Association between Serum Estradiol and Cardiovascular Health among Transgender Adults Using Gender-Affirming Estrogen Therapy.

INTRODUCTION: Gender-affirming estrogen therapy (GAET) is commonly used for feminization in transgender and non-binary (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. METHODS: 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 PRISMA guidelines. Stratified random effects meta-analyses using serum estradiol ROC (serum estradiolbaseline-serum estradiolfollow-up/study duration) was used to assess longitudinal studies (Low:0

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.

Sex- and Gender-Based Reporting in Antihypertensive Medication Literature Informing Hypertension Guidelines.

BACKGROUND: Hypertension is the leading modifiable cardiovascular risk factor with recognized sex- and gender-based differences. We assessed the incorporation of sex and gender reporting in the antihypertensive medication literature informing hypertension guidelines. METHODS AND RESULTS: Literature cited in the International Society of Hypertension (2020), European Society of Cardiology/European Society of Hypertension (2018), American College of Cardiology/American Heart Association (2017), Latin American Society of Hypertension (2017), Pan-African Society of Cardiology (2020), and Hypertension Canada (2020) guidelines was systematically reviewed. Observational studies, randomized controlled trials, and systematic reviews involving antihypertensive medications were included. Studies with participants of a single sex, guidelines, and commentaries were excluded. Data on study participation-to-prevalence ratio by sex, analysis of baseline demographics and study outcomes by sex, and stratification of adverse events by sex were extracted. Of 1659 unique citations, 331 studies met inclusion criteria. Of those, 81% reported the sex of participants, and 22% reported a male-to-female participation-to-prevalence ratio of 0.8 to 1.2. Three percent of studies stratified baseline characteristics by sex, and 20% considered sex during analysis through statistical adjustment or stratification. Although 32% of studies reported adverse events, only 0.6% stratified adverse events by sex. Most (58%) studies reporting sex/gender used sex and gender terms interchangeably. CONCLUSIONS: Incorporation of sex- and gender-based considerations in study population, analysis, or reporting of results and adverse events is not common in the antihypertensive medication literature informing international hypertension guidelines. Greater attention to sex- and gender-based factors in research is required to optimally inform management of hypertension.

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.