Purposive non-probability sampling was used to recruit the study participants (N=203). The study was designed to validate the Transgender Attitudes and Beliefs Scale (TABS)-Greek version scale and examine medical students’ attitudes towards transgender people. The data was collected between December and February 2023.
Results: The overall reliability of the TABS questionnaire is high (Cronbach's α = 0.961, Sig. from Hotelling’s T-Squared Test < 0.000). High Cronbach’s alpha values were estimated on the three subscales with α = 0.958 for Interpersonal Comfort, α = 0.906 for Gender Beliefs, and α = 0.952 for Human Value. Hotelling’s T-Squared Test confirmed that all items on the scale have the same mean (Sig. < 0.001 for all subgroups). Confirmatory factor analysis (CFA) demonstrated adequate fit. Its convergent and discriminant validity was validated based on the estimated correlations. The three-factor structure of Greek TABS Version has been confirmed. The mean total score was 155.95 (SD. = 30.63) indicating that medical students had a moderately positive attitude towards transgender people. Participants showed significantly less biased (more tolerant, positive) attitudes towards transgender people on the Interpersonal Comfort (IC) and Human Value (HV) subscales than on the Sex/Gender Beliefs (SGB) subscale. Overall psychometric findings provide support for further use of the TABS-Gr in Greek medical schools. A demographic comparison was conducted and demonstrated correlation between scores and socio-demographics, except for sexual orientation and place of origin. A statistically significant increase in total mean score was estimated for females compared to males.
Conclusion: This study provide support for further use of the TABS in Greece and can contribute to providing the evidence required to persuade universities to make changes to their curriculum to ensure that future physicians are in the position to provide high quality health care for transgender patients.
... However, the current understanding of the burden of cardiovascular disease in TNB individuals is at times variable in the magnitude of estimates (16)(17)(18)(19). These variations in estimates may reflect studies that focus heavily on the use of gender-affirming hormone therapy (20)(21)(22)(23) without appropriately acknowledging highly relevant factors such as gender minority stress (16), lack of healthcare access (24), distrust of and discrimination within the healthcare system (25), greater socioeconomic burden (26,27), and health behaviors pertinent to cardiovascular disease (8). Given the variability in estimates and compounded by the lack of investments and prioritization from government and grant funding bodies due to structural transphobia, no evidence-based interventions for cardiovascular risk reduction specific to the TNB population currently exist. ...
Cardiovascular disease is the leading cause of morbidity and mortality globally. Transgender and non-binary (TNB) individuals face unclear but potentially significant cardiovascular health inequities, yet no TNB-specific evidence-based interventions for cardiovascular risk reduction currently exist. To address this gap, we propose a road map to improve the inclusion of TNB individuals in the planning, completion and mobilization of cardiovascular research. In doing so, the adoption of inclusive practices would optimize the cardiovascular health surveillance and care for TNB communities. Authors Statement: The authors of this manuscript represent diverse transdisciplinary and international and interdisciplinary expertise stemming from transgender, non-binary, and cisgender experiences. The authors each recognize their positionality and would like to highlight the inclusion and representation of TNB perspectives in this living document.
... This study controlled for BMI, blood pressure, smoking status, cholesterol level, and history of acute cardiovascular events, but not for other potential confounders (e.g., HIV status, concurrent antidepressant use, or psychosocial stressors). Similar risk differences were seen in a Dutch cohort of nearly 4,000 J o u r n a l P r e -p r o o f transgender women receiving GAHT 16 . In a representative sample of cisgender and transgender adults aged ≥40 years, there was no statistically significant association between hormone use and VTE (adjusted odds ratio [AOR] ...
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.
... with likely lower educational attainment (combined rates, 30.5% high school graduates; 13.3% never graduated from high-school) and likely to face challenges on employment (5.8% unemployed and 5.8% not able to work).110 A recent study evaluated the incidence of cardiovascular events in a large 90).111 A recent observational analysis of 114 transgender and 964 cisgender individuals 112 described a higher risk of VTE in male-tofemale transgenders compared to cis women (adjusted OR 3.94, 95% CI: 1.24-12.51), ...
Cardiovascular disease is the leading cause of death worldwide; however, women tend to be less affected than men during their reproductive years. The female cardiovascular risk increases significantly around the time of the menopausal transition. The loss of the protective action of ovarian oestrogens and the circulating androgens has been implicated in possibly inducing subclinical and overt changes in the cardiovascular system after the menopausal transition. In vitro studies performed in human or animal cell lines demonstrate an adverse effect of testosterone on endothelial cell function and nitric oxide bioavailability. Cohort studies evaluating associations between testosterone and/or dehydroepiandrosterone and subclinical vascular disease and clinical cardiovascular events show an increased risk for women with more pronounced androgenicity. However, a mediating effect of insulin resistance is possible. Data on cardiovascular implications following low-dose testosterone treatment in middle-aged women or high-dose testosterone supplementation for gender affirmatory purposes remain primarily inconsistent. It is prudent to consider the possible adverse association between testosterone and endothelial function during the decision-making process of the most appropriate treatment for a postmenopausal woman.
... 55 Similar to estrogen-containing therapies in cis women, the risk of VTE is increased with a history of thrombosis, thrombophilia, smoking, or obesity. 56 The available retrospective data demonstrate that the risk of VTE is highest with oral estrogen, particularly EE, and during the first year of therapy. Therefore, we recommend that individuals with the aforementioned high-risk features should be given formulations containing E 2 V or 17 -estradiol at the lowest possible dose. ...
Background:
Venous thromboses are well-established complications of hormonal therapy. Thrombosis risk is seen with both hormonal contraceptive agents and with hormone replacement therapy for menopause and gender transition. Over the past several decades, large epidemiological studies have helped better define these risks.
Objectives:
To review and discuss the differences in thrombosis risk of the many of hormonal preparations available as well as their interaction with patient-specific factors.
Methods:
We conducted a narrative review of the available literature regarding venous thrombosis and hormonal therapies including for contraception, menopausal symptoms, and gender transition.
Results:
Thrombosis risk with estrogen-containing compounds increases with increasing systemic dose of estrogen. While progesterone-only-containing products are not associated with thrombosis, when paired with estrogen in combined oral contraceptives, the formulation of progesterone does impact the risk. These components, along with patient-specific factors, may influence the choice of hormonal preparation. For patients who develop thrombosis on hormonal treatment, anticoagulation is protective against future thrombosis. Duration of anticoagulation is dependent on ongoing and future hormone therapy choice. Finally, the optimal management of hormone therapy for individuals diagnosed with prothrombotic illnesses such as COVID-19 remains unclear.
Conclusions:
When contemplating hormonal contraception or hormone replacement therapy, clinicians must consider a variety of factors including hormone type, dose, route, personal and family history of thrombosis, and other prothrombotic risk factors to make informed, personalized decisions regarding the risk of venous thrombosis.
... Particularly, the study from the Netherlands on 3875 transgender people reported a two-fold increase in myocardial infarction among transgender AFAB compared with ciswomen, but not cismen, a twofold increased risk for stroke and a five-fold increased risk for VTE for transgender AMAB compared with both cismen and ciswomen. 21 A more recent cohort study on 2509 transgender AMAB and 1893 transgender AFAB from the USA did not replicate the finding of increased risk of VTE with oestrogens treatment, whereas an increased risk was only found for a recent prescription of progestin. 22 A large cross-sectional study from the USA reported a higher reported history of myocardial infarction in transgender individuals under GAHT in comparison to the cisgender population, even after adjusting for cardiovascular risk factors. ...
Aims
We compared the incidence of cardiovascular disease (CVD) in transgender participants with a diagnosis of gender dysphoria (GD) with and without gender-affirming hormone therapy (GAHT) to the incidence observed in the general population.
Methods and Results
The population-based cohort included all individuals >10 years in Sweden linked to Swedish nationwide healthcare Registers (2006-2016). Two comparator groups without GD/GAHT were matched (1:10) on age, county of residence, and on male and female birth-assigned sex, respectively. Cox proportional models provided hazard ratios (HR) and 95% confidence intervals (CI) for CVD outcomes. Among 1779 transgender individuals (48% birth-assigned males [AMAB], 52% birth-assigned females [AFAB]) 18 developed CVD, most of which were conduction disorders. The incidence of CVD for AFAB individuals with GD was 3.7 per 1000 person-years (95%CI: 1.4-10.0). AMAB individuals with GD had an incidence of CVD event of 7.1 per 1000 person-years (95%CI: 4.2-12.0). The risk of CVD event was 2.4 times higher in AMAB individuals (HR: 2.4, 95%CI: 1.3-4.2) compared to cisgender women, and 1.7 higher compared to cisgender men (HR: 1.7, 95%CI: 1.0-2.9). Analysis limited to transgender individuals without GAHT yielded similar results to those with GAHT treatment.
Conclusion
The incidence of CVD among GD/GAHT individuals was low, although increased compared to matched individuals without GD and similar to the incidence among GD/no GAHT individuals, thus not lending support for a causal relationship between treatment and CVD outcomes. Larger studies with longer follow-up are needed to verify these findings, as well as possible effect modification by comorbidity.
... Data are not sufficient to associate testosterone therapy with polycythemia itself, and no increase in rates of VTE has been reported in transgender people receiving exogenous testosterone. 91,94,[107][108][109] Also, data are not sufficient to stratify the hematocrit increase by route of testosterone administration or by testosterone formulation. However, data in cisgender men suggest that exogenous testosterone may increase the risk of thromboembolism, although data are overall mixed and likely inadequate. ...
Sexual and gender minority (SGM) people, including agender, asexual, bisexual, gay, gender diverse, genderqueer, genderfluid, intersex, lesbian, nonbinary, pansexual, queer, and transgender people, comprise approximately 10% or more of the U.S. population. Thus, most oncologists see SGM patients whether they know it or not. SGM people experience stigma and structural discrimination that lead to cancer disparities. Because of the lack of systematic and comprehensive data collection, data regarding SGM cancer incidence, outcomes, and treatment responses are limited. Collection of data regarding sexual orientation, gender identity, transgender identity and/or experience, anatomy, and serum hormone concentrations in oncology settings would drastically increase collective knowledge about the impact of stigma and biologic markers on cancer outcomes. Increasing the safety of oncology settings for SGM people will require individual, institutional, and systems changes that will likely improve oncologic care for all patients.
Gender-affirming hormone treatment (GAHT) is one of the main demands of transgender and gender diverse (TGD) people, who are usually categorised as transgender assigned-male-at birth (AMAB) and assigned-female-at birth (AFAB). The aim of the study is to investigate the long-term therapeutic management of GAHT, considering hormonal targets, treatment adjustments and GAHT safety.
A retrospective, longitudinal, observational, multicentre clinical study was carried out. Transgender people, both AMAB and AFAB, were recruited from two Endocrinology Units in Italy (Turin and Modena) between 2005 and 2022. Each subject was managed with specific and personalized follow-up depending on the clinical practice of the Centre. All clinical data routinely collected were extracted, including anthropometric and biochemical parameters, lifestyle habits, GAHT regime, and cardiovascular events.
Three-hundred and two transgender AFAB and 453 transgender AMAB were included. Similar follow-up duration (p = 0.974) and visits’ number (p = 0.384) were detected between groups. The transgender AFAB group reached therapeutic goals in less time (p = 0.002), fewer visits (p = 0.006) and fewer adjustments of GAHT scheme (p = 0.024). Accordingly, transgender AFAB showed a higher adherence to medical prescriptions compared to transgender AMAB people (p < 0.001). No significantly increased rate of cardiovascular events was detected in both groups.
Our real-world clinical study shows that transgender AFAB achieve hormone target earlier and more frequently in comparison to transgender AMAB individuals. Therefore, transgender AMAB people may require more frequent check-ups in order to tailor feminizing GAHT and increase therapeutic adherence.
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Testosterone and cardiovascular health: Questions and controversies. DVT, deep vein thrombosis; FDA, Food and Drug Administration; T, testosterone; TGM, transgender men; TT, testosterone therapy; VTE, venous thromboembolism.
As more individuals seek to align their physical characteristics with their gender identity, transgender health care is a growing medical field which is no longer the remit of a few selected clinicians. Gender‐affirming hormone therapy (GAHT) is a mainstay treatment in gender reassignment and its medium‐ to long‐term metabolic sequelae are gradually emerging. Although hampered by the scarcity of prospective controlled studies involving large diverse cohorts, evidence suggests a potential adverse impact for at least some cardiovascular disease (CVD) risk factors. If left unmanaged, this could manifest in a higher CVD events rate for this treatment group. Increased vigilance and awareness among health care professionals about the consequential risks of GAHT are important for proactive mitigation of this. Copyright © 2023 John Wiley & Sons.
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.
Introduction:
There has been a drastic increase in the reported number of people seeking help for gender dysphoria in many countries over the last two decades. Yet, our knowledge of gender dysphoria and related outcomes is restricted due to the lack of high-quality studies employing comprehensive approaches. This longitudinal study aims to enhance our knowledge of gender dysphoria; different aspects will be scrutinised, focusing primarily on the psychosocial and mental health outcomes, prognostic markers and, secondarily, on the underlying mechanisms for its origin.
Methods and analysis:
The Swedish Gender Dysphoria Study is an ongoing multicentre longitudinal cohort study with 501 registered participants with gender dysphoria who are 15 years old or older. Participants at different phases of their clinical evaluation process can enter the study, and the expected follow-up duration is three years. The study also includes a comparison group of 458 age- and county-matched individuals without gender dysphoria. Data on the core outcomes of the study, which are gender incongruence and experienced gender dysphoria, body satisfaction and satisfaction with gender-affirming treatments, as well as other relevant outcomes, including mental health, social functioning and life satisfaction, are collected via web surveys. Two different research visits, before and after starting on gender-affirming hormonal treatment (if applicable), are planned to collect respective biological and cognitive measures. Data analysis will be performed using appropriate biostatistical methods. A power analysis showed that the current sample size is big enough to analyse continuous and categorical outcomes, and participant recruitment will continue until December 2022.
Ethics and dissemination:
The ethical permission for this study was obtained from the Local Ethical Review Board in Uppsala, Sweden. Results of the study will be presented at national and international conferences and published in peer-reviewed journals. Dissemination will also be implemented through the Swedish Gender Dysphoria Study network in Sweden.
Gender affirming hormone therapy (GAHT) is used by many transgender people to reduce gender incongruence and improve psychological functioning. As GAHT shares many similarities with menopausal hormone therapy, clinicians supporting people through menopause are ideally placed to manage GAHT. This narrative review provides an overview of transgender health and discusses long-term effects of GAHT to consider when managing transgender individuals across the lifespan. Menopause is less relevant for transgender individuals who take GAHT (often given lifelong) to achieve sex steroid concentrations generally in the range of the affirmed gender. For people using feminizing hormone therapy, there is an elevated risk of venous thromboembolism, myocardial infarction, stroke and osteoporosis relative to cisgender individuals. For trans people using masculinizing hormone therapy, there is an increased risk of polycythemia, probable higher risk of myocardial infarction and pelvic pain which is poorly understood. Proactive mitigation of cardiovascular risk factors is important for all transgender people and optimization of bone health is important for those using feminizing hormones. With a lack of research to guide GAHT in older age, a shared decision-making approach is recommended for the provision of GAHT to achieve individual goals whilst minimizing potential adverse effects.
Transgender and gender-diverse (TGD) people endure numerous physical and mental health disparities secondary to lifelong stigma and marginalization, which are often perpetuated in medical spaces. Despite such barriers, TGD people are seeking gender-affirming care (GAC) with increased frequency. GAC facilitates the transition from the sex assigned at birth to the affirmed gender identity and is comprised of hormone therapy (HT) and gender-affirming surgery (GAS). The anesthesia professional is uniquely poised to serve as an integral support for TGD patients within the perioperative space. To provide affirmative perioperative care to TGD patients, anesthesia professionals should understand and attend to the biological, psychological, and social dimensions of health that are relevant to this population. This review outlines the biological factors that impact the perioperative care of TGD patients, such as the management of estrogen and testosterone HT, safe use of sugammadex, interpretation of laboratory values in the context of HT, pregnancy testing, drug dosing, breast binding, altered airway and urethral anatomy after prior GAS, pain management, and other GAS considerations. Psychosocial factors are reviewed, including mental health disparities, health care provider mistrust, effective patient communication, and the interplay of these factors in the postanesthesia care unit. Finally, recommendations to improve TGD perioperative care are reviewed through an organizational approach with an emphasis on TGD-focused medical education. These factors are discussed through the lens of patient affirmation and advocacy with the intent to educate the anesthesia professional on the perioperative management of TGD patients.
Context
The effects of androgen therapy on arterial function in transgender men (TM) are not fully understood, particularly concerning long-term androgen treatment.
Objective
To evaluate arterial stiffness in TM receiving long-term gender-affirming hormone therapy by carotid–femoral pulse wave velocity (cf-PWV).
Methods
A cross-sectional case–control study at the Gender Dysphoria Unit of the Division of Endocrinology, HC-FMUSP, Sao Paulo, Brazil. Thirty-three TM receiving intramuscular testosterone esters as regular treatment for an average time of 14 ± 8 years were compared with 111 healthy cisgender men and women controls matched for age and body mass index. Aortic stiffness was evaluated by cf-PWV measurements using Complior device post-testosterone therapy. The main outcome measure was aortic stiffness by cf-PWV as a cardiovascular risk marker in TM and control group.
Results
The cf-PWV after long-term testosterone therapy was significantly higher in TM (7.4 ± 0.9 m/s; range 5.8-8.9 m/s) than in cisgender men (6.6 ± 1.0 m/s; range 3.8-9.0 m/s, P < .01) and cisgender women controls (6.9 ± .9 m/s; range 4.8-9.1 m/s, P = .02). The cf-PWV was significantly and positively correlated with age. Analysis using blood pressure as a covariate showed a significant relationship between TM systolic blood pressure (SBP) and cf-PWV in relation to cisgender women but not to cisgender men. Age, SBP, and diagnosis of hypertension were independently associated with cf-PWV in the TM group.
Conclusion
The TM group on long-term treatment with testosterone had higher aging-related aortic stiffening than the control groups. These findings indicate that aortic stiffness might be accelerated in the TM group receiving gender-affirming hormone treatment, and suggest a potential deleterious effect of testosterone on arterial function. Preventive measures in TM individuals receiving testosterone treatment, who are at higher risk for cardiovascular events, are highly recommended.
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.
Transgender and nonbinary (TGNB) patients who desire gender-affirming therapy are often treated with hormones to help align their external appearance with their gender identity. This practice is generally safe, and studies have shown that gender-affirming therapy has positive physical and psychological effects for many TGNB individuals. Masculinizing hormone therapy involves administration of exogenous testosterone. Expected changes include cessation of menses, deepening of the voice, and development of terminal facial and body hair. Testosterone therapy increases the risk of polycythemia. Feminizing hormone therapy typically involves the use of estrogen and an anti-androgen, and can produce physical changes such as breast growth, changes in fat distribution, and redistribution of hair growth. Transfeminine individuals may have an increased risk of breast cancer and thromboembolism based on recent cohort studies, although this has yet to be confirmed with randomized controlled trials. Regular surveillance is essential to establish the proper hormone dosage and detect complications. Important long-term considerations include metabolic, cardiovascular, and skeletal health. Gender-affirming surgeries are also available and may improve outcomes in some patients. Gender dysphoric adolescents entering puberty can opt for reversible pubertal suppression, which may make future gender-affirming treatment easier to accomplish. High-quality, long-term studies on the effectiveness and safety of gender-affirming treatments in both adults and adolescents are lacking, but the current evidence suggests that they are overall safe and effective with appropriate oversight.
Importance
Limited prior research suggests that transgender and gender diverse (TGD) people may have higher mortality rates than cisgender people.
Objective
To estimate overall and cause-specific mortality among TGD persons compared with cisgender persons.
Design, Setting, and Participants
This population-based cohort study used data from general practices in England contributing to the UK’s Clinical Practice Research Datalink GOLD and Aurum databases. Transfeminine (assigned male at birth) and transmasculine (assigned female at birth) individuals were identified using diagnosis codes for gender incongruence, between 1988 and 2019, and were matched to cisgender men and women according to birth year, practice, and practice registration date and linked to the Office of National Statistics death registration. Data analysis was performed from February to June 2022.
Main Outcomes and Measures
Cause-specific mortality counts were calculated for categories of disease as defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision chapters. Overall and cause-specific mortality rate ratios (MRRs) were estimated using Poisson models, adjusted for index age, index year, race and ethnicity, Index of Multiple Deprivation, smoking status, alcohol use, and body mass index.
Results
A total of 1951 transfeminine (mean [SE] age, 36.90 [0.34] years; 1801 White [92.3%]) and 1364 transmasculine (mean [SE] age, 29.20 [0.36] years; 1235 White [90.4%]) individuals were matched with 68 165 cisgender men (mean [SE] age, 33.60 [0.05] years; 59 136 White [86.8%]) and 68 004 cisgender women (mean [SE] age, 33.50 [0.05] years; 57 762 White [84.9%]). The mortality rate was 528.11 deaths per 100 000 person-years (102 deaths) for transfeminine persons, 325.86 deaths per 100 000 person-years (34 deaths) for transmasculine persons, 315.32 deaths per 100 000 person-years (1951 deaths) for cisgender men, and 260.61 deaths per 100 000 person-years (1608 deaths) for cisgender women. Transfeminine persons had a higher overall mortality risk compared with cisgender men (MRR, 1.34; 95% CI, 1.06-1.68) and cisgender women (MRR, 1.60; 95% CI, 1.27-2.01). For transmasculine persons, the overall MMR was 1.43 (95% CI, 0.87-2.33) compared with cisgender men and was 1.75 (95% CI, 1.08-2.83) compared with cisgender women. Transfeminine individuals had lower cancer mortality than cisgender women (MRR, 0.52; 95% CI, 0.32-0.83) but an increased risk of external causes of death (MRR, 1.92; 95% CI, 1.05-3.50). Transmasculine persons had higher mortality from external causes of death than cisgender women (MRR, 2.77; 95% CI, 1.15-6.65). Compared with cisgender men, neither transfeminine nor transmasculine adults had a significantly increased risk of deaths due to external causes.
Conclusions and Relevance
In this cohort study of primary care data, TGD persons had elevated mortality rates compared with cisgender persons, particularly for deaths due to external causes. Further research is needed to examine how minority stress may be contributing to deaths among TGD individuals to reduce mortality.
There is significant disagreement about how to support trans-identified or gender-dysphoric young people. Different experts and expert bodies make strikingly different recommendations based upon the same (limited) evidence. The US-originating "gender-affirmative" model emphasizes social transition and medical intervention, while some other countries, in response to evidence reviews of medical intervention outcomes, have adopted psychological interventions as the first line of treatment. A proposed model of gender-affirming care, comprising only medical intervention for "eligible" youth, is described in Rosenthal (2021). Determining eligibility for these medical interventions is challenging and engenders considerable disagreement among experts, neither of which is mentioned. The review also claims without support that medical interventions have been shown to clearly benefit mental health, and leaves out significant risks and less invasive alternatives. The unreliability of outcome studies and the corresponding uncertainties as to how gender dysphoria develops and responds to treatment are also unreported.
Aujourd’hui encore, la prise en charge médicale des personnes transgenres pâtit d’une insuffisance d’offre de soins et de formation des soignants. La mise en œuvre d’une hormonothérapie est souvent souhaitée par les personnes transgenres et il est nécessaire qu’un médecin sache l’instaurer et la suivre tout au long de la transition. Nous abordons dans cette revue le traitement hormonal féminisant (THF) chez les femmes transgenres adultes, et le traitement hormonal masculinisant (THM) chez les hommes transgenres adultes.
Recent years have seen an increase in the number of people openly identifying as transgender in the UK, with current estimates ranging between 200 000 and 600 000 individuals. There has also been an increase in the number of patients undergoing both medical and surgical gender-affirming treatment. There are several important, specific considerations that perioperative clinicians must be aware of when caring for transgender patients, including changes to the airway, potential respiratory and cardiovascular complications, and the management of hormone therapy. Alongside this, important general considerations include the correct use of patient pronouns and ensuring patients are admitted to correctly gendered wards. Despite the need for these considerations, the perioperative management of transgender patients is not covered in the Royal College of Anaesthetists' curriculum; to date, no national guidelines exist on the subject. This article discusses some of the key, specific perioperative considerations relevant to transgender patients, and highlights the need for national guidelines and improved education on the subject.
Background: Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8.
Aim: The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment.
Methods: The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings.
Results: A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health.
Conclusions: The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person.
Context
Studies on cardiometabolic health in transgender and gender diverse youth (TGDY) are limited to small cohorts.
Objective
To determine the odds of cardiometabolic-related diagnoses in TGDY compared to matched controls in a cross-sectional analysis, using a large, multisite database (PEDSnet).
Design
Electronic health record data (2009-2019) were used to determine odds of cardiometabolic-related outcomes based on diagnosis, anthropometric and laboratory data using logistic regression among TGDY youth vs. controls. The association of gender affirming hormone therapy (GAHT) with these outcomes was examined separately among TGDY.
Setting
Six PEDSnet sites.
Patients or Other Participants
TGDY (n=4,172) were extracted from PEDSnet and propensity-score matched on 8 variables to controls (n=16,648).
Intervention(s)
N/A.
Main Outcome Measure(s)
Odds of having cardiometabolic-related diagnoses among TGDY compared to matched controls, and among TGDY prescribed GAHT compared to those not prescribed GAHT.
Results
In adjusted analyses, TGDY had higher odds of overweight/obesity (1.2 [95% confidence interval 1.1-1.3]) than controls. TGDY with a testosterone prescription alone or in combination with a gonadotropin releasing hormone agonist (GnRHa) had higher odds of dyslipidemia (1.7 [1.3-2.3], 3.7 [2.1-6.7], respectively) and liver dysfunction (1.5 [1.1-1.9], 2.5 [1.4-4.3]) than TGDY not prescribed GAHT. TGDY with a testosterone prescription alone had higher odds of overweight/obesity (1.8 [1.5-2.1]) and hypertension (1.6 [1.2-2.2]) than those not prescribed testosterone. Estradiol and GnRHa alone were not associated with greater odds of cardiometabolic-related diagnoses.
Conclusions
TGDY have increased odds of overweight/obesity compared to matched controls. Screening and tailored weight management, sensitive to the needs of TGDY, are needed.
Women diagnosed with heart failure report worse quality of life than men on patient-reported outcome (PRO) measures. An inherent assumption of PRO measures in heart failure is that women and men interpret questions about quality of life the same way. If this is not the case, the risk then becomes that the PRO scores cannot validly be used to compare or to combine outcomes by subgroups of the population. Inability to validly compare subgroups is a broad issue with implications for clinical trials, and it also has specific and important implications for identifying and beginning to address health inequities. We describe this threat to validity (the psychometric term is differential item functioning), why it is so important in heart failure outcomes, what research has been conducted thus far in this area, what gaps remain, and what we can do to avoid this threat to validity. PROs bring unique information to clinical decision-making, and the validity of PRO measures is key to interpreting differences in heart failure outcomes.
Background: Although there are sex differences in metabolomic profiles, little is known about the effects of testosterone on the metabolomic profile of people with a female sex. We evaluated the effect of endogenous versus exogenous testosterone on the plasma metabolomic profile.
Methods: Participants included 20 individuals with a female sex designated at birth. Ten transgender male (TGM) adolescents [age 15.5 + 0.9 years, BMI percentile 74% (32, 94)] were evaluated at baseline and after one month of exogenous testosterone treatment (TGM-1M). TGM-1M were compared to 10 BMI-matched cisgender female adolescents with polycystic ovary syndrome [PCOS, age 15.8 + 1.8 years, BMI 85% (78, 98)]. All participants had fasting laboratory evaluation and targeted fasting plasma metabolomic analysis.
Results: There were no significant differences in metabolomics after 1 month of testosterone therapy in the TGM group. There were significant differences in the targeted metabolomic analysis between the adolescents with PCOS and TGM-1M. Eight bile acids, 5 fatty acids and 2 amino acids were higher in the PCOS group (fold change>2) compared to TGM-1M. Five amino acids, 2 acylcarnitines, and one fatty acid were higher in TGM-1M compared to participants with PCOS. Participants with PCOS had more signs of metabolic syndrome, including higher waist/hip ratio, systolic blood pressure, and dyslipidemia compared to TGM-1M.
Conclusions: Long-term endogenous testosterone exposure in PCOS is associated with an altered metabolic profile and changes in bile acid and fatty acid metabolism relative to short-term exogenous exposure in TGM-1M, suggesting other features, besides testosterone are responsible for the metabolic features of PCOS.
Objective:
Limited data are available on adverse drug reactions (ADRs) of gender-affirming hormone therapy (HT), mainly due to the lack of population-based studies with adequate controls, thus making spontaneous reporting systems a valuable tool to detect potential side reactions. In this nationwide retrospective study, we aimed to analyze ADRs related to gender-affirming HT reported in the French pharmacovigilance database (FPVD).
Design:
We requested all the individual case safety reports related to gender-affirming HT recorded in the FPVD before May 27, 2020. We excluded previously published cases and those where gender-affirming HT was not the suspected drug.
Results:
A total of 28 reports of ADRs were identified. Six concerned transgender men (21-40 years) and 22 transgender women (22-68 years). In transgender men taking testosterone enanthate, all reported ADRs were cardiovascular events, with pulmonary embolism in 50% of cases. Median time to onset (TTO) was 34 months. In transgender women, antiandrogens, mainly cyproterone acetate, were involved in 68% of cases, and estrogens in 77% of cases, mostly in association with progestin or cyproterone acetate. Meningiomas were the principal ADRs, followed by cardiovascular events, with a median TTO of 5.3 months.
Conclusions:
Our data show a previously unreported, non-negligible proportion of cases indicating cardiovascular ADRs in transgender men younger than 40 years. In transgender women, cardiovascular events were the second most frequent ADR. Further research is necessary to identify risk factors that might help to the individualization of treatment strategies. There is a necessity to increase awareness, implement preventive and education measures.
Transgender and gender diverse (TGD) individuals may undergo a wide range of care during gender transition including mental health counseling, gender-affirming hormonal therapy, and various surgeries. Hormone therapy effectively converts the hormonal milieu into that of the affirmed gender and produces measurable alterations in serum markers for coronary artery disease and other hematologic conditions (eg, erythrocytosis, venous thrombosis). Although illegal in the United States, some transgender women may receive silicone injections for breast and soft tissue augmentation, which can lead to devastating local complications, as well as silicone migration, pulmonary embolism, systemic reactions, and death. Smoking rates are higher among transgender and sexual minority populations, placing them at elevated risk of smoking-related diseases, including lung cancer. Some opportunistic infections may be more common in the TGD populations, attributable to higher rates of coexisting infection with human immunodeficiency virus. Radiologists should be aware that these patients may develop cancer of their natal organs (eg, breast, prostate), especially as some of these tissues are not completely removed during gender-affirming surgery, which may manifest with thoracic involvement by secondary neoplasia. As more TGD patients seek medical care, thoracic radiologists can reasonably expect to interpret imaging performed in this population and should be aware of possible disease processes and potential complications of hormonal and surgical therapies.
The incidence of venous thromboembolism has not been well described, and there are no studies of long-term trends in the incidence of venous thromboembolism.
To estimate the incidence of deep vein thrombosis and pulmonary embolism and to describe trends in incidence.
We performed a retrospective review of the complete medical records from a population-based inception cohort of 2218 patients who resided within Olmsted County, Minnesota, and had an incident deep vein thrombosis or pulmonary embolism during the 25-year period from 1966 through 1990.
The overall average age- and sex-adjusted annual incidence of venous thromboembolism was 117 per 100000 (deep vein thrombosis, 48 per 100000; pulmonary embolism, 69 per 100000), with higher age-adjusted rates among males than females (130 vs 110 per 100000, respectively). The incidence of venous thromboembolism rose markedly with increasing age for both sexes, with pulmonary embolism accounting for most of the increase. The incidence of pulmonary embolism was approximately 45% lower during the last 15 years of the study for both sexes and all age strata, while the incidence of deep vein thrombosis remained constant for males across all age strata, decreased for females younger than 55 years, and increased for women older than 60 years.
Venous thromboembolism is a major national health problem, especially among the elderly. While the incidence of pulmonary embolism has decreased over time, the incidence of deep vein thrombosis remains unchanged for men and is increasing for older women. These findings emphasize the need for more accurate identification of patients at risk for venous thromboembolism, as well as a safe and effective prophylaxis.
Background:
Venous thromboembolism (VTE), ischemic stroke, and myocardial infarction in transgender persons may be related to hormone use.
Objective:
To examine the incidence of these events in a cohort of transgender persons.
Design:
Electronic medical record-based cohort study of transgender members of integrated health care systems who had an index date (first evidence of transgender status) from 2006 through 2014. Ten male and 10 female cisgender enrollees were matched to each transgender participant by year of birth, race/ethnicity, study site, and index date enrollment.
Setting:
Kaiser Permanente in Georgia and northern and southern California.
Patients:
2842 transfeminine and 2118 transmasculine members with a mean follow-up of 4.0 and 3.6 years, respectively, matched to 48 686 cisgender men and 48 775 cisgender women.
Measurements:
VTE, ischemic stroke, and myocardial infarction events ascertained from diagnostic codes through the end of 2016 in transgender and reference cohorts.
Results:
Transfeminine participants had a higher incidence of VTE, with 2- and 8-year risk differences of 4.1 (95% CI, 1.6 to 6.7) and 16.7 (CI, 6.4 to 27.5) per 1000 persons relative to cisgender men and 3.4 (CI, 1.1 to 5.6) and 13.7 (CI, 4.1 to 22.7) relative to cisgender women. The overall analyses for ischemic stroke and myocardial infarction demonstrated similar incidence across groups. More pronounced differences for VTE and ischemic stroke were observed among transfeminine participants who initiated hormone therapy during follow-up. The evidence was insufficient to allow conclusions regarding risk among transmasculine participants.
Limitation:
Inability to determine which transgender members received hormones elsewhere.
Conclusion:
The patterns of increases in VTE and ischemic stroke rates among transfeminine persons are not consistent with those observed in cisgender women. These results may indicate the need for long-term vigilance in identifying vascular side effects of cross-sex estrogen.
Primary funding source:
Patient-Centered Outcomes Research Institute and Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Recent reports estimate that 0.6% of adults in the United States, or approximately 1.4 million persons, identify as transgender. Despite gains in rights and media attention, the reality is that transgender persons experience health disparities, and a dearth of research and evidence-based guidelines remains regarding their specific health needs. The lack of research to characterize cardiovascular disease (CVD) and CVD risk factors in transgender populations receiving cross-sex hormone therapy (CSHT) limits appropriate primary and specialty care. As with hormone therapy in cisgender persons (that is, those whose sex assigned at birth aligns with their gender identity), existing research in transgender populations suggests that CVD risk factors are altered by CSHT. Currently, systemic hormone replacement for cisgender adults requires a nuanced discussion based on baseline risk factors and age of administration of exogenous hormones because of concern regarding an increased risk for myocardial infarction and stroke. For transgender adults, CSHT has been associated with the potential for worsening CVD risk factors (such as blood pressure elevation, insulin resistance, and lipid derangements), although these changes have not been associated with increases in morbidity or mortality in transgender men receiving CSHT. For transgender women, CSHT has known thromboembolic risk, and lower-dose transdermal estrogen formulations are preferred over high-dose oral formulations. In addition, many studies of transgender adults focus predominantly on younger persons, limiting the generalizability of CSHT in older transgender adults. The lack of randomized controlled trials comparing various routes and formulations of CSHT, as well as the paucity of prospective cohort studies, limits knowledge of any associations between CSHT and CVD.
Information on incidence of stroke is important for developing and maintaining public health strategies in primary and secondary prevention. Nationwide data on the incidence of stroke are scarce and absent for the Netherlands.
New cases of first stroke and stroke subtypes in the Dutch population in 2000 were identified through linkage of national registers and included hospitalized patients for first stroke and out-of-hospital deaths from first stroke. The number of non-fatal, non-hospitalized stroke patients was estimated based on data from the Rotterdam study, a population based cohort.
We identified 26,556 patients with a first stroke (20,798 hospitalized patients, 5758 out-of-hospital deaths). The number of non-fatal, non-hospitalized first stroke patients was estimated to be 12,255. Extrapolation of the data to the total Dutch population led to an overall estimate of approximately 41,000 patients with a first stroke. Stroke incidence increased with age and was higher in men than in women, except in the lowest (< 45 years) and highest age group (> 85 years).
The present study provides for the first time incidence estimates of first stroke (hospitalized patients, out-of hospital deaths and non-fatal, non-hospitalized patients) based upon virtually the entire Dutch population.
To study the incidence of first acute myocardial infarction (AMi) in the Netherlands. Background: We recently showed that AMi patients can be followed longitudinally within dutch national medical registrations in a valid way. This makes it possible to provide nationwide incidence estimates of first AMi in the Netherlands.
New cases of first AMi in the dutch population in 2000 were identified through linkage of the national hospital discharge register, the population register and the cause of death statistics and included hospitalised first Ami patients and out-of-hospital deaths from first AMi. Results: 31,777 patients with a first AMi were identified. The incidence (per 100,000 persons per year) increased from 2 in men aged <30 years to 2996 in men aged > or = 90 years. Corresponding figures for women ranged from 1 to 2226. The incidence was higher in men than in women in all age groups, but the male-to-female ratio decreased after the age of 50-59 year. Of all first AMI patients, 40% died before being admitted to a hospital. The proportion of non-hospitalised AMI patients increased with age in men after the age of 50-59 years. Within the age groups the proportion of out-of-hospital deaths was similar for men and women.
Our study provides the first nationwide incidence estimates of first AMI in the Netherlands. Expected differences in incidence with regard to age and gender were shown. The large proportion of out-of-hospital deaths reinforces the importance of primary prevention AMI.
Incidence of Deep Vein Thrombosis and Pulmonary Embolism
Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study
- M D Silverstein
- J A Heit
- D N Mohr
- T M Petterson
- W M O'fallon
- L J Melton
- Iii
Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ III.
Trends in the incidence of deep vein thrombosis and pulmonary embolism:
a 25-year population-based study. Arch Intern Med. 1998;158:585-593.
Standardized Incidence Ratios for Acute Cardiovascular Events in Transwomen and Transmen Receiving Hormone Therapy Acute Cardiovascular Events OCs
- Table
Table. Standardized Incidence Ratios for Acute Cardiovascular Events in Transwomen and Transmen Receiving Hormone Therapy
Acute Cardiovascular Events
OCs (IR)*
Cross-sex hormones and acute cardiovascular events in transgender persons: a cohort study
- D Getahun
- R Nash
- W D Flanders
- T C Baird
- T A Becerra-Culqui
- L Cromwell
- E Hunkeler
- T L Lash
- A Millman
- V P Quinn
- B Robinson
- D Roblin
- M J Silverberg
- J Safer
- J Slovis
- V Tangpricha
- M Goodman
Getahun D, Nash R, Flanders WD, Baird TC, Becerra-Culqui TA, Cromwell
L, Hunkeler E, Lash TL, Millman A, Quinn VP, Robinson B, Roblin D, Silverberg MJ, Safer J, Slovis J, Tangpricha V, Goodman M. Cross-sex hormones
and acute cardiovascular events in transgender persons: a cohort study.
Ann Intern Med. 2018;169:205-213. doi: 10.7326/M17-2785