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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.
... Whether these traits translate into the transgender population is still incompletely understood. So far, available data indicate that transgender women display an increased myocardial infarction risk compared with cisgender women; however, not compared with cisgender men (11)(12)(13). Transgender men appear to also have an increased cardiovascular disease risk, which in one study was discernible only in comparison to cisgender women (11), while in another it extended to the comparison with cisgender men (13). Most of this work is confounded by using self-reports, lack of information with respect to genderaffirming hormone therapy, and inclusion of transgender women taking ethinyl estradiol, which has strong adverse cardiometabolic effects and is therefore currently no longer in use (12,13). ...
... So far, available data indicate that transgender women display an increased myocardial infarction risk compared with cisgender women; however, not compared with cisgender men (11)(12)(13). Transgender men appear to also have an increased cardiovascular disease risk, which in one study was discernible only in comparison to cisgender women (11), while in another it extended to the comparison with cisgender men (13). Most of this work is confounded by using self-reports, lack of information with respect to genderaffirming hormone therapy, and inclusion of transgender women taking ethinyl estradiol, which has strong adverse cardiometabolic effects and is therefore currently no longer in use (12,13). ...
... Although gender-affirming hormonal treatment is increasingly prevalent, there is only weak evidence available in the group of transgender individuals with respect to long-term clinical outcomes, specifically regarding cardiometabolic disease (11)(12)(13). Longitudinal studies are scarce, and the effect of sex hormones vs sex chromosomes is incompletely understood. This mean that changes in biomarkers and the dynamic adjustment of risk profiles in response to the different hormonal interventions over time within a transgender individual are not fully known. ...
Background
While transgender individuals represent a significant group seeking medical care, the differential effect of sex on cardiometabolic risk metrics is incompletely understood. Therefore, the current study aimed to characterize the impact of sex hormones and chromosomes on a contemporary panel of cardiometabolic risk biomarkers and functional cardiovascular measurements.
Methods
17 transmen and 17 transwomen were studied at baseline (T0), 4 weeks (hormonal castration, T1), and 11 months following gender-affirming hormone treatment (T12). We analyzed carotid intima-media thickness (cIMT) and arterial stiffness, lipoproteins and other metabolites comprehensively by nuclear magnetic resonance spectroscopy and HDL-mediated cholesterol efflux capacity (CEC) from macrophages. T0 to T12 comparisons informed the impact of sex hormones, comparisons of genetic XX and XY individuals at T1 the impact of sex chromosomes.
Results
Vascular function was comparable at T12 and T0; systolic blood pressure increased in transmen (p=0.002). Transmen developed a pro-atherogenic lipoprotein profile, estrogen treatment in transwomen tended to result in improvements. Several metabolites indicating increased diabetes risk including plasma glucose were changed in transmen (p=0.025), with opposite changes in transwomen (p=0.002). Interestingly, at T1 apparent diabetes risk was lower in XX compared with XY individuals (p=0.002). CEC decreased in transwomen (p<0.01), while remaining unchanged in transmen. However, in both groups the strong positive association of apoA-I with cholesterol efflux observed at T0 was lost at T12.
Conclusions
The results are consistent with increased cardiometabolic risk in transmen, while transwomen show beneficial changes early during gender-affirming hormone therapy. Sex chromosomes have less intrinsic effects. XY individuals and transmen display an increased apparent diabetes risk. Further research of cardiometabolic risk is needed for transgender individuals.
... One large study of 2517 transgender women found a standardised incidence ratio of VTE of 5.52 comparing transgender women receiving GAHT to cisgender women. 41 Notably, when the authors performed subanalyses to exclude transgender women who started GAHT before 2001, at which time ethinyl estradiol was replaced by more natural oestrogens, the standardised incidence ratio (SIR) decreased from 5.52 to 3.92. Another large study of 2842 transgender women found that transgender women overall had a higher incidence of VTE than cisgender women and cisgender men, and that the risk of VTE further increased in transgender women taking GAHT. ...
... Similarly, a study of 1358 transgender men found a non-significant difference in the age-adjusted standardised incidence ratio of VTE in transgender men on GAHT compared with cisgender men. 41 These findings are further supported by Poteat et al, who found no significant difference in VTE between transgender men and cisgender men or cisgender women. 43 ...
... Prior studies have found a significantly higher incidence of transient ischaemic attack 51 and stroke 41 42 in transgender women on GAHT compared with cisgender women and an equivalent stroke risk when compared with cisgender men. 41 Nota et al also show an increased risk of myocardial infarction (MI) in transgender women compared with cisgender women. Importantly, this study did not control for smoking, especially relevant given the high prevalence of tobacco product use in the transgender community. ...
Orthopaedic and sports medicine clinicians can improve outcomes for transgender patients by understanding the physiological effects of gender-affirming hormone therapy (GAHT). This narrative review investigated the role of GAHT on bone mineral density, fracture risk, thromboembolic risk, cardiovascular health and ligament/tendon injury in this population. A search from the PubMed database using relevant terms was performed. Studies were included if they were levels 1–3 evidence. Due to the paucity of studies on ligament and tendon injury risk in transgender patients, levels 1–3 evidence on the effects of sex hormones in cisgender patients as well as basic science studies were included for these two topics. This review found that transgender patients on GAHT have an elevated fracture risk, but GAHT has beneficial effects on bone mineral density in transgender women. Transgender women on GAHT also have an increased risk of venous thromboembolism, stroke and myocardial infarction compared with cisgender women. Despite these elevated risks, studies have found it is safe to continue GAHT perioperatively for both transgender women and men undergoing low-risk operations. Orthopaedic and sports medicine clinicians should understand these unique health considerations for equitable patient care.
... Nota et al. 20 ...
... Prevalence studies, such as that of Wierckx et al. 17 , found no cases related to the use of GAHT. In the cohort of Asscheman et al. 10 Regarding the data of Nota et al. 20 , there was an increase in AMI compared to cis women, with an SIR of 3.69 (1.94-6.42), but no increase compared to cis men, with an SIR of 1.0 (0.53-1.74) compared to cis men. ...
... First, data from the STRONG, including a cohort of 2,133 TM, showed no significant difference between the prevalence and incidence of diabetes between the groups evaluated 25 . This may be a result of the body change brought about by masculinizing GAHT, as noted by Spanos et al. 26 Regarding cardiovascular outcomes in the TM population, VTE and stroke studies showed neutral outcomes, similar to those found in the review by Maraka et al. 10,19,20,29 There was a difference between the articles regarding the increase in AMI compared to cis women, but not in comparison to cis men, as in the data from Nota et al. 20 , which differed from those found by Getahun et al. 19 and in the review by Maraka et al. 29 This may be related to the difference in follow-up time (8.1 years in the study by Nota et al. 20 ), as well as differences in the age of the populations (younger in Getahun et al. 19 ). ...
Introduction: Transgender persons with gender dysphoria can be treated using hormones based on estradiol and testosterone. The long-term cardiovascular effects of these therapies are not fully known. Objective: To verify the impact of gender-affirming hormone therapy on risk factors for cardiovascular events (lipid profile, glucose, and blood pressure) and cardiovascular events (acute myocardial infarction [AMI], stroke, and venous thromboembolism [VTE]) in transgender persons. Methods: A systematic review of scientific articles was performed using the PubMed/MEDLINE, Scopus, Embase, and Web of Science platforms. Results and Discussion: The search resulted in 1040 articles, of which 154 duplicates were discarded. Of the remaining 886, 837 articles were excluded, leaving 49, which were read in full. Among these, after confrontation of two researchers, 14 were selected for interpretation and final data extraction. Regarding the data obtained, 11 articles considered transgender women (TW), resulting in a population of 7154 people, with a mean age of 29 years. When interpreting the results, there was an increase in VTE and stroke events in TW compared to cis men and women. The cardiovascular risk factors did not show significant changes in the evaluated studies. Twelve studies were considered for transgender men (TM), generating a population of 4393 people, with a mean age of 26 years. A worsening of the lipid profile in TM and an increase in AMI were observed in comparison with cis women. Conclusion: Review data showed that transgender persons have a risk of increased cardiovascular outcomes and may require early intervention as a preventive measure.
... In recent years, an increasing number of gender incongruity studies have investigated cardiovascular thrombo-embolic risk related to GAHT [35][36][37][38]. A recent retrospective study [19] compared the risk of cardiovascular events between cis-and trans-gender subjects. ...
... The CV event incidence for AFAB individuals with GI was 3.7 per 1000 person-years (95 % CI: 1.4 to 10.0), while AMAB individuals with GI had a CV event incidence of 7.1 per 1000 person- [39,40]. A study by Nota et al. [37] on 3875 transgender people showed a two-fold increase in myocardial infarction among AFAB transgender people compared to cis women, but not compared to cis men, versus a two-fold increase in stroke risk and a five-fold increase in VTE risk for AMAB transgender people compared to cis men and cis women. In a cross-sectional study of 50 transgender men on T therapy for an average of 10 years, no subjects experienced myocardial infarction, stroke, or deep vein thrombosis [41]. ...
... After adjustment for CV risk factors, however, the study showed that transgender men still had a higher risk of myocardial infarction than both cisgender populations. Similar data emerged from a Dutch study of 1358 transgender men who used T, followed up for an average of 8 years: authors found three times as many heart attacks as cisgender women, with no differences compared to cisgender men and no differences in stroke occurrence compared to cisgender women or men [37]. ...
... [13][14][15][16] In contrast, feminizing hormone therapy presents an interesting paradox: while it improves blood pressure and lipid profiles, transgender women still seem to experience a higher incidence of cardiovascular events, such as stroke and myocardial infarction (MI). [17][18][19] To date, a definite explanation for this contradiction remains elusive. In addition to stroke and MI, the risk of venous thrombosis appears to be the most prominent in transgender women. ...
... In addition to stroke and MI, the risk of venous thrombosis appears to be the most prominent in transgender women. 17,18 This is in line with previous evidence from studies with cisgender women who use estradiol as oral contraceptive or hormone replacement therapy. 11,20 Alterations in coagulation factors influenced by feminizing hormone therapy could be the mechanism behind this. ...
... Finally, 22 studies were included in the review. 18, Figure 1 shows the PRISMA flow diagram of study selection. 28 ...
Objective
Hormone therapy in transgender people might be associated with an increased risk of cardiovascular disease (CVD). We aimed to investigate whether the risk of CVD is increased in transgender people compared with people of the same birth sex.
Design and methods
PubMed, Cochrane, Embase, and Google Scholar were searched until July 2022. Studies evaluating cardiovascular events in transgender women or men were included. Primary outcomes were stroke, myocardial infarction (MI), and venous thromboembolism (VTE). The risk for transgender women versus cisgender men and for transgender men versus cisgender women was analysed through random-effects meta-analysis.
Results
Twenty-two studies involving 19 893 transgender women, 14 840 transgender men, 371 547 cisgender men, and 434 700 cisgender women were included. The meta-analysis included 10 studies (79% of transgender women and 76% of transgender men). In transgender women, incidence of stroke was 1.8%, which is 1.3 (95% confidence interval [CI], 1.0-1.8) times higher than in cisgender men. Incidence of MI was 1.2%, with a pooled relative risk of 1.0 (95% CI, 0.8-1.2). Venous thromboembolism incidence was 1.6%, which is 2.2 (95% CI, 1.1-4.5) times higher. Stroke occurred in 0.8% of transgender men, which is 1.3 (95% CI, 1.0-1.6) times higher compared with cisgender women. Incidence of MI was 0.6%, with a pooled relative risk of 1.7 (95% CI, 0.8-3.6). For VTE, this was 0.7%, being 1.4 (95% CI, 1.0-2.0) times higher.
Conclusions
Transgender people have a 40% higher risk of CVD compared with cisgender people of the same birth sex. This emphasizes the importance of cardiovascular risk management. Future studies should assess the potential influence of socio-economic and lifestyle factors.
... Among TGD adults with normal cardiac anatomy, transgender women on estradiol therapy have an increased risk of venous thromboembolism (VTE), ischemic cerebrovascular accident, and myocardial infarction compared with cisgender women and increased risk of VTE compared with cisgender men. [12][13][14][15][16] In transgender men, data on myocardial infarction compared with cisgender women are mixed, 13,15,16 there is no increased risk of myocardial infarction compared with cisgender men, 13,15,16 and no differences in VTE, cerebrovascular accident, or diabetes compared with either cisgender men or women. [13][14][15][16] The American Heart Association (AHA) recently published a Scientific Statement summarizing these cardiovascular concerns, also recognizing the psychosocial and behavioral components of excess morbidity and mortality including tobacco and substance use, glycemic control, obesity, and social stigma, which should be studied via an intersectional, multilevel minority stress model. ...
... Among TGD adults with normal cardiac anatomy, transgender women on estradiol therapy have an increased risk of venous thromboembolism (VTE), ischemic cerebrovascular accident, and myocardial infarction compared with cisgender women and increased risk of VTE compared with cisgender men. [12][13][14][15][16] In transgender men, data on myocardial infarction compared with cisgender women are mixed, 13,15,16 there is no increased risk of myocardial infarction compared with cisgender men, 13,15,16 and no differences in VTE, cerebrovascular accident, or diabetes compared with either cisgender men or women. [13][14][15][16] The American Heart Association (AHA) recently published a Scientific Statement summarizing these cardiovascular concerns, also recognizing the psychosocial and behavioral components of excess morbidity and mortality including tobacco and substance use, glycemic control, obesity, and social stigma, which should be studied via an intersectional, multilevel minority stress model. ...
... Among TGD adults with normal cardiac anatomy, transgender women on estradiol therapy have an increased risk of venous thromboembolism (VTE), ischemic cerebrovascular accident, and myocardial infarction compared with cisgender women and increased risk of VTE compared with cisgender men. [12][13][14][15][16] In transgender men, data on myocardial infarction compared with cisgender women are mixed, 13,15,16 there is no increased risk of myocardial infarction compared with cisgender men, 13,15,16 and no differences in VTE, cerebrovascular accident, or diabetes compared with either cisgender men or women. [13][14][15][16] The American Heart Association (AHA) recently published a Scientific Statement summarizing these cardiovascular concerns, also recognizing the psychosocial and behavioral components of excess morbidity and mortality including tobacco and substance use, glycemic control, obesity, and social stigma, which should be studied via an intersectional, multilevel minority stress model. ...
Background
Transgender and gender diverse (TGD) individuals and long‐term survivors with adult congenital heart disease (ACHD) are both growing populations with specialized needs. No studies assess temporal trends or evaluate the care of TGD individuals with ACHD.
Methods and Results
Meetings between congenital cardiology and gender‐affirming care specialists identified unique considerations in TGD individuals with ACHD. A retrospective chart review was then performed to describe patient factors and outpatient trends in those with an ACHD diagnosis undergoing gender‐affirming hormonal or surgical care (GAHT/S) at 1 adult and 1 pediatric tertiary care center. Thirty‐three TGD individuals with ACHD were identified, 21 with a history of GAHT/S. Fourteen (66%) had moderate or complex ACHD, 8 (38%) identified as transgender male, 9 (43%) transgender female, and 4 (19%) other gender identities. Three had undergone gender‐affirming surgery. There were zero occurrences of the composite end point of unplanned hospitalization or thrombotic event over 71.1 person‐years of gender‐affirming care. Median age at first gender‐affirming appointment was 16.8 years [interquartile range 14.8–21.5]. The most common treatment modification was changing estradiol administration from oral to transdermal to reduce thrombotic risk (n=3). An increasing trend was observed from zero TGD patients with ACHD attending a gender diversity appointment in 2012 to 14 patients in 2022.
Conclusions
There is a growing population of TGD patients with ACHD and unique medical and psychosocial needs. Future studies must fully evaluate the reassuring safety profile observed in this small cohort. We share 10 actionable care considerations for providers with a goal of overseeing a safe and fulfilling gender transition across all TGD patients with ACHD.
... 47 A recent larger cohort study of 2,517 transgender women from the Netherlands with a mean follow-up of 9 years shows that transgender women using GAHT had a higher incidence of MI compared to cisgender women, and a higher incidence of strokes and venous thromboembolic events compared to cisgender women and men. 48 Regarding transgender men, testosterone is the primary hormone in masculinization therapy. It aids in the development of male secondary sex characteristics, including deepening of the voice, broadening of the shoulders, and male-pattern hair growth. ...
... 46,49,50 Other studies have shown a statistically significant increase in systolic and diastolic blood pressure by 4 and 3 mmHg, respectively. 48 There are mixed results on the relationship between masculinizing GAHT and CVD. A large cross-sectional study using data from the Behavioral Risk Factor Surveillance System showed that transgender men had a twofold increase in the rate of MI compared to cisgender men and a fourfold increase compared to cisgender women. ...
Incorporating sexual orientation, gender identity, and expression (SOGIE) data into cardiovascular research design is necessary to reduce cardiovascular healthcare disparities among sexual and gender minority (SGM) people. To achieve this, researchers should not only understand appropriate terminology, but also implement inclusive survey tools that respect privacy and cultural nuances, as the benefit of obtaining SOGIE information is critical to tailoring cardiovascular interventions and ensuring equitable healthcare outcomes. In order to address potential concerns related to disclosing SOGIE information, we must prioritize sensitivity training for healthcare professionals to foster an inclusive environment for data collection, ethical considerations, and confidentiality safeguards. This review aims to develop and inform critical thinking about sex and gender and to identify strategic mechanisms to include SOGIE data in cardiovascular research, thus improving cardiovascular health outcomes for SGM individuals. By embracing a more comprehensive and inclusive approach to data collection, cardiovascular research can contribute significantly to advancing personalized and inclusive healthcare practices and medical education, and ultimately promote better health outcomes for all SGM individuals.
... Much of this risk estimation is derived from studies of cisgender women on estrogen replacement therapy. While limited studies do show increased thromboembolic risk for transgender people receiving estrogen [67,68], minority stress factors are also likely players in addition to GAHT [69]. Notably, the type of estrogen associated with the highest risk of thrombotic events is ethinyl estradiol, which the 2017 Endocrine Society Guidelines specifically recommended against using as GAHT [38]. ...
As gender diversity becomes more understood and accepted in mainstream culture, medical systems and health care providers must learn to provide comprehensive and affirming care to gender diverse individuals. As the number of gender diverse pediatric patients continues to grow, these patients will be cared for by pediatric solid‐organ transplant programs. This review summarizes the basic principles of gender‐affirming care and describes how transplant teams can provide equitable and affirming care to young gender diverse patients undergoing solid organ transplant (SOT). In addition, this review uses kidney transplant as a framework to explore gender‐affirming hormone therapy and gender‐affirming surgery in the setting of transplant, laboratory value interpretation in gender diverse individuals, and the importance of an individualized approach in care of the gender diverse transplant recipient.
... While research indicates that HRT is safe when monitored for safety risks [24], systematic studies of safety risks of hormone administration, particularly in the context of transitioning, are only beginning to surface. Evidence indicates that HRT may increase the risk of blood clots, heart attacks, strokes, and breast cancer in transgender individuals, particularly transgender women on estrogen [3,25,26,27]. Spironolactone, the testosterone blocker, may cause dehydration and negatively impact the kidneys in rare cases [28]. ...
In this editorial, I discuss the implications of the prevalence of DIY HRT practices for transgender persons, the medical ecosystem, and the relationship between the two. Drawing upon the principles of harm reduction and patient autonomy, I recommend against blanket anxieties around DIY practices, instead suggesting simultaneous bolstering of efforts to bridge the gap between transgender people and medical practitioners, and the wide dissemination of HRT-related knowledge to transgender people, particularly those further marginalised by poverty and a lack of formal education.
... Cinsiyet geçişi için hormon tedavisi alan trans kadınlarda, cis kadın ve cis erkeklere göre inme ve venöz tromboembolizm insidansı daha fazladır [21] . Ayrıca östrojen tedavisi ilaçların metabolizmasını etkileyen bazı sitokrom enzimle-rinin aktivitelerini de değiştirebilmektedir [22] . ...
Antiretroviral tedavi (ART) etkinliğinin geliştirilmesi insan immün yetmezlik virüsü [human immunodeficiency virüs (HIV)] ile yaşayan bireylerde (HİYB) beklenen yaşam süresini iyileştirmiştir. Bu durum kronik komorbiditeler ve geriatrik sendromların gelişimi için risk taşıyan ve yaşlanan HİYB sayısında artışla sonuçlanmıştır. İnsan immün yetmezlik virüsü infeksiyonu ve eşlik eden komorbiditelerin bir sonucu olarak HİYB'lerde artan ilaç yükü, hasta ile ilişkili sonuçları olumsuz etkilemektedir. İnsan immün yetmezlik virüsü ile yaşayan bireylerin ilaç yükünü azaltmak için ilaç rejimlerinin bireyselleştirilmesi ve bireylerin sağlık durumları, tedavi hedefleri ve tedavi tercih-lerine göre ilaç sayılarının azaltılması önerilmektedir. Bu derlemede HİYB'lerde artan ilaç yükünün ve bu ilaç yükünün azaltılmasına yönelik yaklaşımların tartışılması amaçlanmıştır.
... This hormonal therapy not only changes the gender identity of the person undergoing hormonal therapy but also has many adverse effects, such as cardiovascular diseases, thromboembolism, and liver dysfunction (9,12). Estrogen has been found to cause granulomatous mastitis and venous thromboembolism in tanswomen (13,14). Similarly, in transmen, testosterone may cause vaginal bleeding, which is a severe complication after initiation of cross-sex hormone therapy. ...
People who change their gender after birth are known as transgender people. They underwent surgical transformation along with hormonal therapy. Hormonal imbalance is the most common phenomenon in the transgender community due to hormonal therapy and other related issues. Hormonal therapy is essential for gender transformation, but this therapy poses several risks to the individual who is taking this therapy. Transgender people who are under hormonal therapy are more at risk of cardiovascular disorders as certain hormones like estrogen and testosterone, besides their intended function, also induce side effects, due to which individuals taking these hormones become more prone to cardiovascular disorder, irregular blood pressure, brain function, and structure start changing. The cross-sex hormone therapy is also associated with brain tumors, changes in body mass index, and several skin conditions. Such hormones also affect bone density in different individuals due to changes in the deposition pattern of calcium into the bone under hormonal control. Hormonal therapy causes certain metabolic disorders as well, and certain hormones interact with other hormones in a different way when they are not naturally produced in the body. The voice of such people undergoing gender transformation also changes due to the testosterone level. This review summarizes some aspects of hormonal therapy, but whether or not a person undergoes such transition is their choice.
... Tras años de trabajo, la antigua presidenta del Royal College of Paediatrics and Child Health confirma la presencia de serios problemas relacionados con este enfoque afirmativo. Varias son las principales objeciones: a) la transición social está lejos de ser un proceso inocuo y reversible, ya que actúa como un tratamiento psicosocial que eleva significativamente las probabilidades de que el joven continúe con las demás fases de la intervención (31) sin estar claro que contribuya al bienestar del menor (32,33) ; b) no sabemos hasta qué punto mejora la salud mental de los jóvenes (34)(35)(36) , en especial en relación con índices tan importantes como la conducta suicida (37)(38)(39) ; c) desconocemos cuántos desistidores y destransicionadores hay (40)(41)(42) , aunque algunos autores prevén que serán más de lo que parece (43,44) ; d) no están claros los efectos médicos del consumo crónico de bloqueadores de la pubertad y hormonas cruzadas en áreas como la salud cardiovascular (45,46) o la densidad ósea (47,48) ; y e) en contra de investigaciones que señalan que las disforias de género adolescentes se superan sin intervención en una amplia mayoría de los casos (49,50) , la terapia afirmativa cuenta con tasas bajas de abandono y una vez iniciada no parece fácil su interrupción (51) -recordemos que no existe una edad mínima para el inicio de la primera fase-. Quizá el mejor resumen de toda esta cuestión lo han ofrecido recientemente Levine et al (52) al señalar que la ratio beneficios/riesgos de la terapia afirmativa se mueve entre lo desconocido y lo desfavorable: 'las preguntas sobre el mejor tratamiento para el creciente número de jóvenes disfóricos con su género producen una división tan intensa dentro y fuera de la medicina que pocas veces hemos visto ante otras dudas clínicas […] Debemos dejar de usar argumentos que hablan de la justicia social y volver a los honorables principios de la medicina basada en la evidencia'. ...
Los países occidentales están contemplando un incremento muy notable de problemas de disforia de género y transexualidad/transgenerismo, con perfiles demográficos de edad y sexo bien definidos. No está claro que el abordaje farmacoquirúrgico que habitualmente se dispensó a los fenómenos de la transexualidad en el pasado sea el más adecuado para esta nueva ola de malestares. Recordando la importante distinción entre forma y función de una conducta – que define el enfoque psicológico–, se defiende que la gran mayoría de los nuevos casos de disforia que se atienden en las unidades de identidad de género actuales son un fenómeno de naturaleza psicológica, fruto de la influencia social y favorecido por múltiples factores, entre los que destacan una sociedad individualista, subjetivista e irracionalista; una filosofía posmoderna que niega los conceptos de verdad, realidad y ciencia; la apertura de los centros educativos a tales planteamientos; los medios de comunicación; las redes sociales; el uso demagógico de estas personas en las disputas políticas; y un importante nicho de mercado, no sólo médico.
... More recently, clinicians, scientists, and the general public have been increasingly questioning some of the existing practices and standards of care for children and adolescents presenting with gender dysphoria [6,18,20,[24][25][26]. Research found some serious health consequences of puberty blockers and cross-sex hormones, particularly when treatments are started in minors [27][28][29][30][31][32][33]. There have also been several examples of non-adherence to the core professional and medico-ethical principles when providing care for gender dysphoric children and adolescents in some countries [25,[34][35][36][37][38][39][40][41][42][43][44][45]. ...
ESCAP firmly believes that there is an urgent need to apply widely endorsed clinical, scientific, and ethical standards to the care of children and adolescents with gender dysphoria. It is important to base decisions for possible medical transitions on a rigorous assessment of individual needs and their capacity to consent regarding the serious long-term consequences of these treatments. Long-term follow-up studies are urgently needed to better understand both the natural course of gender dysphoria in the absence of medical treatment and the consequences of medical transition. A clinical research framework with patient and public involvement should be established and promoted at the European level to facilitate relevant research. The standards of evidence-based medicine must ensure the best and safest possible care for each individual in this highly vulnerable group of children and adolescents. As such, ESCAP calls for healthcare providers not to promote experimental and unnecessarily invasive treatments with unproven psycho social effects and, therefore, to adhere to the "primum-nil nocere" (first, do no harm) principle. Finally, ESCAP insists that respect for all kinds of different views and attitudes is an essential part of an ongoing open professional debate that we wish to stimulate.
... A systematic review and meta-analysis evaluating various cardiovascular outcomes concluded that a longer duration of gender-affirming testosterone therapy is associated with undesirable effects on the lipid profile but recognizes the potential for confounding variables that were not consistently reported in the studies it drew from, such as smoking history, testosterone dosage and formulations used. 11 Similarly, the effects of testosterone therapy on diabetes mellitus risk and blood pressure are areas with conflicting evidence. 10 This inconsistency in data highlights the need for more robust and longitudinal studies to better understand the long-term implications of testosterone therapy. ...
... 54,55 Furthermore, although evidence is still limited, transgender women receiving GAT seem to have an increased risk of cerebrovascular accidents compared to both assigned at birth males and females. 53,55,56 Most of studies on transgender men did not report a sufficiently high number of events to allow a reliable comparison, 57,58 suggesting that the risk of MI in transgender men is an overall rare event. However, a Dutch retrospective study did not observe an increased incidence of MI between transgender men and the general population, whereas a cross-sectional population-based study observed an increased risk of MI in comparison with both cisgender males and females. ...
Background
Personalized medicine represents a novel and integrative approach that focuses on an individual's genetics and epigenetics, precision medicine, lifestyle and exposures as key players of health status and disease phenotypes.
Methods
In this narrative review, we aim to carefully discuss the current knowledge on gender disparities in cardiometabolic diseases, and we consider the sex‐ specific expression of miRNAs and their role as promising tool in precision medicine.
Results
Personalised medicine overcomes the restricted care of patient based on a binomial sex approach, by enriching itself with a holistic and dynamic gender integration. Recognized as a major worldwide health emergency, cardiometabolic disorders continue to rise, impacting on health systems and requiring more effective and targeted strategies. Several sex and gender drivers might affect the onset and progression of cardiometabolic disorders in males and females at multiple levels. In this respect, distinct contribution of genetic and epigenetic mechanisms, molecular and physiological pathways, sex hormones, visceral fat and subcutaneous fat and lifestyle lead to differences in disease burden and outcomes in males and females.
Conclusions
Sex and gender play a pivotal role in precision medicine because the influence the physiology of each individual and the way they interact with environment from intrauterine life.
... C ardiovascular disease (CVD) is more common in cisgender men than in cisgender women, indicating that sex hormones have an influential effect on cardiovascular health. 1 Greater numbers of cardiovascular-related deaths have been reported among transgender adults, with an increased risk of myocardial infarction in both transgender women and transgender men compared with the general female population. 2,3 Gender-affirming hormone treatment (GAHT) has been shown to influence modifiable risk factors for CVD. 4,5 Metabolic syndrome (MetS) comprises a cluster of cardiovascular risk factors that may occur in adults with obesity. ...
Purpose: The objective of this study was to examine the association of designated sex at birth, body composition, and gender-affirming hormone treatment (GAHT) with the components of metabolic syndrome (MetS) (overweight/obesity, elevated blood pressure [BP], altered glucose metabolism, and dyslipidemia) in transgender/gender diverse (TGD) adolescents and young adults. Methods: TGD individuals underwent body composition studies by bioelectrical impedance analysis according to designated sex at birth, and their muscle-to-fat ratio (MFR) z-scores were calculated. Generalized estimating equations with binary logistic models (n = 326) were used to explore associations while adjusting for potential confounders. Results: A total of 55 TGD females and 111 TGD males, with mean age of 18 ± 1.9 years and median duration of GAHT of 1.4 years (interquartile range = 0.6-2.5), were enrolled. Overall, 118/166 (71%) of the TGD cohort showed evidence of at least one MetS component, with a significantly higher rate among TGD males compared with TGD females (91.1% vs. 50.9%, p < 0.001). TGD males were at increased odds for overweight/obesity, elevated/hypertensive BP, elevated triglycerides (TGs), and an atherogenic dyslipidemia index (TG/high-density lipoprotein cholesterol [HDL-c], TG:HDL-c). The odds of overweight/obesity increased by 44.9 for each standard deviation decrease in the MFR z-score, while the odds for an elevated TG:HDL-c index increased by 3.7. Psychiatric morbidity increased the odds for overweight/obesity by 2.89. Conclusions: After considering confounding variables, the TGD males on GAHT were found to be at an increased risk for cardiometabolic disease. Our observations support the importance of targeted medical nutrition intervention in this group of individuals.
... D'altra parte, mancano dati esaustivi sulla sicurezza cardiovascolare a lungo termine in questa popolazione [4], per cui sarebbero necessari studi prospettici a lungo termine. Nelle persone trans/GD AMAB, la terapia con estrogeni comporta un assetto più pro-coagulativo, che potrebbe contribuire all'aumentata incidenza di episodi di tromboembolismo venoso [17][18][19]. Inoltre, nelle persone AMAB che non hanno (ancora) intrapreso la terapia ormonale è descritta una densità minerale ossea ridotta rispetto alle persone cisgender di uguale genere assegnato alla nascita; tuttavia, la terapia ormonale femminilizzante è associata a un miglioramento dei valori densitometrici, soprattutto a livello lombare [20]. In merito al rischio oncologico, insieme al CPA, anche la terapia con estrogeni potrebbe essere associata a un lieve rischio di iperprolattinemia [2]. ...
Sommario
La terapia ormonale di affermazione di genere ha la finalità di allineare, per quanto possibile, le caratteristiche corporee con l’identità di genere e gli specifici obiettivi delle persone transgender (trans) o gender diverse (GD) che ne esprimano la necessità. Il cardine della terapia virilizzante e de-femminilizzante nelle persone trans/GD assegnate al genere femminile alla nascita (AFAB) è rappresentato dal testosterone (T), in grado di indurre modificazioni corporee quali l’amenorrea, l’aumento della distribuzione pilifera del corpo e del volto, l’aumento della massa muscolare, l’abbassamento del timbro vocale, l’aumento delle dimensioni del clitoride. L’acne, l’alopecia con pattern maschile, la policitemia e il peggioramento dell’assetto lipidico sono i principali effetti collaterali della terapia con T, che richiede un attento monitoraggio clinico-biochimico. Alcune persone trans/GD AFAB desiderano una mascolinizzazione e/o de-femminilizzazione parziale, per cui potrebbero essere proposte terapie con dosaggi ridotti di T in associazione ad altre strategie non ormonali di affermazione di genere, valutando il rapporto tra benefici e possibili rischi di tale trattamento. La terapia femminilizzante e de-mascolinizzante nelle persone trans/GD assegnate al genere maschile alla nascita (AMAB) si basa sull’uso di estrogeni (in varie formulazioni) e antiandrogeni, nella fattispecie ciproterone acetato (CPA), analoghi dell’ormone di rilascio delle gonadotropine (GnRHa) o, in alternativa, spironolattone. Tra i principali effetti attesi della terapia con estrogeni e antiandrogeni, sono previsti l’aumento del volume mammario, la riduzione della distribuzione pilifera del volto e del corpo, dell’oleosità della cute, delle erezioni spontanee e del volume testicolare e la ridistribuzione del grasso corporeo in aree ginoidi. La terapia con estrogeni può essere associata a un aumentato rischio di tromboembolismo venoso, mentre la terapia con antiandrogeni è associata a specifici – per quanto rari – effetti collaterali che impongono un regolare monitoraggio clinico e biochimico. Alcune persone trans/GD AMAB potrebbero richiedere una terapia finalizzata alla parziale femminilizzazione e/o de-mascolinizzazione del corpo; pertanto, può essere presa in considerazione una terapia con bassi dosaggi di estrogeni e/o di antiandrogeni secondo gli specifici obiettivi della persona, effettuando un bilancio tra benefici e rischi, soprattutto sotto il profilo della salute ossea e cardiovascolare.
... 5,9 Despite the low usage of DOR-and NNRTI-based regimens in 2020 (1% and 11% of persons living with HIV are prescribed ARV therapy, respectively), the metabolic profile of DOR is favorable to patients with dyslipidemias, especially for TGW, as they are at an increased risk for cardiovascular events due to HIV-1 infection and hormone therapy. [10][11][12][13][14][15] The effects of chronic estradiol in TGW on ARV clearance mechanisms are not well understood. Chronic estradiol elevations have been shown to upregulate expression of transcription factors, resulting in the induction of CYP enzymes. ...
Transgender women may have concerns of drug interactions between feminizing hormone therapy (FHT) and antiretrovirals, leading to nonadherence. This randomized, three‐period crossover, open‐label, phase I trial assessed the effects of doravirine (DOR) and tenofovir disoproxil fumarate (TDF) on the pharmacokinetics (PKs) of estradiol, spironolactone, and total testosterone and vice versa in healthy transgender women. Volunteers were randomized 1:1 into two sequences containing three treatment groups (DOR, lamivudine [3TC], and TDF alone; estradiol, spironolactone, and placebo; and DOR/3TC/TDF, estradiol, and spironolactone). Eight subjects enrolled in the study and six had completed all study periods. The geometric mean ratios for DOR area under the concentration‐time curve from zero to last measured concentration (AUC 0‐last ), maximum concentration ( C max ), and concentration at 24 h ( C 24 ) were similar. However, tenofovir (TFV) AUC 0‐last , C max , and C 24 moderately increased by 14%–38%. Last, estradiol AUC 0‐last , C max , and C 24 were increased by 10%–13%. Whereas most 90% confidence intervals did not meet the bioequivalence bounds of 80%–125%, the point estimates fell within the intervals. Log‐transformed DOR, TFV, and estradiol PK parameters computed with and without co‐administration were not statistically different ( p > 0.05). There were no serious adverse events. There is not a clinically significant impact of FHT on DOR/TFV PKs. Similarly, there is no observed impact on estradiol PKs and total testosterone following use of DOR/3TC/TDF.
... Large retrospective series comparing transgender individuals AFAB with historical cohorts of cisgender women reported that GAHT is associated with an increased risk of mortality without an increase of cardiovascular events in up to 11 years [22,23]. However, a large-scale study with a similar methodology found that the risk of myocardial infarction was increased in transgender men receiving GAHT for a mean duration of 8 years [26]. Importantly, all studies to date, including ours, assessed relatively young individuals who may not reach an age where cardiovascular events typically occur even after two or three decades of GAHT. ...
Purpose
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. We aimed to investigate the prevalence and phenotypic characteristics of PCOS in testosterone treatment-naïve transgender people assigned female at birth (AFAB), as well as to determine whether cardiometabolic risk factors vary based on the presence of PCOS and its components.
Methods
Evaluation of 112 testosterone treatment-naïve transgender adults AFAB for PCOS and its individual components, including androgen excess, ovulatory dysfunction and polycystic ovarian morphology (PCOM).
Results
In our cohort, 79.5% of transgender individuals AFAB had at least one component of PCOS. The prevalence of PCOS was 38.4% (43/112). Phenotype C was the most common phenotype (17.8%), followed by phenotype B (10.7%). Transgender individuals AFAB with at least one component of PCOS had higher blood pressure (BP) measurements and higher fasting plasma glucose levels compared to those with none. Sixty-one subjects (54%) had hyperandrogenism (HA), with 20 (17.9%) having HA without other components of PCOS. When compared to those without HA, transgender individuals AFAB with HA had higher body mass index (BMI), BP, triglyceride and lower HDL-cholesterol levels.
Conclusion
PCOS and androgen excess appear to be prevalent among transgender people AFAB. Transgender individuals AFAB with HA or PCOS may exhibit an unfavorable cardiometabolic risk profile compared to those without any PCOS component. Assessment of androgen excess and the specific components of PCOS at baseline could inform long-term management.
... In addition to an influence of sex hormones on cognitive functioning, mental and physical health aspects such as depression and hypertension are known to be associated with cognitive impairment (Brailean et al., 2017;Gorelick, 2018;Knight & Baune, 2018). Also, (older) transgender individuals have more mental health challenges and a higher cardiovascular risk (CVR) compared to the general population (Fredriksen-Goldsen et al., 2014;Getahun et al., 2018;Hoy-Ellis et al., 2017;Irwig, 2018;Nota et al., 2019). Hence, these factors are important to consider when studying cognitive functioning in transgender individuals. ...
... Although meta-analytic approaches concluded that no cardiovascular complications have been recorded during GAHT, the evidences available in the literature are still scarce to define GAHT as definitively safe in terms of cardiovascular health [45]. Overall, the myocardial Infarction risk is demonstrated to be similar between cisgender males and transgender AFAB people [46,47] without an increased morbidity and mortality for cardiovascular reasons during GAHT [10]. On the contrary, the myocardial infarction risk seems to be higher in transgender AFAB people compared to cisgender women [47]. ...
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.
In many parts of the world, increasing numbers of transgender and gender diverse (TGD) youth are seeking medical services to enable the development of physical characteristics aligned with their gender identities. Such medical services include use of agents to pause endogenous puberty as early as Tanner stage 2 with subsequent use of gender-affirming sex hormones and are based on longitudinal studies, demonstrating that those individuals who were first identified as gender dysphoric in early or middle childhood and continue to meet the mental health criteria for gender incongruence at early puberty are likely to persist in their gender identities as adults. This chapter addresses terms and definitions applicable to TGD youth, studies that shed light on the biologic underpinnings of gender identity, outcomes and potential complications of current treatment models, gaps in knowledge, and priorities for research.
Research regarding the hematologic sequelae of estrogen and testosterone therapy for transgender people is an emerging area. While estrogen therapy has been widely studied in cisgender women, studies in transgender individuals are limited, revealing variable adverse effects influenced by the dose and formulation of estrogen used. Thrombotic risk factors in transgender and gender-diverse individuals are multifactorial, involving both modifiable and nonmodifiable factors. Management of venous thromboembolism (VTE) in individuals receiving gender-affirming estrogen entails standard anticoagulation therapy alongside shared decision-making regarding hormone continuation and risk factor modification. While data and guidance from cisgender women can offer a reference for managing thrombotic risk in transgender individuals on hormone therapy, fully applying these insights can be challenging. The benefits of gender-affirming hormone therapy include significantly reducing the risk of suicide and depression, highlighting the importance of a contemplative approach to the management of hormonal therapy after a VTE event. Although limited, the available data in the literature indicate a low thrombotic risk for transgender individuals undergoing gender-affirming testosterone therapy. However, polycythemia is a common adverse effect necessitating monitoring and, occasionally, adjustments to hormonal therapy. Additionally, iron deficiency may arise due to the physiological effects of testosterone or health care providers' use of phlebotomy, an aspect that remains unstudied in this population. In conclusion, while the set of clinical data is expanding, further research remains vital to refine management strategies and improve hematologic outcomes for transgender individuals undergoing gender-affirming hormone therapy.
AIM
The “2024 Guideline for the Primary Prevention of Stroke” replaces the 2014 “Guidelines for the Primary Prevention of Stroke.” This updated guideline is intended to be a resource for clinicians to use to guide various prevention strategies for individuals with no history of stroke.
METHODS
A comprehensive search for literature published since the 2014 guideline; derived from research involving human participants published in English; and indexed in MEDLINE, PubMed, Cochrane Library, and other selected and relevant databases was conducted between May and November 2023. Other documents on related subject matter previously published by the American Heart Association were also reviewed.
STRUCTURE
Ischemic and hemorrhagic strokes lead to significant disability but, most important, are preventable. The 2024 primary prevention of stroke guideline provides recommendations based on current evidence for strategies to prevent stroke throughout the life span. These recommendations align with the American Heart Association’s Life’s Essential 8 for optimizing cardiovascular and brain health, in addition to preventing incident stroke. We also have added sex-specific recommendations for screening and prevention of stroke, which are new compared with the 2014 guideline. Many recommendations for similar risk factor prevention were updated, new topics were reviewed, and recommendations were created when supported by sufficient-quality published data.
Research in Europe supports that trans and non-binary people face stigma and discrimination in all aspects of their everyday lives. Still, there are no similar studies conducted in Greece, related statistics and research findings are outdated. This study examines the experiences of transgender (trans) and non-binary individuals with medical professionals in Greece. The study's objectives are to investigate medical doctors' attitudes towards transgender and non-binary individuals, explore these individuals' subjective experiences with healthcare professionals, and contribute data on their health outcomes. The methodology consists of a mixed methods approach. A survey, including demographic questions and items on LGBT+ education and attitudes, was distributed online to 248 medical doctors. The data were analyzed using multiple regression to assess attitudes and experiences of discrimination, violence, and harassment towards transgender individuals. The analysis showed significant transphobic attitudes. Semi-structured interviews of trans and non-binary people were conducted and analyzed using thematic analysis. The study delves into the struggles of trans and non-binary individuals in Greece's healthcare, highlighting discrimination and medical biases that lead to poor health outcomes. It notably emphasizes the underexplored experiences of non-binary people, bridging a gap in the existing research.
Background and Aims
The role of gender in decision-making for oral anticoagulation in patients with atrial fibrillation (AF) remains controversial.
Methods
The population cohort study used electronic healthcare records of 16 587 749 patients from UK primary care (2005–2020). Primary (composite of all-cause mortality, ischaemic stroke, or arterial thromboembolism) and secondary outcomes were analysed using Cox hazard ratios (HR), adjusted for age, socioeconomic status, and comorbidities.
Results
78 852 patients were included with AF, aged 40–75 years, no prior stroke, and no prescription of oral anticoagulants. 28 590 (36.3%) were women, and 50 262 (63.7%) men. Median age was 65.7 years (interquartile range 58.5–70.9), with women being older and having other differences in comorbidities. During a total follow-up of 431 086 patient-years, women had a lower adjusted primary outcome rate with HR 0.89 vs. men (95% confidence interval [CI] 0.87–0.92; P < .001) and HR 0.87 after censoring for oral anticoagulation (95% CI 0.83–0.91; P < .001). This was driven by lower mortality in women (HR 0.86, 95% CI 0.83–0.89; P < .001). No difference was identified between women and men for the secondary outcomes of ischaemic stroke or arterial thromboembolism (adjusted HR 1.00, 95% CI 0.94–1.07; P = .87), any stroke or any thromboembolism (adjusted HR 1.02, 95% CI 0.96–1.07; P = .58), and incident vascular dementia (adjusted HR 1.13, 95% CI 0.97–1.32; P = .11). Clinical risk scores were only modest predictors of outcomes, with CHA2DS2-VA (ignoring gender) superior to CHA2DS2-VASc for primary outcomes in this population (receiver operating characteristic curve area 0.651 vs. 0.639; P < .001) and no interaction with gender (P = .45).
Conclusions
Removal of gender from clinical risk scoring could simplify the approach to which patients with AF should be offered oral anticoagulation.
Background
The risk of venous thromboembolism (VTE) with gender‐affirming hormone therapy (GAHT) in transgender and gender non‐binary (TNB) youth is unclear.
Objective
To identify the rate of VTE in a cohort of TNB youth followed in the transgender health clinic at Boston Children's Hospital, and to investigate the impact of congenital thrombophilia diagnosis on the use of GAHT.
Methods
ICD‐9 and ICD‐10 codes were used to identify eligible individuals, defined as (i) having a diagnosis of gender dysphoria and (ii) venous thromboembolism (VTE). Data were abstracted from a review of medical records. A second data query assessed TNB individuals who had an associated thrombophilia diagnosis.
Results
The primary analysis included 1860 individuals. Total 942 individuals (50.6%) had started GAHT at the time of data analysis. Mean age (±SD) at GAHT initiation was 16.8 (±1.9) years. Five thrombotic events were identified in three (0.13%) individuals, all in the setting of additional VTE risk factors. Only two of five thrombotic events occurred while receiving GAHT. The rate of VTE in the GAHT cohort did not statistically differ from the rate of VTE in the non‐GAHT cohort (0.1% vs. 0.2%, p = .62). Of the 10 individuals diagnosed with a congenital thrombophilia, two transmasculine individuals received prophylactic anticoagulation prior to GAHT. No VTE has been reported to date in this cohort.
Conclusions
In our cohort, VTE was rare in the TNB youth and was not associated with GAHT use. TNB youth with congenital thrombophilia have not developed VTE in the setting of GAHT use to date.
Gender-affirming hormone therapy (GAHT) is used by many transgender and gender-diverse adults to align physical characteristics with their gender identity, reduce gender incongruence and improve psychological functioning. This narrative review provides an overview of the initiation and monitoring of GAHT in an Australian context. Trans individuals treated with testosterone typically receive standard testosterone doses and formulations recommended for cisgender men, whereas those receiving estradiol GAHT are typically treated with estradiol in combination with an anti-androgen in those without orchidectomy. Proactive monitoring and mitigation of cardiovascular risk factors is pertinent in all transgender and gender-diverse adults and bone health is an important consideration in those using estradiol GAHT.
Introduction
The objective of this document is to guide best practice to ensure the safety and dignity of transgender and gender‐diverse people in the peri‐operative period. While transgender and gender‐diverse people may have specific health needs in relation to gender dysphoria, their health requirements go beyond their gender identity. Most doctors will provide care to someone who is transgender or gender‐diverse at some stage in their career. It is therefore important that all anaesthetists are educated on specific considerations when caring for these patients.
Methods
A working party was assembled consisting of individuals with experience in direct clinical care of the relevant patient group, those who have expertise in endocrinology and gender‐affirming hormones, educators on the topic of transgender and gender‐diverse healthcare, and authors of both cisgender and transgender identities. After discussion among the working party, targeted searches of literature were undertaken.
Results
The authors initially came up with a list of over 25 recommendations which was subsequently revised to a list of 15 recommendations after further review by the working party. These included airway assessment and management; management of hormonal therapy; relevant issues in obstetric anaesthesia; and hospital infrastructure and processes.
Conclusions
This document provides the first guidance produced to advise on best practice to ensure the safety and dignity of trans and gender‐diverse individuals in the peri‐operative period.
BACKGROUND
Transgender and nonbinary individuals face substantial cardiovascular health uncertainties. The use of gender-affirming hormone therapy can be used to achieve one’s gender-affirming goals. As self-rated health is an important predictor of health outcomes, an understanding of how this association is perceived by transgender and nonbinary individuals using gender-affirming hormone therapy is required. The objective of this research was to explore transgender and nonbinary individuals’ perceptions of cardiovascular health in the context of using gender-affirming hormone therapy.
METHODS
In this qualitative study, English-speaking transgender and nonbinary adults using gender-affirming hormone therapy for 3 months or more were recruited from across Canada using purposive and snowball sampling methods. Semistructured interviews were conducted through videoconference to explore transgender and nonbinary individuals’ perceptions of the association between gender-affirming hormone therapy and cardiovascular health between May and August 2023. Data were transcribed verbatim, and transcripts were analyzed independently by 3 reviewers using thematic analysis.
RESULTS
Twenty-one participants were interviewed (8 transgender women, 9 transgender men, and 3 nonbinary individuals; median [range] age, 27 [20–69] years; 80% White participants). Three main themes were identified: cardiovascular health was not a primary concern in the decision-making process with regard to gender-affirming hormone therapy, the improved well-being associated with gender-affirming hormone therapy was felt to contribute to improved cardiovascular health, and health care provider knowledge and attitude facilitate the transition process.
CONCLUSIONS
Gender-affirming hormone therapy in transgender and nonbinary individuals is perceived to improve cardiovascular health. Given the positive associations between care aligned with patient priorities, self-rated health, and health outcomes, these findings should be considered as part of shared decision-making and person-centered care.
Der Artikel gibt aus klinischer Perspektive und in Würdigung der komplexen und teilweise widersprüchlichen Entwicklungen innerhalb des medizinischen Versorgungssystems in Deutschland einen Überblick über die Veränderungen der letzten Jahre im Kontext trans*. Im Fokus stehen dabei insbesondere die divergenten Zielsetzungen der medizinzentrierten Kategorisierungssysteme wie ICD-10, ICD-11 und DSM-5 zur Erfassung des Begriffes trans* gegenüber sozialen Strömungen deren Diversität trans* in Richtung eines Freiheitsbegriffs individuell empfundener Geschlechtlichkeit auflöst. Diese Divergenzen treten in Deutschland insbesondere bei der Frage geschlechtsangleichender Maßnahmen über die das gesamte Spektrum von trans* Personen hinweg hervor, da sich als nicht-binär definierende Personen derzeit nicht auf die Übernahme der Kosten der Maßnahmen durch die gesetzlichen Krankenkassen berufen können. Mit der Definition von drei unterschiedlichen Gruppen von trans* Personen wird versucht, aus klinischer Sicht ärztliche und psychotherapeutische Verantwortung für diese Patient*innen innerhalb des komplexen Bedingungsgefüges medizinischer Versorgung in Deutschland zu strukturieren und Impulse im Sinne einer partizipativen Behandlungsplanung zu geben.
Context
The plasma metabolome is a functional readout of metabolic activity and is associated with phenotypes exhibiting sexual dimorphism, such as cardiovascular disease. Sex hormones are thought to play a key role in driving sexual dimorphism.
Objective
Gender-affirming hormone therapy (GAHT) is a cornerstone of transgender care, but longitudinal changes in the plasma metabolome with feminizing GAHT have not been described.
Methods
Blood samples were collected at baseline and after 3 and 6 months of GAHT from transgender women (n = 53). Participants were randomized to different anti-androgens, cyproterone acetate or spironolactone. Nuclear magnetic resonance-based metabolomics was used to measure 249 metabolic biomarkers in plasma. Additionally, we used metabolic biomarker data from an unrelated cohort of children and their parents (n = 3748) to identify sex- and age-related metabolite patterns.
Results
We identified 43 metabolic biomarkers altered after 6 months in both anti-androgen groups, most belonging to the very low- or low-density lipoprotein subclasses, with all but 1 showing a decrease. We observed a cyproterone acetate-specific decrease in glutamine, glycine, and alanine levels. Notably, of the metabolic biomarkers exhibiting the most abundant “sex- and age-related” pattern (higher in assigned female children and lower in assigned female adults, relative to assigned males), 80% were significantly lowered after GAHT, reflecting a shift toward the adult female profile.
Conclusion
Our results suggest an anti-atherogenic signature in the plasma metabolome after the first 6 months of feminizing GAHT, with cyproterone acetate also reducing specific plasma amino acids. This study provides novel insight into the metabolic changes occurring across feminizing GAHT.
Objective:
Participation in athletics is essential for the overall well-being of transgender athletes and should be included as part of gender-affirming care. Surveys show physicians and athletic trainers want to provide appropriate care for transgender athletes but lack the proper knowledge and training to do so. Gender Affirming Hormone Therapy (GAHT) is part of gender-affirming care, yet the effects of GAHT on the cardiovascular and musculoskeletal health of transgender athletes is not well-understood. The purpose of this review was to discuss important musculoskeletal and cardiovascular considerations unique to transgender athletes and improve physician understanding in caring for transgender athletes.
Methods:
A representative selection of literature on the effects of GAHT on cardiovascular and musculoskeletal health was included in this review.
Results:
Estrogen therapy may increase the risk of venous thromboembolism (VTE) and stroke, and decrease blood pressure levels among transgender women, while studies on lipid profile are inconsistent among both transgender men and women. Transgender women receiving GAHT may also be at greater risk for bone fracture and ligamentous injuries.
Conclusion:
Exercise is essential for the well-being of transgender individuals and special considerations regarding the cardiovascular and musculoskeletal health of transgender athletes should be incorporated into standard medical education. Educational programs for transgender patients and their support team should focus on preventative measures that can be taken to reduce the risk of adverse musculoskeletal and cardiovascular events. The PPE is an invaluable tool available to physicians to monitor the health and safety of transgender athletes and should be regularly updated as research on the health of transgender individuals continues to grow. Longitudinal and prospective studies should examine the effects of GAHT on the musculoskeletal and cardiovascular health of transgender athletes. Lastly, health care providers play an important role in the advancement of gender-neutral policies.
A growing number of people identify as transgender and gender non-binary in the USA and worldwide. Concomitantly, an increasing number of patients are receiving gender-affirming hormone therapy (GAHT) to achieve gender congruence. GAHT has far-ranging effects on clinical and subclinical markers of cardiovascular risk. Transgender patients also appear to be at higher risk for cardiovascular diseases compared to their cisgender peers and the impact of gender-affirming therapy on cardiovascular health is unclear. Studies on the effect of GAHT on cardiovascular outcomes are confounded by differences in GAHT regimens and methodological challenges in a diverse and historically hard-to-reach population. Current cardiovascular guidelines do not incorporate gender identity and hormone status into risk stratification and clinical decision-making. In this review, we provide an overview on the cardiometabolic impact and clinical considerations of GAHT for cardiovascular risk in transgender patients.
OBJECTIVES
Guidelines for monitoring of medications frequently used in the gender-affirming care of transgender and gender-diverse (TGD) adolescents are based on studies in adults or other medical conditions. In this study, we aimed to investigate commonly screened laboratory measurements in TGD adolescents receiving gender-affirming hormone therapy (GAHT).
METHODS
TGD adolescents were recruited from 4 study sites in the United States before beginning GAHT. Hemoglobin, hematocrit, hemoglobin A1c, alanine transaminase, aspartate aminotransferase, prolactin, and potassium were abstracted from the medical record at baseline and at 6, 12, and 24 months after starting GAHT.
RESULTS
Two-hundred and ninety-three participants (68% designated female at birth) with no previous history of gonadotropin-releasing hormone analog use were included in the analysis. Hemoglobin and hematocrit decreased in adolescents prescribed estradiol (−1.4 mg/dL and −3.6%, respectively) and increased in adolescents prescribed testosterone (+1.0 mg/dL and +3.9%) by 6 months after GAHT initiation. Thirteen (6.5%) participants prescribed testosterone had hematocrit > 50% during GAHT. There were no differences in hemoglobin A1c, alanine transaminase, or aspartate aminotransferase. There was a small increase in prolactin after 6 months of estradiol therapy in transfeminine adolescents. Hyperkalemia in transfeminine adolescents taking spironolactone was infrequent and transient if present.
CONCLUSIONS
Abnormal laboratory results are rare in TGD adolescents prescribed GAHT and, if present, occur within 6 months of GAHT initiation. Future guidelines may not require routine screening of these laboratory parameters beyond 6 months of GAHT in otherwise healthy TGD adolescents.
Sexual and gender minority (LGBT+) people face unique health disparities that must be considered by health-care providers to ensure equitable and inclusive care. Although traditionally LGBT+ health has not been integrated into neurology training, sexual orientation and gender identity have direct relevance to neurological health, driven by both systemic and interpersonal factors. In this Review, we summarize the evidence for associations between sexual orientation and gender identity with the prevalence and outcomes of various neurological conditions, including neurodegenerative diseases, epilepsy, stroke and neurodevelopmental disorders, among others. We describe important clinical considerations pertaining to LGBT+ people and recommend language and practices to promote inclusive care, as well as highlight gaps in need of further research and possible strategies to minimize these, including systematic collection of sexual orientation and gender identity and use of inclusive language.
There is more discussion than ever surrounding the health and care needs of Transgender communities. However, there is limited research on the care of Transgender patients in the Intensive Care Unit which can contribute to knowledge gaps, inconsistencies and uncertainties surrounding health care practices. This article is not intended to address all of the specific needs of Transgender patients in ICU, but to explore the ethical considerations for caring for a Transgender woman in the ICU. In doing so, this article will explore some specific considerations around gender affirming care, challenging discrimination, physiological changes, and systems change to enhance care.
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