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.

A Holistic Framework for the Evaluation of Kidney Function in a Gender-Diverse Landscape.

The most commonly used equations to estimate glomerular filtration rate incorporate a binary male-female sex coefficient, which has important implications for the care of transgender, gender-diverse, and nonbinary (TGD) people. Whether "sex assigned at birth" or a binary "gender identity" is most appropriate for the computation of estimated glomerular filtration rate (eGFR) is unknown. Furthermore, the use of gender-affirming hormone therapy (GAHT) for the development of physical changes to align TGD people with their affirmed gender is increasingly common, and may result in changes in serum creatinine and cystatin C, the biomarkers commonly used to estimate glomerular filtration rate. The paucity of current literature evaluating chronic kidney disease (CKD) prevalence and outcomes in TGD individuals on GAHT makes it difficult to assess any effects of GAHT on kidney function. Whether alterations in serum creatinine reflect changes in glomerular filtration rate or simply changes in muscle mass is unknown. Therefore, we propose a holistic framework to evaluate kidney function in TGD people. The framework focuses on kidney disease prevalence, risk factors, sex hormones, eGFR, other kidney function assessment tools, and the mitigation of health inequities in TGD people.

Serum oestradiol levels and risk of adverse cardiovascular events associated with gender-affirming oestrogen therapy: a protocol for a systematic review and meta-analysis.

INTRODUCTION: The use of gender-affirming oestrogen therapy (GAOT) is an integral part of the gender-affirming transition process for transgender women (assigned male at birth who identify as women) and gender-diverse individuals. However, its use may present significant cardiovascular implications, which may be influenced by systemic oestradiol levels. Therefore, we aim to establish the association between serum oestradiol levels and incidence of adverse cardiovascular events in individuals using GAOT. METHODS AND ANALYSIS: We will conduct a systematic review addressing the association between serum oestradiol levels and risk of adverse cardiovascular events in individuals using GAOT. Our primary outcome is the incidence of adverse cardiovascular events, our secondary outcome is the incidence of cardiovascular-related mortality and our tertiary outcome is cardiovascular-related risk factors. Electronic databases (Cochrane Central Register of Controlled Trials, Embase, MEDLINE and Web of Science) will be searched from inception until September 2022. Two investigators will independently complete screening to determine appropriateness of inclusion. Extracted data will include information on serum sex hormone levels (oestradiol and testosterone), participants, GAOT (route of administration, formulations, dosages and duration of exposure), incidence of cardiovascular outcomes, study quality and risk of bias. Inter-reviewer reliability will be calculated at both phases. Data will be presented both descriptively and meta-analysed using a random effects model, if appropriate. Heterogeneity will be explored and meta-regressed if noted. ETHICS AND DISSEMINATION: Ethics approval is not needed. We will disseminate findings through international conferences, distributions to transgender and gender-diverse support organisations, decision-makers and key stakeholders. The final systematic review will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42021247717.

Gender-affirming estrogen therapy route of administration and cardiovascular risk: a systematic review and narrative synthesis.

Transgender women (individuals assigned male sex at birth who identify as women) and nonbinary and gender-diverse individuals receiving gender-affirming estrogen therapy (GAET) are at increased cardiovascular risk. Nonoral (i.e., patch, injectable) compared with oral estrogen exposure in cisgender women (individuals assigned female sex at birth who identify as women) may be associated with lower cardiovascular risk, though whether this applies to transgender women and/or gender-diverse individuals is unknown. We sought to determine the association between the route of estrogen exposure (nonoral compared with oral) and cardiovascular risk in transgender women and gender diverse individuals. Bibliographic databases (MEDLINE, Embase, PsycINFO) and supporting relevant literature were searched from inception to January 2022. Randomized controlled trials and observational studies reporting cardiovascular outcomes, such as all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors in individuals using nonoral compared with oral gender-affirming estrogen therapy were included. The search strategy identified 3,113 studies, 5 of which met inclusion criteria (3 prospective cohort studies, 1 retrospective cohort study, and 1 cross-sectional study; n = 259 participants, range of duration of exposure of 2 to 60 mo). One out of five studies reported on all-cause and cardiovascular mortality or adverse cardiovascular events. All five studies reported lipid levels [low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC)], whereas only two studies reported systolic blood pressure (SBP) and diastolic blood pressure (DBP). Limited studies have examined the effect of the route of GAET on all-cause cardiovascular mortality, morbidity, and risk factors. In addition, there is significant heterogeneity in studies examining the cardiovascular effects of GAET.NEW & NOTEWORTHY This study is the first to summarize the potential effect of nonoral versus oral gender-affirming estrogen therapy use on cardiovascular risk factors in transgender women or nonbinary or gender-diverse individuals. Heterogeneity of studies in reporting gender-affirming estrogen therapy formulation, dose, and duration of exposure limits quantification of the effect of gender-affirming estrogen therapy on all-cause and cardiovascular mortality, adverse cardiovascular events, and cardiovascular risk factors. This systematic review highlights the needs for large prospective cohort studies with appropriate stratification of gender-affirming estrogen therapy by dose, formulation, administration route, and sufficient follow-up and analyses to limit selection bias to optimize the cardiovascular care of transgender, nonbinary, and gender-diverse individuals.

Implications for management of ovarian cancer in a transgender man: Impact of androgens and androgen receptor status.

A 36-year-old transgender man (assigned female at birth) on exogenous testosterone therapy was found to have stage IIA ovarian endometrioid carcinoma, and underwent adjuvant chemotherapy. Diffuse androgen receptor expression in the tumor initiated a multidisciplinary discussion regarding the safety of continuing exogenous testosterone as gender-affirming hormone therapy.

Providing Care for Transgender Persons With Kidney Disease: A Narrative Review.

PURPOSE OF REVIEW: Nephrologists are increasingly providing care to transgender individuals with chronic kidney disease (CKD). However, they may lack familiarity with this patient population that faces unique challenges. The purpose of this review is to discuss the care of transgender persons and what nephrologists should be aware of when providing care to their transgender patients. SOURCES OF INFORMATION: Original research articles were identified from MEDLINE and Google Scholar using the search terms "transgender," "gender," "sex," "chronic kidney disease," "end stage kidney disease," "dialysis," "transplant," and "nephrology." METHODS: A focused review and critical appraisal of existing literature regarding the provision of care to transgender men and women with CKD including dialysis and transplant to identify specific issues related to gender-affirming therapy and chronic disease management in transgender persons. KEY FINDINGS: Transgender persons are at an increased risk of adverse outcomes compared with the cisgender population including mental health, cardiovascular disease, malignancy, sexually transmitted infections, and mortality. Individuals with CKD have a degree of hypogonadotropic hypogonadism and decreased levels of endogenous sex hormones; therefore, transgender persons with CKD may require reduced exogenous sex hormone dosing. Exogenous estradiol therapy increases the risk of venous thromboembolism and cardiovascular disease which may be further increased in CKD. Exogenous testosterone therapy increases the risk of polycythemia which should be closely monitored. The impact of gender-affirming hormone therapy on glomerular filtration rate (GFR) trajectory in CKD is unclear. Gender-affirming hormone therapy with testosterone, estradiol, and anti-androgen therapies changes body composition and lean body mass which influences creatinine generation and the performance for estimated glomerular filtration rate (eGFR) equations in transgender persons. Confirmation of eGFR with measured GFR is reasonable if an accurate knowledge of GFR is needed for clinical decision-making. LIMITATIONS: There are limited studies regarding the intersection of transgender persons and kidney disease and those that exist are mostly case reports. Randomized controlled trials and observational studies in nephrology do not routinely differentiate between cisgender and transgender participants. IMPLICATIONS: This review highlights important considerations for providing care to transgender persons with kidney disease. Additional research is needed to evaluate the performance of eGFR equations in transgender persons, the effects of gender-affirming hormone therapy, and the impact of being transgender on outcomes in persons with kidney disease.

MOTIF DE LA REVUE: Dans leur pratique, les néphrologues sont de plus en plus appelés à traiter des personnes transgenres atteintes d'insuffisance rénale chronique (IRC). Une population de patients qui fait face à des défis particuliers et avec laquelle les spécialistes ne sont pas toujours familiers. L'objectif de cette revue est de discuter des soins prodigués aux personnes transgenres et des enjeux auxquels les néphrologues qui soignent ces patients devraient être sensibilisés. SOURCES: Les articles de recherche originaux ont été répertoriés sur MEDLINE et Google Scholar à l'aide des termes transgender (transgenre), gender (genre), sex (sexe), chronic kidney disease (insuffisance rénale chronique), end stage kidney disease (insuffisance rénale terminale), dialysis (dialyse), transplant (transplantation) et nephrology (néphrologie). MÉTHODOLOGIE: On a procédé à un examen ciblé et une évaluation critique de la documentation portant sur les soins aux personnes transgenres atteintes d'IRC, notamment la dialyse et la transplantation, afin de cerner les enjeux liés spécifiquement aux thérapies d'affirmation du genre et à la prise en charge de la néphropathie chronique chez les personnes transgenres. PRINCIPAUX RÉSULTATS: Les personnes transgenres courent un risque accru d'événements défavorables comparativement à la population cisgenre, notamment en matière de santé mentale, de maladies cardiovasculaires, de tumeurs malignes, d'infections transmissibles sexuellement et de mortalité. Les individus atteints d'IRC présentent un certain degré d'hypogonadisme hypogonadotrope et des taux réduits d'hormones sexuelles endogènes; les personnes transgenres atteintes d'IRC pourraient ainsi nécessiter un dosage réduit d'hormones sexuelles exogènes. L'estradiol exogène augmente le risque de thrombo-embolie veineuse et de maladies cardiovasculaires, un risque pouvant être augmenté davantage en contexte d'IRC. La testostérone exogène augmente le risque de polycythémie et doit être surveillée étroitement. L'impact de l'hormonothérapie d'affirmation du genre sur la trajectoire du débit de filtration glomérulaire (DFG) en IRC est encore mal connu. L'hormonothérapie d'affirmation du genre avec testostérone, estradiol et anti-androgène altère la composition corporelle et la masse maigre, ce qui influe sur la production de créatinine et la performance des équations calculant le DFG estimé (DFGe) chez les personnes transgenres. La confirmation du DFGe à l'aide du DFG mesuré est raisonnable si connaître la valeur précise du DFG est nécessaire pour la prise de décision clinique. LIMITES: Peu d'études se sont penchées sur l'intersection des personnes transgenres et de la néphropathie, et les études existantes consistent principalement en des rapports de cas. Les essais contrôlés randomisés et les études observationnelles en néphrologie ne font pas systématiquement de distinction entre les participants cisgenres et transgenres. CONCLUSION: Cette revue met en lumière des considérations importantes pour la prise en charge des personnes transgenres atteintes de néphropathies. D'autres recherches sont nécessaires pour évaluer la performance des équations calculant le DFGe, les effets de l'hormonothérapie d'affirmation du genre et l'incidence d'être transgenre sur les résultats des personnes atteintes de néphropathies.

Breast cancer in transgender female-to-male individuals: A case report of androgen receptor-positive breast cancer.

Highlight the challenges associated with managing breast cancer in female-to-male (FtM) transgender individuals. This is a rare entity, requiring nuanced decision-making regarding surgery as well as adjuvant therapies given the unique hormonal environment seen in individuals taking exogenous androgen as part of their gender identity. Contemporary case report derived from our clinical experience. Discussion focuses on a brief summation of all known cases of female-to-male breast cancer in FtM individuals described in the literature. A 48-year-old FtM transgender individual on exogenous testosterone for 19 years with stage IIA (pT1cN1M0), ER+(8/8), PR+(8/8), Androgen Receptor(AR)+(5%-8%), Her-2-negative invasive ductal carcinoma of the breast. Due to AR positivity in tumor, cessation of testosterone was chosen after careful consideration of potential ramifications from both a cancer treatment as well as gender identity standpoint. Endocrinology consultation reassured the patient that identity affirming changes of facial hair growth and voice depth would persist after cessation of testosterone. Patient did not wish to undergo chemotherapy and as such was treated with combination of radiation to the axilla, adjuvant Anastrozole and testosterone cessation. Although breast cancer is rare in FtM transgender individuals, it can occur. Many FtM individuals take exogenous testosterone. It is important to test the tumor for the androgen receptor as this may have important implications for both gender identity and treatment. Additionally, the mastectomy commonly performed for "top" surgery in this population is not adequate for oncologic control by itself and at present there is no guidance regarding postsurgical screening in this population, especially in those individuals with a strong family history of breast cancer.

Early COPD Diagnosis in Family Medicine Practice: How to Implement Spirometry?

Introduction. COPD is often diagnosed at an advanced stage because symptoms go unrecognized. Furthermore, spirometry is often not done. Methods. Study was conducted in diverse family medicine practice settings. Patients were targeted if respiratory symptoms were present. Patients had a spirometry to confirm the presence of airflow obstruction and COPD diagnosis. An evaluation of the process was done to better understand facilitating/limiting factors to the implementation of a primary care based spirometry program. Results. 12 of 19 primary care offices participated. 196 of 246 (80%) patients targeted based on the presence of smoking and respiratory symptoms did not have COPD; 18 (7%) and 32 (13%) had COPD, respectively, GOLD I and ≥II. There was no difference in the type and number of respiratory symptoms between non-COPD and COPD patients. Most of the clinics did not have access to a trained healthcare professional to accomplish spirometry. They agreed that giving access to a trained healthcare professional was the easiest and most reliable way of doing spirometry. Conclusion. Spirometry, a simple test, is recommended in guidelines to make the diagnosis of COPD. The lack of allocated time and training of healthcare professionals makes its implementation challenging in family medicine practices.

Multiple adult xanthogranuloma: case report and literature review.

BACKGROUND: Non-Langerhans cell histiocytoses form a heterogeneous group defined by the proliferation of cells with macrophage characteristics. Diagnosis is easy in typical cases but becomes more complex in unusual forms. CASE REPORT: We report the case of a 53-year-old patient who presented multiple brown-to-yellowish papules and nodules of the trunk, neck, and head evolving for 6 months. No visceral involvement was found. Histopathological examination revealed histiocytic proliferation with features of secondary xanthomization with the presence of giant foamy multinucleated Touton cells. One year later, all lesions cleared spontaneously. Based on the clinical presentation and evolution and on the immunohistologic data, we retain the diagnosis of adult xanthogranuloma (AXG) in a diffuse shape. DISCUSSION: Multiple AXG is a rare entity (15 cases reported since 1963) with a stereotypic presentation. It is important to recognize because of its good prognosis and the absence of visceral involvement therefore requiring no investigations or aggressive treatments. This case is interesting because of the complete and spontaneous healing of all the lesions within 20 months.