Discontinuing hormonal gender reassignment: a nationwide register study.

BACKGROUND: With increasing numbers of people seeking medical gender reassignment, the scientific community has become increasingly aware of the issue of detransitioning from social, hormonal or even surgical gender reassignment (GR). This study aimed to assess the proportion of patients who discontinued their established hormonal gender transition and the risk factors for discontinuation. METHODS: A nationwide register-based follow-up was conducted. Data were analysed via cross-tabulations with chi-square statistics and t tests/ANOVAs. Multivariate analyses were performed via Cox regression, which accounts for differences in follow-up times. RESULTS: Of the 1,359 subjects who had undergone hormonal GR in Finland from 1996 to 2019, 7.9% discontinued their established hormonal treatment during an average follow-up of 8.5 years. The risk for discontinuing hormonal GR was greater among later cohorts. The hazard ratio was 2.7 (95% confidence interval 1.1-6.1) among those who had accessed gender identity services from 2013 to 2019 compared with those who had come to contact from 1996 to 2005. Discontinuing also appeared to be emerging earlier among those who had entered the process in later years. CONCLUSIONS: The risk of discontinuing established medical GR has increased alongside the increase in the number of patients seeking and proceeding to medical GR. The threshold to initiate medical GR may have lowered, resulting in a greater risk of unbalanced treatment decisions. TRIAL REGISTRATION NUMBER (TRN): Not applicable (the paper does not present a clinical trial).

The Role of Sex and Gender in Transgender Bone and Other Musculoskeletal Health.

ABSTRACT: Musculoskeletal changes occur with gender-affirming hormonal therapy (GAHT) and gender-affirming surgery (GAS) used in the care of transgender adolescents and adults. Survey results have shown that orthopaedic surgeons desire to care for transgender individuals but express concern over a knowledge deficit. This article reviews the physiology and pathophysiology that may occur with GAHT and GAS. Transgender women have lower bone mineral density (BMD) prior to GAHT than cisgender men. Limited fracture data would suggest that transgender women >50 years of age have fracture rates similar to those of cisgender women. Transgender men have normal BMD prior to GAHT and are not at an increased risk for fracture compared with cisgender women. The use of puberty-blocking medications in the care of transgender youth does result in a decline in BMD, which returns to baseline with GAHT, but the effect of delaying puberty on maximal BMD and the lifetime fracture risk are unknown. At present, dual x-ray absorptiometry (DXA) is used to measure BMD and assess fracture risk. Attention should be paid to using the appropriate reference group in the interpretation of DXA for transgender individuals. Promote musculoskeletal health by ensuring appropriate calcium, vitamin D, weight-bearing activity, and a healthy lifestyle. Adherence to GAHT needs to be encouraged to avoid bone loss. Data with regard to therapy for osteoporosis in transgender patients have been lacking, but, at present, use of available therapies is expected to be effective. Information with regard to differences in other musculoskeletal health issues such as joint injuries has been lacking in transgender individuals.

Reproductive Considerations in the Transgender and Gender Diverse Population: A Review.

Many transgender and gender diverse (TGD) individuals will be considering gender-affirming treatments during their reproductive lifespan. These medically necessary treatments have a negative impact on reproductive potential. All TGD individuals should be counseled regarding fertility. Options for fertility preservation for individuals who have undergone puberty include mature oocyte, embryo, and sperm cryopreservation. In prepubertal individuals, ovarian tissue cryopreservation may be considered, but testicular tissue cryopreservation remains experimental only. While there have been advances in the technology and standardization of reproductive health care for this population, many gaps remain in our knowledge which require further research.

Sexual health in transgender and gender diverse people.

PURPOSE OF REVIEW: Sexual health and sexual function are critical to the wellbeing of cisgender, transgender, and gender diverse populations. To date, there has been only limited patient-focused evaluation of sexual function in transgender and gender diverse patients at several stages in their gender-affirming medical care. There remains a need to better understand the impact of gender affirming medical and surgical therapy on sexual health, and to develop evidence-based treatments to address sexual dysfunction when present. RECENT FINDINGS: The impact of gender-affirming hormone therapy on sexual health is complex and evolves over time on treatment. Despite high incidences of complications, major genital gender-affirming surgeries such as vulvovaginoplasty and penile implant placement after phalloplasty yield high patient satisfaction. While treatments to preserve or restore erections and to improve vaginal lubrication have been trialed based upon literature in cisgender populations, there remains minimal evidence to guide medical treatment of sexual dysfunction ranging from erectile dysfunction to dyspareunia. SUMMARY: There is a continued need for ongoing efforts to develop patient-reported outcome measures and rigorous investigation of sexual health preservation and restoration treatments in transgender and gender diverse populations.

Effect of testosterone therapy on breast tissue composition and mammographic breast density in trans masculine individuals.

BACKGROUND: The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs). METHODS: Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted. RESULTS: Longer duration of TT use was associated with increasing degrees of lobular atrophy (p < 0.001) but not fibrous content (p = 0.82). Every 6 months of TT was associated with decreasing amounts of epithelium (exp(ß) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(ß) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(ß) = 1.01, 95%CI 0.98,1.05, adj p = 0.39). The effect of TT on breast epithelium was attenuated in overweight/obese TMIs (exp(ß) = 0.98, 95% CI 0.95,1.01, adj p = 0.14). When comparing TT users versus non-users, TT users had 28% less epithelium (exp(ß) = 0.72, 95% CI 0.58,0.90, adj p = 0.003). There was no association between TT and radiologist's breast density assessment (p = 0.58) or LIBRA measurements (p > 0.05). CONCLUSIONS: TT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk.

Differences in Subjective Transition Outcomes Between Transgender and Gender-Diverse Individuals Who Completed Mandatory Psychiatric Assessment and Those Who Received Gender-Affirmative Medical Treatment in Croatia: A Cross-Sectional Online Survey.

The aim of this study was to evaluate different aspects of transition outcomes in groups of transgender and gender diverse (TGD) people based on their transition status. We divided the 70 TGD participants (19 individuals assigned male at birth and 51 assigned female at birth) into two groups: those who had completed their psychiatric and psychological evaluation (PPE), which is mandatory in Croatia, and those who had undergone gender-affirming medical treatment (GAMT) (both gender-affirming hormone treatment and gender-affirming surgery). The online survey included sociodemographic questions and a custom-designed nine-item scale. The items were specifically designed based on the DSM-5-TR criteria for gender dysphoria to assess subjectively perceived transition outcomes. We conducted a factor analysis of the scale followed by structural equation modeling for confirmation. Chi-squared and Mann-Whitney U tests were used to compare group differences. The following three-factor structure was confirmed: better functioning, reduced body dysphoria, and satisfaction with decision. A positive influence of better functioning on satisfaction with the decision was found. In addition, our results showed that TGD individuals who had undergone GAMT scored higher on better functioning than those who had just completed PPE. Both groups consistently scored high on satisfaction with the decision, with no statistically significant differences between them. Our findings suggest that TGD individuals view gender-affirming medical care as beneficial to their overall functioning.

Uterine changes in transgender men receiving testosterone therapy.

OBJECTIVES: Despite regular gender-affirming hormone therapy (GAHT), the presence of uterine bleeding can occur occasionally and cause profound discomfort. This study aimed to evaluate the histologic features and immunohistochemical expression of estrogen (ER), progesterone (PR), and androgen receptors (AR) in the endometrium and myometrium of transgender men receiving testosterone therapy and relate them to clinical and hormonal characteristics. DESIGN: Retrospective cross-sectional study. METHODS: Thirty-four transgender men undergoing gender-affirming surgery were included. Clinical, sociodemographic, and laboratory data as well as anatomopathological and immunohistochemical findings were evaluated. RESULTS: The participants' mean age was 42.35 (SD, 10.00) years, and body mass index was 28.16 (SD, 5.52) kg/m2. The mean GAHT duration before surgery was 5.36 (SD, 3.24) years. The mean testosterone levels were 814.98 (SD, 407.13) ng/dL, and estradiol levels were 55.22 (SD, 25.27) pg/mL. The endometrium was atrophic in 61.8%, proliferative in 17.6%, and secretory in 20.6%. Immunohistochemical receptor analysis revealed that endometrial epithelial cells expressed ER (90%) and PR (80%), with a lower expression of AR (30%). In stromal tissue, the median ER, PR, and AR expression was lower than that in the epithelium (60%, 70%, and 25%, respectively). The myometrium showed high expression of PR (90%) and ER (70%), with the highest expression of AR (65%) being localized to this region. CONCLUSIONS: In the present study, GAHT induced an atrophic condition of the endometrium in two-thirds of the transgender men, with a limited AR expression in the endometrial region. The present results suggest that testosterone-based GAHT for a mean of 5 years is safe in transgender men achieving amenorrhea.

[The treatment path of transgender and gender diverse (TGD) minors and the impact of medical-surgical treatments on their mental health.] / Il percorso di cura dei minori transgender e di genere diverso (TGD) e impatto dei trattamenti medico-chirurgici sulla loro salute mentale.

AIM: The Standards of Care (SOC-8) by the World Professional Association for Trans Health provide guidelines for the care of transgender and gender diverse individuals through safe and effective multi-professional interventions for physical and mental well-being. The aim of this work is to summarize the SOC-8 recommendations for childhood and adolescence, highlighting the importance of psychosocial assessment and available medical and surgical therapeutic options, and emphasizing the need for healthcare provider training. METHODS: The SOC-8 recommendations are based on scientific evidence and professional consensus from experts in transgender health, developing classification criteria and access to therapies, based on systematic literature reviews (PubMed and Embase). RESULTS: The SOC-8 underscores the importance of assessing and preserving gender identity, supporting prepubescent individuals from a psychosocial perspective, and ensuring adolescents access to medically and surgically conforming treatments according to local legislation. It is the responsibility of healthcare providers to understand and adapt international guidelines for an inclusive clinical practice of gender diversity. DISCUSSION AND CONCLUSIONS: Gender affirmation therapies in minors require comprehensive evaluation, parental involvement, and consideration of their cognitive and emotional maturity. Treatments should also focus on preserving fertility and accessing medicalized treatments which are beneficial to the well-being of transgender and gender diverse individuals.

Thrombotic risk associated with gender-affirming hormone therapy.

Transgender and gender-expansive (TG) people-those who identify with a gender other than their assigned sex at birth-frequently experience gender dysphoria, which is associated with negative health outcomes. One key strategy for improving gender dysphoria is the use of gender-affirming hormone therapy (GAHT): estrogen for feminization and testosterone for masculinization. Estrogen use in cisgender women is associated with well-established changes in hemostatic parameters, including increases in prothrombotic factors and decreases in inhibitors of coagulation. Cisgender women using estrogen have an increased risk of thrombosis. Studies of thrombosis risk associated with estrogen GAHT in TG people are less robust, with some studies limited by the use of hormones and hormone management strategies that are no longer recommended. However, TG women using estrogen appear to be at increased risk of both arterial and venous thrombosis, which may increase with longer time on estrogen. Testosterone use in both cisgender and transgender men is associated with increases in hemoglobin and hematocrit, which can lead to erythrocytosis and thus increased risk of thrombosis. The results of studies evaluating thrombosis risk in the setting of testosterone use are mixed. This review presents an overview of alterations in hemostatic parameters and thrombosis risk associated with use of exogenous estrogen and testosterone. Understanding what is known and unknown about thrombosis risk associated with use of these hormones is essential for hematologists who may be asked to evaluate TG people and provide guidance on management of those who may be at increased risk of thrombosis.

Variation in Time-to-Gender-Affirming Hormone Therapy in US Active Duty Service Members.

BACKGROUND: Beginning in July 2016, transgender service members in the US military were allowed to receive gender-affirming medical care, if so desired. OBJECTIVE: This study aimed to evaluate variation in time-to-hormone therapy initiation in active duty Service members after the receipt of a diagnosis indicative of gender dysphoria in the Military Health System. RESEARCH DESIGN: This retrospective cohort study included data from those enrolled in TRICARE Prime between July 2016 and December 2021 and extracted from the Military Health System Data Repository. PARTICIPANTS: A population-based sample of US Service members who had an encounter with a relevant International Classification of Diseases 9/10 diagnosis code. MEASURES: Time-to-gender-affirming hormone initiation after diagnosis receipt. RESULTS: A total of 2439 Service members were included (M age 24 y; 62% white, 16% Black; 12% Latine; 65% Junior Enlisted; 37% Army, 29% Navy, 25% Air Force, 7% Marine Corps; 46% first recorded administrative assigned gender marker female). Overall, 41% and 52% initiated gender-affirming hormone therapy within 1 and 3 years of diagnosis, respectively. In the generalized additive model, time-to-gender-affirming hormone initiation was longer for Service members with a first administrative assigned gender marker of male relative to female ( P <0.001), and Asian and Pacific Islander ( P =0.02) and Black ( P =0.047) relative to white Service members. In time-varying interactions, junior enlisted members had longer time-to-initiation, relative to senior enlisted members and junior officers, until about 2-years postinitial diagnosis. CONCLUSION: The significant variation and documented inequities indicate that institutional data-driven policy modifications are needed to ensure timely access for those desiring care.

Referrals For Gender-Affirming Hormone Treatment in Croatia's National Network for Transgender Healthcare.

A network of healthcare professionals specializing in transgender care was established in Croatia in 2011, and legal advancements were subsequently made in 2014. Both achievements made gender transition more transparent and thus more attainable in Croatia. This observational study was conducted to assess the number of transgender individuals initiating gender-affirming hormone treatment (GAHT) in Croatia and describes trends in age and sex assigned at birth. Between 2011 and 2022, a total of 111 transgender individuals initiated GAHT. Within the cohort, 52 were assigned male at birth (AMAB) and 59 were assigned female at birth (AFAB). The overall annual incidence rate of transgender individuals initiating GAHT was 0.52 per 100,000 age-adjusted individuals. There was a statistically significant increase (p < 0.01) in transgender individuals commencing GAHT before the COVID-19 pandemic. Furthermore, a rising trend toward masculinizing rather than feminizing treatment was identified (p < 0.05), particularly among younger transgender individuals. The COVID-19 pandemic disrupted these trends in 2020, except for the trend of initiating therapy at a younger age (p < 0.01). The annual incidence and age distribution trends of transgender individuals initiating GAHT in Croatia closely mirrored those in other European countries, with a higher prevalence of individuals assigned female at birth. The study underscores a significant rise in the number of individuals initiating gender-affirming hormone treatment, emphasizing the need for proper legal regulation and healthcare system response.

Clinicians in the Veterans Health Administration initiate gender-affirming hormone therapy in concordance with clinical guideline recommendations.

Background: Gender-affirming hormone therapy (GAHT) is a common medical intervention sought by transgender and gender diverse (TGD) individuals. Initiating GAHT in accordance with clinical guideline recommendations ensures delivery of high-quality care. However, no prior studies have examined how current GAHT initiation compares to recommended GAHT initiation. Objective: This study assessed guideline concordance around feminizing and masculinizing GAHT initiation in the Veterans Health Administration (VHA). Methods: The sample included 4,676 veterans with a gender identity disorder diagnosis who initiated feminizing (n=3,547) and masculinizing (n=1,129) GAHT between 2007 and 2018 in VHA. Demographics and health conditions on veterans receiving feminizing and masculinizing GAHT were assessed. Proportion of guideline concordant veterans on six VHA guidelines on feminizing and masculinizing GAHT initiation were determined. Results: Compared to veterans receiving masculinizing GAHT, a higher proportion of veterans receiving feminizing GAHT were older (≥60 years: 23.7% vs. 6.3%), White non-Hispanic (83.5% vs. 57.6%), and had a higher number of comorbidities (≥7: 14.0% vs. 10.6%). A higher proportion of veterans receiving masculinizing GAHT were Black non-Hispanic (21.5% vs. 3.5%), had posttraumatic stress disorder (43.0% vs. 33.9%) and positive military sexual trauma (33.5% vs.16.8%; all p-values<0.001) than veterans receiving feminizing GAHT. Among veterans who started feminizing GAHT with estrogen, 97.0% were guideline concordant due to no documentation of contraindication, including venous thromboembolism, breast cancer, stroke, or myocardial infarction. Among veterans who started spironolactone as part of feminizing GAHT, 98.1% were guideline concordant as they had no documentation of contraindication, including hyperkalemia or acute renal failure. Among veterans starting masculinizing GAHT, 90.1% were guideline concordant due to no documentation of contraindications, such as breast or prostate cancer. Hematocrit had been measured in 91.8% of veterans before initiating masculinizing GAHT, with 96.5% not having an elevated hematocrit (>50%) prior to starting masculinizing GAHT. Among veterans initiating feminizing and masculinizing GAHT, 91.2% had documentation of a gender identity disorder diagnosis prior to GAHT initiation. Conclusion: We observed high concordance between current GAHT initiation practices in VHA and guidelines, particularly for feminizing GAHT. Findings suggest that VHA clinicians are initiating feminizing GAHT in concordance with clinical guidelines. Future work should assess guideline concordance on monitoring and management of GAHT in VHA.

[Brain characteristics of transgender individuals and consequences of gender assignment treatment]. / Características cerebrales de las personas transexuales y consecuencias del tratamiento de asignación de género.

The differences between the male and female brain in cisgender individuals, those in whom there is no incongruence between the so-called biological sex and the perceived sex, are known. The genetic basis that underlies the differences observed in the brains of transgender individuals compared to cisgender individuals is also becoming known. In transgender individuals, there is a fundamental change in the connectivity of neurons in the body perception network, which may give rise to gender dysphoria. This knowledge allows for the characterization of the transgender condition and distinguishes it from transgender identities such as non-binary gender, gender fluidity, or genderqueer. Articles published assume, from the perspective of depathologization imposed by Gender Ideology, that these differences are due to a different sexual development. The societal acceptance of this perspective over the last two decades paved the way for medical interventions aimed at affirming the perceived gender, different from the genetic sex, through the continuous administration of cross-sex hormones and, in some cases, mutilating surgery. In adolescents and children, affirmation treatment of the perceived gender begins with puberty blockers, which have negative consequences for ossification and growth. The importance and irreversibility of these 'side effects' require the utmost rigor and complete information about them. Spanish law pushes the ideology to the maximum, infringing on the rights of transgender individuals. Medical ethics emphasize the necessity - the right - of a medical and psychological diagnosis, free from ideological approaches, before initiating what is being called treatment. This includes the right to information, prior to consent, about the positive and negative effects of hormonal administration. It also includes the right to the recognition of diversity among transgender individuals, especially the right to research that allows for treating the brain without altering the body. These rights must be recognized and demanded by the laws.

Treatment trajectories of gender incongruent Austrian youth seeking gender-affirming hormone therapy.

Objective: The aim of this study was to describe the treatment trajectories of Austrian children and adolescents with gender incongruence seeking gender-affirming medical care. Methods: Patients who presented with gender incongruence at the pediatric outpatient clinic for differences in sex development at a large university hospital in Austria from January 2008 to December 2022 were included in a retrospective chart review, and analyzed regarding referral numbers, patient characteristics, treatment trajectories, fertility preservation, and legal gender marker changes. Results: Of 310 eligible patients, 230 (74.2%) were assigned female at birth (AFAB), and 80 (25.8%) were assigned male at birth (AMAB). The number of referrals increased steeply from 2008 to 2018, whereafter it stabilized at around 50 per year. At the time of initial presentation, the median age of patients was 15.6 years (IQR 14.3-16.8). AMAB individuals tended to be younger (median 14.9 years, IQR 13.9-16.8) than AFAB individuals (median 15.8 years, IQR 14.4-16.8; p= 0.012). 207 (66,8%) completed the assessment process and were eligible for gender affirming medical treatment (GAMT). Of those, 89% (186/207) commenced gender affirming hormone therapy in the pediatric outpatient clinic (79/186 received GnRHa monotherapy, 91/186 GnRHa and sex steroids, and 16/186 sex steroid monotherapy). Of the 54 AMAB individuals receiving GAMT, 6 (11.1%) completed fertility preservation prior to therapy initiation. Only 1/132 AFAB adolescents receiving GAMT completed fertility preservation. Chest masculinization surgery was performed in 22 cases (16.7%), and breast augmentation in two cases (3.7%) between the ages of 16 and 18. Changes in legal gender marker were common, with 205 individuals (66.1%) having changed their legal gender marker. Conclusion: This is the first time that treatment trajectories, fertility preservation rates, and changes of legal gender marker have been described in Austrian adolescents with gender incongruence seeking GAMT. The majority received GAMT and changed their legal gender marker, while gender affirming surgery rates were low, and utilization of fertility preservation treatment options was rare.

Effects of gender-affirming hormone therapy on body fat: a retrospective case‒control study in Chinese transwomen.

BACKGROUND: There is insufficient research on how gender-affirming hormone therapy (GAHT) affects body fat modifications in transwomen from China. It is unclear whether hormone therapy affects the prevalence of obesity and blood lipid levels within this population. The current research aimed to assess how GAHT and treatment duration had an impact on the change in and redistribution of body fat in Chinese transwomen. METHODS: This study included 40 transwomen who had not received GAHT and 59 who had. Body fat, blood lipid, and blood glucose levels were measured. GAHT is mainly a pharmacologic (estrogen and anti-androgen) treatment. The study also stratified participants based on the duration of GAHT to assess its impact on body fat distribution. The duration of GAHT was within one year, one to two years, two to three years, or more than three years. RESULTS: After receiving GAHT, total body fat increased by 19.65%, and the percentage of body fat increased by 17.63%. The arm, corrected leg, and leg regions showed significant increases in fat content (+ 24.02%, + 50.69%, and + 41.47%, respectively) and percentage (+ 25.19%, + 34.90%, and + 30.39%, respectively). The total visceral fat content decreased (-37.49%). Based on the diagnostic standards for a body mass index ≥ 28 or total body fat percentage ≥ 25% or 30%, the chance of developing obesity did not change significantly. Blood glucose levels significantly increased (+ 12.31%). Total cholesterol levels (-10.45%) decreased significantly. Fat changes in those who received GAHT for one to two years were significantly different from those who did not receive GAHT. CONCLUSION: After receiving GAHT, total body fat and regional fat increased in Chinese transwomen, and the body fat distribution changed from masculine to feminine, especially during the first two years. However, neither the increase in total body fat percentage nor the decrease in visceral fat content didn't bring about significant changes in the incidence of obesity, nor did triglycerides or low-density lipoprotein-cholesterol.

Sexual Function in Post-surgical Transgender and Gender Diverse Individuals.

Surgical treatment for gender dysphoria consists of facial, chest, and genital surgery. Chest and genital gender affirmation surgeries alter the form and function of the native organs. This can have a profound impact on sexual function for transgender and gender- diverse individuals. In this article, the authors will discuss the impacts that chest and genital gender affirmation surgeries can have on sexual function.

Dermatologic needs of transgender and gender diverse youth: A retrospective cohort study.

Several dermatologic concerns are known to disproportionally affect transgender and gender-diverse (TGD) adults, but little is known about dermatologic conditions in TGD youth. This study assesses the prevalence of acne, androgenic alopecia, scarring from gender-affirming procedures, and eczema in pediatric TGD patients seen at Boston Children's Hospital between April 2021 and April 2022. The results demonstrate that, for TGD youth, the studied dermatologic concerns are common, referral rates to dermatology are low, and acne is significantly associated with testosterone use. Future studies should examine additional dermatologic concerns and barriers to accessing dermatologic care for this historically underserved population.

Gender-affirming hormone therapy and cardiovascular health in transgender adults.

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.

Association between serum estradiol and cardiovascular health among transgender adults using gender-affirming estrogen therapy.

Gender-affirming estrogen therapy (GAET) is commonly used for feminization in transgender and nonbinary (TNB) individuals, yet the optimal rate of change (ROC) in estradiol levels for cardiovascular health is unclear. We examined the association between serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and Web of Science were systematically searched (inception-April 2023) for original articles reporting serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Data extraction was completed in duplicate following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Stratified random effect meta-analyses using serum estradiol ROC (serum estradiolbaseline - serum estradiolfollow-up/study duration) was used to assess longitudinal studies (low, 0 < ROC ≤ 1 pg/mL/mo; moderate, 1 < ROC ≤ 3 pg/mL/mo; high, ROC ≥ 3 pg/mL/mo). Thirty-five studies (13 cross-sectional, 19 cohort, and 3 trials) were included. Two studies collectively reported 50 cardiovascular-related deaths, and four collectively reported 23 adverse cardiovascular events. Nineteen studies reporting cardiovascular risk factors were meta-analyzed by ROC stratum (low = 5; moderate = 6; high = 8), demonstrating an association between moderate [0.40, 95% confidence interval (CI): 0.22, 0.59 kg/m2, I2 = 28.2%] and high (0.46, 95% CI: 0.15, 0.78 kg/m2; I2 = 0.0%) serum estradiol ROC and increased body mass index. High (-6.67, 95% CI: -10.65, -2.68 mg/dL; I2 = 0.0%) serum estradiol ROC was associated with decreased low-density lipoproteins. Low (-7.05, 95% CI: -10.40, -3.70 mmHg; I2 = 0.0%) and moderate (-3.69, 95% CI: -4.93, -2.45 mmHg; I2 = 0.0%) serum estradiol ROCs were associated with decreases in systolic blood pressure. In TNB adults using GAET, serum estradiol ROC may influence cardiovascular risk factors, which may have implications for clinical cardiovascular outcomes.NEW & NOTEWORTHY In this systematic review and meta-analysis of 35 studies involving 7,745 participants, high rates of serum estradiol change were associated with small increases in body mass index. Moderate to high rates of change were associated with decreases in low-density lipoprotein. Low rates of change were associated with small decreases in systolic blood pressure. Rate of serum estradiol change in adults using gender-affirming estrogen therapy may influence cardiovascular risk factors, though further research is warranted.