Gender-affirming Hormone Treatment Research Articles

Histological ovarian features and hormonal determinations in assigned females at birth transgender individuals according to different testosterone preparations

IntroductionDistinct androgen formulations have been used as gender-affirming hormone treatment, but little is known about the specific changes that may occur in the ovary depending on the testosterone preparation used. The study aims to evaluate the histological modifications of the ovarian tissue and the hormonal changes after gender-affirming surgery based on the testosterone preparation employed, such as testosterone cypionate or undecanoate.DesignUnicenter transversal cohort study.Materials and methodsSixty transmasculine persons before and after gender-affirming surgery. A histological examination of the ovaries was conducted, including the follicular population and the characterization of the ovarian stroma. Hormonal status (testosterone, estradiol, FSH, and LH) were also assessed before and after the procedure.ResultsThe median age of participants was similar between the two groups (27.9 vs. 26.7 years, p = 0.27). There were no differences in all hormonal determinations before gender-affirming surgery between the groups. After surgery, FSH levels increased significantly, especially in the testosterone undecanoate group compared to the cypionate group (72.3 vs. 38.3 U/L, p = 0.02), consistent with LH determinations (43.0 vs. 23.4 U/L, p = 0.02). However, no regimen modification was required for any individual. No statistical differences were observed in any parameter concerning the follicular population, nor were there any variances in the thickness of the tunica albuginea (p = 0.85) or the proportion of luteinized stromal cells. Nevertheless, there was a tendency toward increased luteinization in the testosterone cypionate group (88.2% vs. 76.9%, p > 0.05).ConclusionsIn a cohort of transmasculine individuals using different androgen preparations, histological analysis of ovarian tissue revealed comparable findings. Both groups exhibited similar follicular populations and comparable modifications in stromal tissue. However, significant differences were observed in hormonal profiles, although no modification in testosterone dosage was needed.

Cardiometabolic risk assessment in transgender individuals - differential impact of sex hormones and sex chromosomes.

While transgender individuals represent a significant group seeking medical care, the differential effect of sex on cardiometabolic risk metrics is incompletely understood. Therefore, the current study aimed to characterize the impact of sex hormones and chromosomes on a contemporary panel of cardiometabolic risk biomarkers and functional cardiovascular measurements. 17 transmen and 17 transwomen were studied at baseline (T0), 4 weeks (hormonal castration, T1), and 11 months following gender-affirming hormone treatment (T12). We analyzed carotid intima-media thickness (cIMT) and arterial stiffness, lipoproteins and other metabolites comprehensively by nuclear magnetic resonance spectroscopy and HDL-mediated cholesterol efflux capacity (CEC) from macrophages. T0 to T12 comparisons informed the impact of sex hormones, comparisons of genetic XX and XY individuals at T1 the impact of sex chromosomes. Vascular function was comparable at T12 and T0; systolic blood pressure increased in transmen (p=0.002). Transmen developed a pro-atherogenic lipoprotein profile, estrogen treatment in transwomen tended to result in improvements. Several metabolites indicating increased diabetes risk including plasma glucose were changed in transmen (p=0.025), with opposite changes in transwomen (p=0.002). Interestingly, at T1 apparent diabetes risk was lower in XX compared with XY individuals (p=0.002). CEC decreased in transwomen (p<0.01), while remaining unchanged in transmen. However, in both groups the strong positive association of apoA-I with cholesterol efflux observed at T0 was lost at T12. The results are consistent with increased cardiometabolic risk in transmen, while transwomen show beneficial changes early during gender-affirming hormone therapy. Sex chromosomes have less intrinsic effects. XY individuals and transmen display an increased apparent diabetes risk. Further research of cardiometabolic risk is needed for transgender individuals.

United Kingdom data collection of semen quality in transgender adolescent females seeking fertility preservation

ObjectiveIncreasing numbers of adolescents with gender dysphoria start gonadotropin-releasing hormone agonists to halt puberty, minimising psychological distress. The uncertainty of long-term effects of this medication, and the subsequent likelihood of accessing gender affirming hormone treatment, highlights the importance of fertility preservation prior to starting hormone treatment. We investigated the take up, hormonal profile and sperm quality in adolescents undergoing fertility preservation via cryopreservation by masturbation or surgical sperm retrieval, prior to starting hormonal therapy. DesignData was prospectively maintained from a tertiary UK-based hospital. 122 people under 19 years, mean age 15.2 +/- 1.7 years, referred by gender clinics and GPs, were included in this cohort study. SubjectsParticipants were counselled for fertility preservation, and serum testosterone, follicle stimulating hormone, and luteinizing hormone levels were recorded prior to providing semen samples. InterventionMasturbation semen samples were classified as normal (>15mil/ml), oligozoospermia (1mil-15mil/ml), cryptozoospermia (<1mil/ml) or azoospermia. If the sample was insufficient or the person was unwilling to masturbate, surgical sperm retrieval was offered in a stepwise manner using electroejaculation, TESE +/- mTESE. Main Outcome measurementsQuality of semen produced by participants, via masturbation or surgical sperm retrieval, was analysed to determine if it was good enough to cryopreserve for future fertility use. Results23/122 (19%) participants declined sample storage.In the masturbation group (average age 16.3), 78 people produced 106 samples. 86/106 were stored - 43.7% were normospermic, 35.9% oligozoospermic, 8.7% cryptozoospermic, 11.7% azoospermic. Overall, semen parameters varied but were generally abnormal, illustrated by only 43.7% of the masturbation samples produced being normospermic.For surgical sperm retrieval subjects (average age 15.2), electroejaculation was successful in 4/21 people, while the rest proceeded with TESE/mTESE. Encouragingly, 16/21 subjects had an average of 5 vials stored, and all participants had a testosterone level >8nmol/l. Semen parameters in this sub-cohort were poor but possibly adequate for intracytoplasmic sperm injection. ConclusionsIn this large database of transgender girls referred for fertility preservation in the UK, fertility preservation is possible, even with those unwilling to masturbate. Long-term data is required to check the health of these gametes, observing live birth rates using these preserved gametes.

Gender Reassignment and the Role of the Laboratory in Monitoring Gender-Affirming Hormone Therapy.

Transgender people experience distress due to gender incongruence (i.e., a discrepancy between their gender identity and sex assigned at birth). Gender-affirming hormone treatment (GAHT) is a part of gender reassignment treatment. The therapeutic goals of the treatment are to develop the physical characteristics of the affirmed gender as far as possible. Guidelines have been developed for GAHT, which recommend dosage as well as different formulations of oestrogen and testosterone for treatment. Questions arise about the metabolic side effects of hormone treatment. Establishing reference ranges for common analytes in transgender individuals remains a task for laboratory medicine. It has been suggested once GAHT is commenced, the reference ranges for affirmed gender are reported for red blood cells, haemoglobin and haematocrit. For transgender assigned-female-at-birth (AFAB) people, testosterone concentrations are recommended to be within the reference interval established for cisgender men and for transgender assigned-male-at-birth (AMAB) people, estradiol concentrations are within the reference range for cisgender women. Sex-specific reference ranges are available for certain laboratory tests, and these may be organ (e.g., heart)-specific. Transgender-specific reference ranges may be a requirement for such tests. Laboratories may need to make decisions on how to report other tests in the transgender population, e.g., eGFR. Interpretation of further tests (e.g., reproductive hormones) can be individualized depending on clinical information. Electronic medical record systems require fields for gender identity/biological sex at birth so that laboratory results can be flagged appropriately. In this review, we aim to summarise the current position of the role of the laboratory in the clinical care of the transgender individual. Prior to the review, we will summarise the genetics of sex determination, the aetiology of gender incongruence, and the recommendations for GAHT and monitoring for the transgender population.

Parental perspectives on fertility preservation for their trans and gender-expansive children: Reflections on complexities of autonomy, support, and societal realities

Introduction Navigating fertility preservation poses unique challenges for young transgender and gender expansive (TGE) youths, who must balance short-term concerns like delaying gender-affirming hormonal treatment (GAHT) with long-term considerations of potential infertility. Parents play a crucial role in supporting their TGE children through their gender affirmation journey, which includes discussions about fertility preservation. Aim This study aimed to explore parental feelings and attitudes toward the fertility preservation of their TGE children, acknowledging the diverse perspectives shaped by societal, legal, and personal factors. Methods The study involved 82 parents who completed an online-distributed questionnaire. Participants were parents of TGE youths aged between six and twenty-five years old. The mixed-methods study utilized a tailored questionnaire comprising both open-ended and closed-ended questions. Results Descriptive analysis revealed that a significant majority of parents were aware of the effects of GAHT on fertility, with 65.3% expressing a desire for their children to have their own children in the future. However, parents shared that only 14.5% of children underwent a fertility preservation pathway, while 68.1% did not, citing barriers such as lack of services, cost, and procedural distress. Qualitative analysis identified four main themes: (1) Emotional response, (2) Parental expectations, (3) Parent-Child relationship, and (4) Structural barriers. Discussion Overall, the study underscores the multifaceted nature of parental experiences regarding fertility preservation for TGE individuals, emphasizing the importance of addressing societal norms, personal expectations, and structural barriers to ensure equitable access to reproductive healthcare services.

Effect of testosterone formulations on hematocrit in transgender individuals: A systematic review.

Approximately, 11% of trans men experience erythrocytosis diagnosis due to testosterone administration during the first year of the gender-affirming hormone treatment (GAHT). To identify and compare the effect of different testosterone formulations on hematocrit (Hct) and diagnose erythrocytosis in trans men. This systematic review was based on PRISMA guidelines. We performed an electronic search of PubMed, Embase, and Web of Science in January 2024. The Newcastle-Ottawa scale was used to evaluate the quality of evidence in the observational studies. Of the 152 records retrieved, 18 met the eligibility criteria. Studies observed an increase of up to 5% in Hct in trans men using injectable testosterone undecanoate (TU), and up to 6.9% in trans men using intermediate injectable testosterone esters (TE). Trans men using TE experience a larger increase in serum Hct levels compared to those receiving TU. Erythrocytosis prevalence varies according to the cutoff used (50%, 52%, and 54%). Erythrocytosis was also associated with tobacco use, age at initiation of hormone therapy, body mass index (BMI), and pulmonary conditions. Studies that evaluated the effect of testosterone formulation on erythrocytosis diagnosis present conflicting result. Trans men have a hazard ratio of 7.4 (95% CI: 4.1, 13.4) of developing erythrocytosis compared to cisgender men, using a 52% hematocrit cutoff. All testosterone formulations result in an increase in Hct, irrespective of dose, formulation, and administration method. Smoking, higher age at initiation of the testosterone therapy, higher BMI, and a predisposing medical history are associated with this increase in Hct. The difference in effect of TE and TU on Hct is conflicting, although it is important to point out that these data come from observational studies, retrospective, and with a small-sample size.

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.

Transgender healthcare: metabolic outcomes and cardiovascular risk.

Transgender identity is often associated with gender dysphoria and minority stress. Gender-affirming hormone treatment (GAHT) includes masculinising or feminising treatment and is expected to be lifelong in most cases. Sex and sex hormones have a differential effect on metabolism and CVD in cisgender people, and sex hormone replacement in hypogonadism is associated with higher vascular risk, especially in ageing individuals. Using narrative review methods, we present evidence regarding metabolic and cardiovascular outcomes during GAHT and propose recommendations for follow-up and monitoring of metabolic and cardiovascular risk markers during GAHT. Available data show no increased risk for type 2 diabetes in transgender cohorts, but masculinising GAHT increases lean body mass and feminising GAHT is associated with higher fat mass and insulin resistance. The risk of CVD is increased in transgender cohorts, especially during feminising GAHT. Masculinising GAHT is associated with a more adverse lipid profile, higher haematocrit and increased BP, while feminising GAHT is associated with pro-coagulant changes and lower HDL-cholesterol. Assigned male sex at birth, higher age at initiation of GAHT and use of cyproterone acetate are separate risk factors for adverse CVD markers. Metabolic and CVD outcomes may improve during gender-affirming care due to a reduction in minority stress, improved lifestyle and closer surveillance leading to optimised preventive medication (e.g. statins). GAHT should be individualised according to individual risk factors (i.e. drug, dose and form of administration); furthermore, doctors need to discuss lifestyle and preventive medications in order to modify metabolic and CVD risk during GAHT. Follow-up programmes must address the usual cardiovascular risk markers but should consider that biological age and sex may influence individual risk profiling including mental health, lifestyle and novel cardiovascular risk markers during GAHT.

O-116 Fertility in transmasculine people

Abstract Transgender and gender diverse (TGD) people apply for gender-affirming care at any age to manage gender identities or expressions that differ from the gender socially attributed to their sex assigned at birth. Gender-affirming hormonal treatment (GAHT) and gender-affirming surgery (GAS) may alter reproductive function and/or anatomy, limiting future reproductive options to varying degrees, if persons have the wish to either give birth and, or to become a biological parent. The desire to have children in TGD people does not differ from that of the cis population. In those persons assigned female at birth but who identify as male or genderdivers medical transition often comprises testosterone to induce masculinisation. The effect of testosterone on the uterus and ovaries and further reproductive outcome has not been fully clarified so far. There are several histological studies showing ovarian cortical and stromal changes following testosterone exposure, it is uncertain what the consequences for future fertility may be. It seems there is persistent activity in folliculogenesis by the descriptions of follicle count, distribution and oocyte retrieval. However, there are studies showing a negative effect on fertilization rate in presence of testosterone. Reports on successful ovarian stimulation, fertilizations, pregnancies and live births have been published, with and without testosterone discontinuation. In this lecture an overview will be given of the recent literature and guidelines on fertility outcome in TGD people assigned female at birth, specifically the effect of medical transition. Recommendations on counseling and ways of fertility preservation will be discussed.

Gender-Affirming Hormone Treatment and Metabolic Syndrome Among Transgender Veterans.

Gender-affirming hormone treatment (GAHT) is a common therapy for transgender individuals to reduce gender dysphoria and improve quality of life. Clarifying the long-term effects of GAHT remains a priority in transgender health research. To explore whether sex hormones (estradiol and testosterone) are associated with the development of metabolic syndrome in transgender veterans compared with cisgender veterans. This retrospective, longitudinal cohort study used International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes for gender dysphoria from the Veterans Health Administration national database to identify transfeminine and transmasculine veterans receiving documented feminizing (estradiol) or masculinizing (testosterone) treatment from January 1, 2006, to December 31, 2019, and for whom the GAHT initiation date and metabolic syndrome component-related data were available. Transgender veterans were matched to cisgender referents. Gender-affirming hormone treatment. Metabolic syndrome z-scores were calculated based on body mass index, systolic blood pressure, and levels of high-density lipoprotein cholesterol, triglycerides, and blood glucose. Changes in mean z-scores were compared among the transgender and cisgender groups before and after the index date (corresponding to GAHT initiation) using a repeated-measures analysis of variance model. The cohort included 1290 participants: 645 transgender (494 [38.3%] transfeminine, 151 [11.7%] transmasculine) and 645 cisgender (280 [21.7%] female, 365 [28.3%] male). Mean (SD) age at the index date was 41.3 (13.2) years. Metabolic syndrome z-scores changed significantly over time and differed significantly across groups. Overall, transmasculine veterans had the greatest percentage increase in mean (SEM) z-scores after vs before the index date (298.0% [57.0%]; P < .001), followed by cisgender females (108.3% [27.5%]; P < .001), cisgender males (49.3% [27.5%]; P = .02), and transfeminine persons (3.0% [10.7%]; P = .77). In this cohort study, in both cisgender and transgender veterans, estradiol was associated with reduced metabolic syndrome risk, whereas testosterone was associated with increased risk. However, transmasculine individuals had the greatest risk and transfeminine individuals had the lowest risk of metabolic syndrome associated with these hormones. This is relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals and to potentially predict the risk of atherosclerotic cardiovascular disease, type 2 diabetes, systolic hypertension, insulin resistance, and nonalcoholic fatty liver disease.

Functional Changes to Achilles Tendon and Enthesis in a Mouse Model of an Adolescent Masculine Gender-Affirming Hormone Treatment.

Many transgender youth seek gender affirming care, such as puberty suppression, to prolong decision-making and to align their physical sex characteristics with their gender identity. During peripubertal growth, connective tissues such as tendon rapidly adapt to applied mechanical loads (e.g., exercise) yet if and how tendon adaptation is influenced by sex and gender affirming hormone therapy during growth remains unknown. The goal of this study was to understand the how pubertal suppression influences the structural and functional properties of the Achilles tendon using an established mouse model of transmasculine gender affirming hormone therapy. C57BL/6N female-born mice were assigned to experimental groups to mimic gender-affirming hormone therapy in human adolescents, and treatment was initiated prior to the onset of puberty (at postnatal day 26, P26). Experimental groups included controls and mice serially treated with gonadotropin release hormone analogue (GnRHa), delayed Testosterone (T), or GnRHa followed by T. We found that puberty suppression using GnRHa, with and without T, improved the overall tendon load capacity in female-born mice. Treatment with T resulted in an increase in the maximum load that tendon can withstand before failure. Additionally, we found that GnRHa, but not T, treatment resulted in a significant increase in cell density at the Achilles enthesis.

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.

Co-design and usability of an interactive web-based fertility decision aid for transgender youth and young adults.

To develop a patient- and family-centered Aid For Fertility-Related Medical Decisions (AFFRMED) interactive website targeted for transgender and nonbinary (TNB) youth/young adults and their parents to facilitate shared decision-making about fertility preservation interventions through user-centered participatory design. TNB youth/young adults interested in or currently receiving pubertal suppression or gender-affirming hormone treatment and parents of eligible TNB youth/young adults were recruited to participate in a series of iterative human-centered co-design sessions to develop an initial AFFRMED prototype. Subsequently, TNB youth/young adults and parents of TNB youth/young adults were recruited for usability testing interviews, involving measures of usability (i.e., After Scenario Questionnaire, Net Promotor Score, System Usability Scale). Twenty-seven participants completed 18 iterative co-design sessions and provided feedback on 10 versions of AFFRMED (16 TNB youth/young adults and 11 parents). Nine TNB youth/young adults and six parents completed individual usability testing interviews. Overall, participants rated AFFRMED highly on measures of acceptability, appropriateness, usability, and satisfaction. However, scores varied by treatment cohort, with TNB youth interested in or currently receiving pubertal suppression treatment reporting the lowest usability scores. We co-created a youth- and family-centered fertility decision aid prototype that provides education and decision support in an online, interactive format. Future directions include testing the efficacy of the decision aid in improving fertility and fertility preservation knowledge, decisional self-efficacy, and decision satisfaction.

Body Composition and Metabolic Syndrome Components in Transgender/Gender Diverse Adolescents and Young Adults.

Purpose: The objective of this study was to examine the association of designated sex at birth, body composition, and gender-affirming hormone treatment (GAHT) with the components of metabolic syndrome (MetS) (overweight/obesity, elevated blood pressure [BP], altered glucose metabolism, and dyslipidemia) in transgender/gender diverse (TGD) adolescents and young adults. Methods: TGD individuals underwent body composition studies by bioelectrical impedance analysis according to designated sex at birth, and their muscle-to-fat ratio (MFR) z-scores were calculated. Generalized estimating equations with binary logistic models (n = 326) were used to explore associations while adjusting for potential confounders. Results: A total of 55 TGD females and 111 TGD males, with mean age of 18 ± 1.9 years and median duration of GAHT of 1.4 years (interquartile range = 0.6-2.5), were enrolled. Overall, 118/166 (71%) of the TGD cohort showed evidence of at least one MetS component, with a significantly higher rate among TGD males compared with TGD females (91.1% vs. 50.9%, p < 0.001). TGD males were at increased odds for overweight/obesity, elevated/hypertensive BP, elevated triglycerides (TGs), and an atherogenic dyslipidemia index (TG/high-density lipoprotein cholesterol [HDL-c], TG:HDL-c). The odds of overweight/obesity increased by 44.9 for each standard deviation decrease in the MFR z-score, while the odds for an elevated TG:HDL-c index increased by 3.7. Psychiatric morbidity increased the odds for overweight/obesity by 2.89. Conclusions: After considering confounding variables, the TGD males on GAHT were found to be at an increased risk for cardiometabolic disease. Our observations support the importance of targeted medical nutrition intervention in this group of individuals.

Puberty Blocker, Leuprolide, Reduces Sex Differences in Rough-and-Tumble Play and Anxiety-like Behavior in Juvenile Rats.

We examined the effect of the puberty blocker, leuprolide acetate, on sex differences in juvenile rough-and-tumble play behavior and anxiety-like behavior in adolescent male and female rats. We also evaluated leuprolide treatment on gonadal and pituitary hormone levels and activity-regulated cytoskeleton-protein messenger RNA levels within the adolescent amygdala, a region important both for rough-and-tumble play and anxiety-like behavior. Our findings suggest that leuprolide treatment lowered anxiety-like behavior during adolescent development, suggesting that the maturation of gonadotropin-releasing hormone systems may be linked to increased anxiety. These data provide a potential new model to understand the emergence of increased anxiety triggered around puberty. Leuprolide also reduced masculinized levels of rough-and-tumble play behavior, lowered follicle-stimulating hormone, and produced a consistent pattern of reducing or halting sex differences of hormone levels, including testosterone, growth hormone, thyrotropin, and corticosterone levels. Therefore, leuprolide treatment not only pauses sexual development of peripheral tissues, but also reduces sex differences in hormones, brain, and behavior, allowing for better harmonization of these systems following gender-affirming hormone treatment. These data contribute to the intended use of puberty blockers in stopping sex differences from developing further with the potential benefit of lowering anxiety-like behavior.

Adipokine secretion and lipolysis following gender-affirming treatment in transgender individuals

BackgroundThe organ-specific effects of gender-affirming sex hormone treatment (GAHT) in transgender women (TW) and transgender men (TM) are insufficiently explored. This study investigated the effects of GAHT on adipose tissue function.MethodsIn a single-center interventional prospective study, 32 adults undergoing GAHT, 15 TW and 17 TM, were examined with anthropometry and abdominal subcutaneous adipose tissue biopsies obtained before initiation of treatment, 1 month after endogenous sex hormone inhibition and three and 11 months after initiated GAHT. Fat cell size, basal/stimulated lipolysis and cytokine secretion in adipose tissue were analyzed.ResultsTW displayed an increase in complement component 3a and retinol-binding protein 4 (RBP4) secretion after sex hormone inhibition, which returned to baseline following estradiol treatment. No changes in lipolysis were seen in TW. TM showed downregulation of RBP4 after treatment, but no changes in basal lipolysis. In TM, the estrogen suppression led to higher noradrenaline stimulated (NA) lipolysis that was normalized following testosterone treatment. At 11 months, the ratio of NA/basal lipolysis was lower compared to baseline. There were no significant changes in fat cell size in either TW or TM.ConclusionIn TW, gonadal hormone suppression results in transient changes in cytokines and in TM there are some changes in NA-stimulated lipolysis following testosterone treatment. However, despite the known metabolic effects of sex hormones, the overall effects of GAHT on adipose tissue function are small and likely have limited clinical relevance, but larger studies with longer follow-up are needed to confirm these findings.Trial registrationClinicalTrials.gov Identifier: NCT02518009, Retrospectively registered 7 August 2015.

Reidentification With Birth-Registered Sex in a Western Australian Pediatric Gender Clinic Cohort

Some young people who identify as transgender and seek gender-affirming medical care subsequently reidentify with their sex registered at birth. Evidence regarding the frequency and characteristics of this experience is lacking. To determine the frequency of reidentification and explore associated characteristics in a pediatric gender clinic setting. This retrospective cohort study examined all referrals to the Child and Adolescent Health Service Gender Diversity Service at Perth Children's Hospital between January 1, 2014, and December 31, 2020. The Gender Diversity Service is the sole statewide specialist service in Western Australia that provides children and adolescents up to age 18 years with multidisciplinary assessment, information, support, and gender-affirming medical care. All closed referrals for this study were audited between May 1, 2021, and August 8, 2022. Reidentification with birth-registered sex. The number of referrals closed due to reported reidentification with birth-registered sex was determined, as well as descriptives and frequencies of patient demographics (age, birth-registered sex), informant source, International Statistical Classification of Diseases, Tenth Revision gender-related diagnoses, pubertal status, any gender-affirming medical treatment received, and whether subsequent re-referrals were received. Of 552 closed referrals during the study period, a reason for closure could be determined for 548 patients, including 211 birth-registered males (mean [SD] age, 13.88 [2.00] years) and 337 birth-registered females (mean [SD] age, 15.81 [2.22] years). Patients who reidentified with their birth-registered sex comprised 5.3% (29 of 548; 95% CI, 3.6%-7.5%) of all referral closures. Except for 2 patients, reidentification occurred before or during early stages of assessment (93.1%; 95% CI, 77.2%-99.2%). Two patients who reidentified with their birth-registered sex did so following initiation of puberty suppression or gender-affirming hormone treatment (1.0% of 196 patients who initiated any gender-affirming medical treatment; 95% CI, 0.1%-3.6%). These findings from a pediatric gender clinic audit indicate that a small proportion of patients, and a very small proportion of those who initiated medical gender-affirming treatment, reidentified with their birth-registered sex during the study period. Longitudinal follow-up studies, including qualitative self-report, are required to understand different pathways of gender identity experience.

Effects of gender affirming hormone treatment in transgender individuals - a retrospective cohort study.

Gender affirming hormone treatment (GAHT) results in measurable changes to anthropomorphic, biochemical and hormonal variables that are important to patients and their health care professionals to guide treatment. This study sought to quantify changes which occur in response to initiation of GAHT. We performed a retrospective cohort study of outcomes in transgender and gender diverse (TGD) patients starting GAHT. The primary outcome was proportion of patients and time required to achieve optimal hormone levels after commencement of GAHT. Additional analyses were performed to assess whether clinical and biochemical factors were associated with likelihood of achieving target hormone levels. 345 patients were included. Among 154 transmasculine individuals, 116 (75%) achieved a testosterone level >10 nmol/L during follow-up at a median of 4-months (IQR 4-9). No clinical or biochemical factors were significantly associated with likelihood of reaching therapeutic testosterone concentrations in transmen. Among 191 transfeminine individuals, 131 (72%) achieved a testosterone level <2.0 nmol/L during follow-up at a median of 4-months (IQR 3-9). Factors associated with increased likelihood of testosterone suppression were use of subdermal estradiol implants as well as cyproterone acetate as an androgen antagonist. Changes in differing directions were observed during repeated measures of lipids, liver function, and blood count between transmasculine and transfeminine individuals, reflecting the important effects of testosterone and estradiol on biochemical tests ordered as part of routine clinical care. Most TGD patients achieve target testosterone levels within 9 months of GAHT initiation. Adverse effects of GAHT are rare, and are usually mild.

Nonprescription Hormone Use Among Transgender Women - National HIV Behavioral Surveillance Among Transgender Women, Seven Urban Areas, United States, 2019-2020.

Certain transgender women who seek gender-affirming hormone treatment (GAHT) face economic and social barriers that limit or prevent access to medically supervised GAHT. Transgender women facing such barriers might acquire GAHT without prescription, potentially without proper dosage, administration, and health monitoring in the absence of medical supervision. For this report, survey data were analyzed from 1,165 transgender women in seven urban areas in the United States to examine associations between self-reported use of nonprescription GAHT and known correlates of nonprescription GAHT, including cost, insurance coverage for GAHT, homelessness, receiving money or drugs in exchange for sex during the past 12 months (exchange sex), lack of comfort discussing gender with provider, and lack of health care use. After controlling for complex sampling design, transgender women who reported recent health care use or insurance coverage for GAHT were less likely to report nonprescription GAHT, and those reporting recent exchange sex or recent homelessness were more likely to report nonprescription GAHT. Findings suggest that transgender women were more likely to use GAHT without a prescription in situations of economic and social marginalization (e.g., disengagement from health care, lack of insurance or trans-specific health care, homelessness, or engagement in sex work). Public health professionals can use these results to design effective interventions to facilitate prescribed hormone use among transgender women in the United States, although access to housing, trans-affirming health care, and insurance coverage might be needed to prevent nonprescription use.

Gender Affirming Hormone Treatment for Trans Adolescents: A Four Principles Analysis

Gender affirming hormone treatment is an important part of the care of trans adolescents which enables them to develop the secondary sexual characteristics congruent with their identified genders. There is an increasing amount of empirical evidence showing the benefits of gender affirming hormone treatment for psychological health and social well-being in this population. However, in several countries, access to gender affirming hormone treatment for trans adolescents has recently been severely restricted. While much of the opposition to gender affirming hormone treatment for trans adolescents has in part been ideologically motivated, it also reflects a debate about whether there are harms that outweigh the benefits of the treatment. Accordingly, a systematic and comprehensive philosophical analysis of the ethics of gender affirming hormone treatment for trans adolescents is needed. Herein, I offer such an analysis that draws on the four principles of biomedical ethics by Tom Beauchamp and James Childress. Based on the considerations of beneficence, nonmaleficence, autonomy, and justice, I argue that the provision of access to gender affirming hormone treatment for consenting trans adolescents is ethically required and that the current restrictions to such treatment are ethically wrong.