Effectiveness and Safety of Different Estradiol Regimens in Transgender Females: A Randomized Controlled Trial.

Background: A goal of gender-affirming hormone therapy (GAHT) for transgender women is to use estradiol to suppress endogenous production of testosterone. However, the effects of different estradiol regimens and route of administration on testosterone suppression is unknown. This is the first open-label randomized trial comparing different GAHT regimens for optimal estradiol route and dosing. Objective: To evaluate 1 month and 6 months testosterone suppression <50 ng/dL with pulsed (once- or twice-daily sublingual 17-beta estradiol) and continuous (transdermal 17-beta estradiol) GAHT. Methods: This study was conducted at an outpatient adult transgender clinic. Thirty-nine transgender women undergoing initiation of GAHT were randomly assigned to receive either once-daily sublingual, twice-daily sublingual, or transdermal 17-beta estradiol. All participants received spironolactone as an antiandrogen. Doses were titrated at monthly intervals to achieve total testosterone suppression <50 ng/dL. Results: Transdermal 17-beta estradiol resulted in more rapid suppression of total testosterone, lower estrone levels, with no differences in estradiol levels when compared to once-daily and twice-daily sublingual estradiol. Moreover, there was no difference in the mean estradiol dose between the once-daily and twice-daily sublingual 17-beta estradiol group. Conclusion: Continuous exposure with transdermal 17-beta estradiol suppressed testosterone production more effectively and with lower overall estradiol doses relative to once or twice daily sublingual estradiol. Most transgender women achieved cisgender women testosterone levels within 2 months on 1 or 2 0.1 mg/24 hours estradiol patches. Given no difference between once- or twice-daily sublingual estradiol, pulsed 17-beta estradiol likely provides no benefit for testosterone suppression.

Transgender Women With Suppressed Testosterone Display Lower Burden of Coronary Disease Than Matched Cisgender Men.

Context: Cardiovascular disease (CVD) in transgender women (TW) may be affected by gender-affirming hormone therapy (GAHT) and HIV, but few data compare TW on contemporary GAHT to well-matched controls. Objective: We compared CVD burden and biomarker profiles between TW and matched cisgender men (CM). Methods: Adult TW on GAHT (n = 29) were recruited for a cross-sectional study (2018-2020). CM (n = 48) from the former Multicenter AIDS Cohort Study were matched 2:1 to TW on HIV serostatus, age ±5 years, race/ethnicity, BMI category and antiretroviral therapy (ART) type. Cardiac parameters were measured by CT and coronary atherosclerosis by coronary CT angiography; sex hormone and biomarker concentrations were measured centrally from stored samples. Results: Overall, median age was 53 years and BMI 29 kg/m2; 69% were non-white. All participants with HIV (71%) had viral suppression on ART. Only 31% of TW had testosterone suppression (<50 ng/dL, TW-S). Traditional CVD risk factors were similar between groups, except that TW-S had higher BMI than TW with non-suppressed testosterone (TW-T). TW-S had no evidence of non-calcified coronary plaque or advanced coronary stenosis, whereas TW-T and CM had similar burden. TW had lower prevalence of any coronary plaque, calcified plaque and mixed plaque than CM, regardless of testosterone concentrations and HIV serostatus. Estradiol but not testosterone concentrations moderately and negatively correlated with the presence of coronary plaque and stenosis. Small sample size limited statistical power. Conclusion: Older TW with suppressed total testosterone on GAHT had no CT evidence of non-calcified coronary plaque or advanced coronary stenosis. Longitudinal studies to understand relationships between GAHT and CVD risk in TW are needed.

Evaluation of Sexual Function of Transgender Individuals.

PURPOSE: The current study sought to evaluate the sexual function of transgender men and women and to identify associated factors. METHODS: Trans individuals who were outpatients at our gender incongruence (GI) center for follow-up of gender-affirming hormone therapy with age ranging 27 to 50 years were invited to participate in this cross-sectional study. Clinical data were collected from the medical records. Two scales, the Female Sexual Function Index (FSFI) and the Male Sexual Function Index (MSFI), were administered to all females (n = 50) and all males (n = 58). Each participant also responded to a semi-structured questionnaire that assessed feelings regarding being transgender and satisfaction with sexual life. RESULTS: Relative to trans women, trans men had a higher total FSFI score, and higher scores in the FSFI domains of arousal, lubrication, orgasm, and satisfaction (all p < 0.01), and in the total MSFI score, and higher scores in the MFSI domains of arousal, erection, orgasm, and satisfaction (all p < 0.01). A separate semi-structured evaluation indicated that more than half of the trans men and almost half of the trans women were satisfied or very satisfied with their sexual life. CONCLUSIONS: The total scores from the FSFI and MSFI indicated a high risk of sexual dysfunction in trans men and especially, in trans women. However, the semi-structured evaluation showed that more than half of the trans men and almost half of the trans women were satisfied with their sexual life.

Effects of gender-affirming hormone therapy on gray matter density, microstructure and monoamine oxidase A levels in transgender subjects.

MAO-A catalyzes the oxidative degradation of monoamines and is thus implicated in sex-specific neuroplastic processes that influence gray matter (GM) density (GMD) and microstructure (GMM). Given the exact monitoring of plasma hormone levels and sex steroid intake, transgender individuals undergoing gender-affirming hormone therapy (GHT) represent a valuable cohort to potentially investigate sex steroid-induced changes of GM and concomitant MAO-A density. Here, we investigated the effects of GHT over a median time period of 4.5 months on GMD and GMM as well as MAO-A distribution volume. To this end, 20 cisgender women, 11 cisgender men, 20 transgender women and 10 transgender men underwent two MRI scans in a longitudinal design. PET scans using [11C]harmine were performed before each MRI session in a subset of 35 individuals. GM changes determined by diffusion weighted imaging (DWI) metrics for GMM and voxel based morphometry (VBM) for GMD were estimated using repeated measures ANOVA. Regions showing significant changes of both GMM and GMD were used for the subsequent analysis of MAO-A density. These involved the fusiform gyrus, rolandic operculum, inferior occipital cortex, middle and anterior cingulum, bilateral insula, cerebellum and the lingual gyrus (post-hoc tests: pFWE+Bonferroni < 0.025). In terms of MAO-A distribution volume, no significant effects were found. Additionally, the sexual desire inventory (SDI) was applied to assess GHT-induced changes in sexual desire, showing an increase of SDI scores among transgender men. Changes in the GMD of the bilateral insula showed a moderate correlation to SDI scores (rho = - 0.62, pBonferroni = 0.047). The present results are indicative of a reliable influence of gender-affirming hormone therapy on 1) GMD and GMM following an interregional pattern and 2) sexual desire specifically among transgender men.

One person, many changes: a socioecological qualitative analysis of the experiences of transfeminine individuals undergoing feminising gender-affirming hormone therapy.

Gender-affirming hormone therapy (GAHT) comes with many physical, psychological, and social changes that are often considered in isolation. This research uses a socioecological lens with a sample of 15 Australian transfeminine individuals to investigate the changes experienced during GAHT. Semi-structured interviews were conducted in 2022, with verbatim transcripts analysed using deductive thematic analysis with Bronfenbrenner's Socioecological Model (SEM) as a framework. Analyses revealed two themes intersecting multiple levels of the SEM. Theme 1 contained two sub-themes and broadly encapsulated how interactions with others influenced GAHT experiences. Sub-theme 1 spoke to how stigma creates positive or negative experiences (through the macrosystem, the exosystem, and proximal processes), while sub-theme 2 described how GAHT causes internal changes that promoted stronger interpersonal relationships (person and proximal processes). Theme 2 described how changes occurred over time, with some changes being temporary, and others being delayed (person and time). These themes highlight the interconnected nature of the physical, psychological, and social changes and experiences that can occur during GAHT. Best-practice care for trans people undergoing GAHT needs to be multi-faceted and holistic in order to embed support across different SEM components.

Biochemical liver damage during gender affirming therapy in trans adults assigned female at birth: a meta-analysis.

PURPOSE: To assess the effects of testosterone (T)-based gender affirming hormone therapy (GAHT) on liver blood tests (LBTs) in assigned female at birth adults, using a meta-analytic approach. METHODS: Prospective and retrospective studies were selected that reported the prevalence of biochemical liver damage (BLD) and LBTs changes during T therapy. Data collected included pre-and-during therapy alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), gamma-glutamyl-transferase (GGT), and alkaline phosphatase (ALP) mean concentration values. RESULTS: The prevalence of BLD in 14 studies on 1698 subjects was 1% (95% CI 0.00-3.00; I2 = 14.1%; p = 0.82). In 17 studies on 2758 subjects, GAHT was associated with a statistically (but not clinically) significant increase in AST, GGT and ALP at 12 months and ALT at 3-7 (MD: 1.19 IU/l; 95% CI 0.31, 2.08; I2: 0%), at 12 (MD: 2.31 IU/l; 95% CI 1.41, 3.21; I2: 29%), but with no more significant increase at 24 months (MD: 1.71 IU/l; 95% CI -0.02, 3.44; I2: 0%). CONCLUSIONS: Analysis of aggregate estimates confirms a low risk of BLD and abnormalities in LBTs, transient in most cases, during T-based GAHT, thus suggesting a limited need for careful liver monitoring in AFAB people.

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.

Resolution of metabolic dysfunction-associated steatohepatitis with estradiol in a transgender female: A case report.

A 16-year-old trans female patient presented to our Gender Health Program for gender-affirming care. Her intake evaluation revealed signs of hepatocellular injury and fibrosis concerning for metabolic dysfunction-associated steatohepatitis (MASH) and she was referred to a Pediatric Hepatologist. Subsequent delays in initiating hormone therapy caused a decline in her mental health, and she began experiencing suicidal ideations. Gender-affirming hormone therapy has been shown to significantly reduce depressive symptoms and suicidal ideations in transgender and gender diverse youth, and studies in animal models suggest improvement in hepatic steatosis in response to estrogen. A multidisciplinary meeting with Gender Health, Psychiatry, and Hepatology appropriately weighed the benefits of life-saving hormone therapy and the possibility of an improvement in her comorbid liver condition with the risk of further liver damage from estrogen therapy. The teams and the patient agreed to start estradiol with subsequent resolution of laboratory and radiographic evidence of MASH.

The association of gender-affirming hormone therapy duration and body mass index on bone mineral density in gender diverse adults.

Introduction: Feminizing and masculinizing gender-affirming hormone therapy (fGAHT, mGAHT) results in bone mineral density (BMD) maintenance or improvement over time in transgender and gender diverse (TGD) adults. Mostly European TGD studies have explored GAHT's impact on BMD, but the association of BMI and BMD in TGD adults deserves further study. Objective: To determine whether GAHT duration or BMI are associated with BMD and Z-scores among TGD young adults. Methods: Cross-sectional study of nonsmoking TGD adults aged 18-40 years without prior gonadectomy or gonadotropin-releasing hormone agonist (GnRHa) therapy taking GAHT for > 1 year. BMD and Z-scores were collected from dual-energy x-ray absorptiometry. Associations between femoral neck, total hip, and lumbar spine BMDs and Z-scores and the predictors, GAHT duration and BMI, were estimated using linear regression. Results: Among 15 fGAHT and 15 mGAHT, mean BMIs were 27.6 +/- standard deviation (SD) 6.4 kg/m2 and 25.3 +/- 5.9 kg/m2, respectively. Both groups had mean BMDs and Z-scores within expected male and female reference ranges at all three sites. Higher BMI among mGAHT was associated with higher femoral neck and total hip BMDs (femoral neck: ß = 0.019 +/- standard error [SE] 0.007 g/cm2, total hip: ß = 0.017 +/- 0.006 g/cm2; both p < 0.05) and Z-scores using male and female references. GAHT duration was not associated with BMDs or Z-scores for either group. Conclusions: Z-scores in young, nonsmoking TGD adults taking GAHT for > 1 year, without prior gonadectomy or GnRHa, and with mean BMIs in the overweight range, were reassuringly within the expected ranges for age based on male and female references. Higher BMI, but not longer GAHT duration, was associated with higher femoral neck and total hip BMDs and Z-scores among mGAHT. Larger, prospective studies are needed to understand how body composition changes, normal or low BMIs, and gonadectomy affect bone density in TGD adults.

Changes in Blood Lipids Following Initiation of Gender Affirming Hormone Therapy: A Systematic Review and Meta-Analysis.

Aim: The aim of this study was to conduct a systematic review and meta-analysis of changes in low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides following initiation of feminizing or masculinizing gender affirming hormone therapy (GAHT). Methods: A search of Ovid MEDLINE, Embase, Web of Science, SCOPUS, and CINAHL databases identified potentially relevant articles published from 1990 through 2024. Both observational and randomized trials of adults receiving feminizing or masculinizing GAHT with baseline and follow-up measures were included. Articles were reviewed for eligibility using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines. The risk of bias in each study was quantified using the NHLBI Study Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group. Random effects models were used to compute the before-and-after meta-differences in mean values for each parameter along with the I2 statistic to assess heterogeneity of results. Results: Thirty-five studies met the criteria for inclusion in the meta-analysis. Masculinizing GAHT was associated with significant changes in serum lipids from baseline up through the 60-month timepoint with meta-difference of means (95% CI) estimates of 26.2mg/dL (23.3,29.0) for LDL-C, 26.1mg/dL (22.8,29.4) for total cholesterol, 30.7mg/dL (6.9,54.6) for triglycerides and -9.4mg/dL (-12.1, -6.7) for HDL-C. Studies evaluating the effects of feminizing GAHT on balance demonstrated no notable changes in HDL-C or triglycerides while the results for LDL-C and total cholesterol were inconsistent. Heterogeneity of results ranged from minimal (I2 = 0%) to substantial (I2 = 90%). Conclusions: While the results for transfeminine individuals on GAHT appear somewhat reassuring, transmasculine patients receiving testosterone may benefit from closer monitoring of lipid profiles.

Hematospermia in a Transgender Woman with Evidence for Endometrial Tissue in the Prostate.

Background/Objective: The frequency of hematospermia in transgender women is unknown. This report aimed to describe the development of hematospermia in a transgender woman. Case Report: A 35-year-old transgender woman treated with estradiol valerate and leuprolide presented with painless rust-tinged ejaculate, urethral bleeding after ejaculation, and intermittent hematuria. Her medical history included gastroesophageal reflux disease, internal hemorrhoids, and attention deficit hyperactivity disorder with negative tobacco smoking and urologic history. Additional medications included emtricitabine-tenofovir disoproxil fumarate and fexofenadine. Physical examination did not reveal constitutional or genitourinary abnormalities. Urinalysis and culture disclosed rare white blood cells with gram-variable bacilli. The chlamydia, gonorrhea, and human immunodeficiency virus test results were negative. Abdominal computed tomography did not reveal bladder or prostate cancer, calcifications, inflammation, or cysts. She continued to have symptoms after this initial workup. One year after the initial symptom onset, transrectal ultrasound disclosed a 1.7-cm midline posterior prostatic cyst with hemorrhagic products, later revealed by magnetic resonance imaging as communicating with the left seminal vesicle. Two ultrasound-guided transperineal biopsy samples revealed benign prostatic tissue with a small focus of Müllerian or endometrial-type tissue, evidenced by immunopositivity for paired-box gene 8 and estrogen receptor in epithelium and cluster of differentiation 10 immunopositivity in stroma. After medical consultation, the patient underwent prostatic cyst aspiration, resection of the transurethral ejaculatory ducts, and orchiectomy. She did not experience any complications after these procedures. Discussion: The etiology of hematospermia may be idiopathic, iatrogenic, anatomic, or pathologic. Conclusion: Occult endometriosis or ectopic Müllerian epithelial tissue growth may occur in transgender women taking feminizing gender-affirming hormone therapy.

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.

Patient Characteristics Associated with Receiving Gender-Affirming Hormone Therapy in the Veterans Health Administration.

Purpose: This study aimed to examine patient characteristics associated with receipt of gender-affirming hormone therapy in the Veterans Health Administration (VHA). Methods: This cross-sectional study included a national cohort of 9555 transgender and gender diverse (TGD) patients with TGD-related diagnosis codes who received care in the VHA from 2006 to 2018. Logistic regression models were used to determine the association of health conditions and documented social stressors with receipt of gender affirming hormone therapy. Results: Of the 9555 TGD patients, 57.4% received gender-affirming hormone therapy in the VHA. In fully adjusted models, patients who had following characteristics were less likely to obtain gender-affirming hormones in the VHA: Black, non-Hispanic versus white (adjusted odds ratio [aOR]: 0.61; 95% confidence interval [CI]: 0.52-0.72), living in the Northeast versus the West (aOR: 0.72; 95% CI: 0.62-0.84), a documented drug use disorder (aOR: 0.56; 95% CI: 0.47-0.68), ≥3 versus no comorbidities (aOR: 0.44; 95% CI: 0.34-0.57), and ≥3 versus no social stressors (aOR: 0.42; 95% CI: 0.30-0.58; all p<0.001). Younger patients aged 21-29 years were almost 3 times more likely to receive gender affirming hormone therapy in the VHA than those aged ≥60 (aOR: 2.98; 95% CI: 2.55-3.47; p<0.001). Conclusion: TGD individuals who were older, Black, non-Hispanic, and had more comorbidities and documented social stressors were less likely to receive gender-affirming hormone therapy in the VHA. Further understanding of patient preferences in addition to clinician- and site-level determinants that may impact access to gender-affirming hormone therapy for TGD individuals in the VHA is needed.

The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels.

OBJECTIVE: Feminizing gender-affirming hormone therapy is the mainstay of treatment for many transgender and gender diverse people. Injectable estradiol preparations are recommended by the World Professional Association for Transgender Health Standards of Care 8 and the Endocrine Society guidelines. Many patients prefer this route of administration, but few studies have rigorously assessed optimal dosing or route. METHODS: We performed a scoping review of the available data on estradiol levels achieved with various dosages of estradiol injections in transgender and gender diverse adults on feminizing gender-affirming hormone therapy. We also report on testosterone suppression, route (ie, subcutaneous vs intramuscular), and type of injectable estradiol ester as well as timing of blood draw relative to the most recent dose, where available. RESULTS: The data we reviewed suggest that the current guidelines, which recommend starting doses 2 to 10 mg weekly or 5 to 30 mg every 2 weeks of estradiol cypionate or valerate, are too high and likely lead to patients having supraphysiologic levels across much of their injection cycle. CONCLUSIONS: The optimal starting dose for injectable estradiol remains unclear and whether it should differ for cypionate and valerate. Based on the data available, we suggest that clinicians start injectable estradiol cypionate or valerate via subcutaneous or intramuscular injections at a dose ≤5 mg weekly and then titrate accordingly to keep levels within guideline-recommended range. Future studies should assess timing of injections and subsequent levels more precisely across the injection cycle and between esters.

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.

Preservación de la fertilidad en personas transgénero del espectro masculino. Revisión narrativa de la literatura / Fertility preservation in transmasculine people: Narrative review

La terapia hormonal de afirmación de género con testosterona (GAHT, por sus siglas en inglés) permite, a las personas transgénero del espectro masculino, modificar las características sexuales secundarias del sexo asignado al nacer, aliviando así los síntomas de la disforia de género durante el proceso denominado transición. Sin embargo, se debe tener presente que se desconoce, en la actualidad, el efecto de la GAHT sobre la fertilidad a largo plazo, y el potencial efecto gonadotóxico de la misma. La demanda de un correcto asesoramiento reproductivo y la opción de realizar técnicas de preservación de la fertilidad (PF) han aumentado de forma exponencial en los últimos años, comportando cambios profundos en el manejo clínico de estas personas. En este artículo se realiza una revisión bibliográfica sobre el efecto de la GAHT a nivel reproductivo y en la fertilidad, junto con las técnicas de PF disponibles en este colectivo, principalmente la vitrificación de ovocitos. Además, realizamos un análisis de los resultados reproductivos publicados hasta la fecha tras el uso de técnicas de preservación, y exponemos los últimos avances de laboratorio en relación con la criopreservación de tejido ovárico y la maduración in vitro de ovocitos, junto con las opciones de futuro en población transgénero del espectro masculino.(AU)

Gender affirming hormone therapy (GAHT) in transmasculine people (individuals who identify as men or on the masculine spectrum and were assigned female sex at birth) makes it possible to modify the secondary sexual characteristics of the sex assigned at birth, thus alleviating the symptoms of gender dysphoria, during the process called transition. However, it is necessary to highlight that the effect of GAHT on long-term fertility and its potential gonadotoxic effects are currently unknown. Knowledge of the effects of testosterone on fertility and reproduction has increased recently, whilst the request for comprehensive reproductive counselling and the option of performing fertility preservation (FP) techniques have increased exponentially in recent years, leading to profound changes in the clinical management of this population. In this review, we analyzed all the information published regarding the effect of GAHT on reproduction and the FP techniques available in this group, mainly oocyte vitrification. In addition, we carry out an exhaustive analysis of the reproductive results published to date after the use of preservation techniques and present the latest laboratory advances concerning ovarian tissue cryopreservation and in vitro oocyte maturation, together with future options in the transmasculine people.(AU)

Musculoskeletal and cardiovascular considerations for transgender athletes.

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.

Genital Surgery Outcomes Using an Individualized Algorithm for Hormone Management in Transfeminine Individuals.

CONTEXT: Transgender and gender diverse (TGD) individuals have greater access to genital surgery (GS) with improved insurance coverage and access to trained surgeons and interdisciplinary gender affirming providers. OBJECTIVE: To determine perioperative medical and behavioral health outcomes in transfeminine (TF) individuals undergoing GS with use of a specific gender-affirming hormone therapy (GAHT) algorithm based on individualized risk factor assessment. DESIGN: Retrospective observational cohort study from 2017-2022. Pre- and post-operative data collected included clinical and biochemical assessment, GAHT regimens, validated behavioral health measures, and post-operative complications. SETTING: Single-center tertiary referral center. PATIENTS: 183 TF individuals, grouped into estradiol continued (Group 1) vs estradiol temporarily discontinued for 2-6 weeks preoperatively (Group 2). MAIN OUTCOME MEASURE(S): Venous thromboembolism (VTE) incidence, non-VTE postoperative complication incidence, and change in behavioral health assessments. RESULTS: The majority of individuals continued estradiol perioperatively [Group 1; 138 (75.4%)]. Individuals who temporarily held estradiol preoperatively [Group 2; 45 (24.6%)] were statistically older (p < 0.01), had higher incidence of cardiometabolic comorbidities (p < 0.01), and higher Caprini scores (p < 0.01). Group 1 was statistically more likely to use oral estradiol (p < 0.01). One episode (0.05%) of VTE occurred (Group 1). There was no significant difference in postoperative complications or behavioral health measures between groups. CONCLUSION: An individualized algorithm for preoperative hormone management for TF GS resulted in perioperative continuation of GAHT for the majority of individuals without significantly increasing the risk for post-operative surgical complications while maintaining stable behavioral health measures perioperatively.

The effects of gender-affirming hormone therapy and mastectomy on psychopathology, body image, and quality of life in adults with gender dysphoria who were assigned female at birth.

PURPOSE: Individuals with gender dysphoria (GD) may request hormone therapy and various surgical operations to change their physical characteristics. The present study aimed to investigate the effects of two treatments, mastectomy and gender-affirming hormone therapy (GAHT), on adults with GD who were assigned female at birth (GD AFAB). METHODS: In this cross-sectional study, we gathered data from a total of 269 individuals in three groups: (a) untreated group (n = 121), (b) GAHT group (n = 84) who had been receiving treatment for at least 6 months, and (c) GAHT-MAST group (n = 64) who had been using GAHT for at least 6 months and had undergone mastectomy at least 3 months prior. All participants were asked to complete the Symptom Checklist-90-Revised (SCL-90-R), the Body Uneasiness Test (BUT), and the World Health Organization's Quality of Life Questionnaire- Brief Form, Turkish Version (WHOQOL-BREF-Tr). RESULTS: We found that individuals in the untreated group had higher psychopathological symptoms and body uneasiness scores, and lower quality of life scores compared to both GAHT and GAHT-MAST groups. There was no difference in psychopathology between the GAHT-MAST group and the GAHT group, but body uneasiness scores were lower, and quality of life scores were higher in the GAHT-MAST group. CONCLUSION: Our study suggests that individuals receiving GAHT improved mental health, body satisfaction, and overall quality of life. Combining mastectomy with GAHT may further enhance these benefits.

Bone Density in Transgender Youth on Gender-Affirming Hormone Therapy.

Some transgender youth are treated with gonadotropin-releasing hormone agonists (GnRHa) followed by testosterone or estradiol, which may impact bone mineral density (BMD). This cross-sectional study of transgender youth (n = 56, aged 10.4-19.8 years, 53% assigned female at birth [AFAB]) utilized total body dual-energy x-ray absorptiometry to evaluate BMD Z-scores, and associations between GnRHa duration, body mass index (BMI), and BMD. Participants on GnRHa alone (n = 19, 14 assigned male at birth [AMAB], 5 AFAB) at the time of the study visit were 13.8 [12.8, 15.3] (median [IQR]) years old, had been on GnRHa for 10 [5.5, 19.5] months, and began GnRHa at age 12 [10.4, 12.6] years. Total body BMD Z-score for individuals on GnRHa monotherapy was -0.10 [-0.8, 0.4] (AFAB, female norms) and -0.65 [-1.4, 0.22] (AMAB, male norms). AFAB participants (n = 21) on testosterone were age 16.7 [15.9, 17.8] years, had been on testosterone for 11 [7.3, 14.5] months, and started testosterone at age 16 [14.8, 16.8] years; total body BMD Z-score -0.2 [-0.5, 0] (male norms) and 0.4 [-0.2, 0.7] (female norms). AMAB participants (n = 16) were age 16.2 [15.1, 17.4] years, had been on estradiol for 11 [5.6, 13.7] months, and started estradiol at age 16 [14.4, 16.7] years; total body BMD Z-score -0.4 [-1.1, 0.3] (male norms) and -0.2 [-0.7, 0.6] (female norms). BMD Z-score was negatively correlated with GnRHa duration (male norms: r = -0.5, P = .005; female norms: r = -0.4, P = .029) and positively correlated with BMI (male norms: r = 0.4, P = .003; female norms: r = 0.4, P = .004). In this cross-sectional cohort, total body BMD Z-scores were slightly below average, but lowest in the AMAB group on GnRHa monotherapy.