Transgender individuals undergo the gender-affirming hormone therapy (GAHT) to achieve physical changes consistent with their gender identity. Few studies are available on the long-term safety and efficacy of GAHT.

To investigate the long-term physical effects and the safety of the testosterone therapy for trans men and to assess the impact of differential hormone dose.

Trans men who initiated GAHT between May 2000 and December 2021 were included in this retrospective analysis. Physical findings (body mass index, body fat percentage (BFP), lean body mass (LBM), and grip strength), blood testing results (hemoglobin, hematocrit, uric acid, creatinine, total cholesterol, triglycerides, and total testosterone), and menstrual cessation were recorded. We assessed the effects of testosterone on body composition changes and laboratory parameters, comparing a low-dose group (≤ 62.5 mg/wk) to a high-dose group (> 62.5 mg/wk).

Of 291 participants, 188 patients (64.6%) were in the low-dose group and 103 (35.4%) in the high-dose group. Cumulative menstrual cessation rates up to 12 months were not significantly different between groups. Both groups showed a decrease in BFP and an increase in LBM during the first year of therapy, followed by a slight increase in both over the long term. The high-dose group exhibited greater LBM gains during the first year. Higher hormone doses and lower initial LBM values were associated with LBM increases at 3 and 6 months (3 mo, P = 0.006, P < 0.001; 6 mo, P = 0.015, P < 0.001). There were no long-term, dose-dependent side effects such as polycythemia or dyslipidemia.

Long-term GAHT for trans men is safe and effective. Low-dose testosterone administration is sufficient to increase LBM in trans men. Higher testosterone doses can lead to an earlier increase in muscle mass.

Previous studies show that transgender and gender-diverse (TGD) individuals, especially those assigned male at birth (AMAB), often have low bone mineral density (BMD) before beginning gender-affirming hormone therapy (GAHT). The reasons for this are not fully understood, and the potential role of androgen receptor (AR) polymorphisms - known to affect bone density in the general population - has not been explored. This study aims to assess the impact of AR polymorphisms on bone health in the TGD population.

This is an observational study involving 135 TGD and 107 cisgender participants. Collected data included hormonal profiles and phospho-calcium metabolism, bone geometry and density (Dual Energy X-ray Absorptiometry and peripheral Quantitative Computed Tomography). For the genetic study related to the AR, genomic DNA was extracted from peripheral blood leukocytes.

TGD individuals had lower BMD values compared to their cisgender peers. In a subgroup of 129 individuals (86 TGD and 43 cisgender), we assessed the length of the polymorphic tracts of the AR gene and observed no differences between the groups. AR polymorphisms showed significant correlations only with cortical BMD in both TGD and cisgender assigned females at birth (AFAB) individuals, and negative correlations with trabecular BMD in both cisgender men and women.

Our study suggests that AR polymorphisms do not play a significant role in the low BMD values observed in TGD individuals at baseline. Further research is necessary to better understand the impact of factors such as lifestyle on the bone health of TGD individuals.

There is a paucity of data on the safety and efficacy of long-term testosterone (T)-based gender-affirming hormone therapy (GAHT) on anthropometric parameters, body composition, and glycolipid metabolism in assigned female at birth (AFAB) persons. The purpose of this study was to provide an updated meta-analysis on this topic.

We searched PubMed, Scopus, and Cochrane Library for relevant studies. Pre-/post-therapy changes in body mass index (BMI), waist-to-hip ratio (WHR), body composition, lipid glycemic/insulinemic profiles were combined as mean differences (MD) with 95% confidence interval (CI), using random-effect models.

Thirty-nine studies (N=1949) were analyzed. At pooled estimates, GAHT was associated with significant decrease in fat mass (MD: -1.29 kg; 95% CI: -2.52 to -0.05; p=0.04) and increase in lean mass (4.12 kg; 95% CI: 3.07-5.16; p<0.00001), BMI (0.78 kg/m2; 95% CI: 0.50-1.07; p<0.00001), and WHR (0.02; 95%CI: 0.01-0.03; p=0.003) in the absence of heterogeneity (I 2=0%). T therapy was also accompanied by unfavorable effects on lipid profile, including increases in total cholesterol (4.95 mg/dL; 95% CI: 1.53-8.37; p=0.005), LDL (11.15 mg/dL; 95% CI: 7.57-14.74; p<0.00001), and triglycerides (9.49 mg/dL; 95% CI: 4.39-14.58; p=0.0003) and decrease in HDL concentration (-7.52 mg/dL; 95% CI: -9.38 to -5.67; p<0.00001). Finally, T therapy resulted in a significant decrease in blood glucose concentration (-2.06 mg/dL; 95% CI: -3.37 to -0.74; p=0.002), with no significant effects on homeostatic model assessment index of insulin resistance.

T-based GAHT in AFAB people is associated with androgenic changes in body composition and body fat distribution, accompanied by the acquisition of a more unfavorable cardiovascular lipid profile.

Transgender medicine has become rapidly recognized and evolving in the health care system. The consequences of hormone therapy are among the most concerning health issues in the transgender population. This study aims to compare bone turnover markers before and after testosterone administration in hormone-naive transgender men.

This prospective study included 20 hormone-naive transgender men. Comparisons of serum C-terminal cross-linking telopeptide of type I collagen (CTX) at baseline with 12 weeks and 24 weeks were analyzed using Wilcoxon signed-rank test. Serum procollagen type I N-propeptide (P1NP) and osteocalcin levels at 24 weeks compared to baseline were also assessed. Pearson's correlation coefficient analysis was used to compare the correlation between serum bone turnover markers and sex hormone levels.

At 12 weeks after testosterone administration, significant higher serum CTX level compared to baseline (p-value 0.035) was demonstrated. At 24 weeks after testosterone administration, there were significant differences in serum CTX, P1NP, and osteocalcin levels compared to baseline (p-value 0.019, <0.001, and 0.003, respectively). Serum CTX, P1NP, and osteocalcin levels significantly increased 28.30%, 44.26%, and 21.89%, respectively, at 24 weeks after testosterone treatment. There was a moderate negative correlation between serum CTX and estradiol level.

Testosterone administration in transgender men significantly increased the levels of bone turnover markers. Further, well-controlled studies of bone health in transgender men are required to prove and assess the other aspects of bone status over a long-term follow-up period.Thai Clinical Trial Registry identification number TCTR20220817002.

Higher stress levels are linked to increased body fat and decreased bone density, effects that can be exacerbated by lifestyle choices. This is particularly relevant for transgender and gender diverse (TGD) individuals, who often face additional stress from transphobia and social stigma. However, there is limited research on how stress affects body composition and bone health in TGD individuals, particularly in relation to gender-affirming hormone therapy (GAHT). This study examines the impact of perceived stress on these factors in TGD individuals before and after one year of GAHT, compared to a cisgender control group.

The study assessed 181 individuals, including 74 TGD participants (44 assigned female at birth [AFAB] and 30 assigned male at birth [AMAB]) and 107 controls (56 AFAB and 51 AMAB). Fifty-seven TGD participants completed follow-up one year after starting GAHT. Data collected included clinical history, blood tests, body composition, bone density, and quality of life assessments (Patient Health Questionnaire-9 [PHQ-9] and Perceived Stress Scale [PSS]).

After one year of GAHT, TGD AFAB individuals showed a bone mineral density (BMD) similar to cisgender AMAB individuals, while TGD AMAB individuals' BMD remained significantly lower than cisgender controls. TGD AFAB individuals experienced increases in muscle strength (+8% from baseline), while TGD AMAB individuals showed a 24% increase in fat mass from baseline and an approximate 8% reduction in lean mass. PSS and PHQ scores, initially higher in TGD individuals, did not change significantly after one year of GAHT. A significant correlation was found between body fat percentage and PHQ and PSS scores at baseline and one year after GAHT, respectively.

These findings reveal a complex relationship between GAHT, body composition, and perceived stress in TGD individuals, highlighting the need for further research on stress and health outcomes in this population.

Findings from clinical trials have led to advancement of care for patients with gynecologic malignancies. However, restrictive inclusion of patients into trials has been widely criticized for inadequate representation of the real-world population. Ideally, patients enrolled in clinical trials should represent a broader population to enhance external validity and facilitate translation of outcomes across all relevant groups. Specifically, there has been a systematic lack of data for underrepresented groups, with many studies failing to report or differentiate study participants based on sociodemographic domains, such as race and ethnicity. As such, the impact of treatment in these underrepresented groups is poorly understood, and clinical outcomes according to various sociodemographic factors are infrequently assessed. Inclusion of diverse trial participants, with different racial and ethnic background, is essential for the understanding of factors that may impact clinical outcomes. Therefore, we conducted a multi-national meeting of clinical trial groups and industry with the goal of increasing equity, diversity, and inclusion in gynecologic cancer clinical trials and to address barriers to recruitment, participation, and harmonization of data collection and reporting. These Gynecologic Cancer Intergroup (GCIG) statements present recommendations and strategies for the gynecologic cancer research community to improve equity, diversity, and inclusion in gynecologic cancer clinical trials.

Transgender and gender diverse individuals experience a gender identity that differs from the sex assigned at birth. Some transgender men may request testosterone to induce virilization; however, its impact on bone health remains to be fully elucidated. The objective of this systematic review and meta-analysis was to evaluate the modifications in bone metabolism over a short-term period among transgender men initiating testosterone therapy. A systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library. The articles of interest had to report longitudinal evaluation conducted among transgender men, before starting testosterone and after 12 and 24 months of therapy. The analyzed parameters were BMD, calcium, phosphate, 25OHD, PTH, P1NP, BAP, osteocalcin and CTx. Mean differences with 95% coefficient intervals were combined using random effects models. Funnel plot, Egger's test, and trim-and-fill analysis were used to assess publication bias. Fourteen studies met the inclusion criteria, including 1484 subjects. In absence of heterogeneity, BMD did not significantly change at lumbar spine, hip, femoral neck, and whole-body evaluations. Calcium, phosphate, 25OHD and PTH remained stable over time. Regarding bone turnover markers, only P1NP showed a statistically significant increase after 12 months of T therapy, in absence of heterogeneity (SMD 0.61 mcg/l; 95% CI: 0.40-0.83; p < 0.0001; I2 = 0%, Pforheterogeneity = 0.48). Testosterone therapy among transgender men seems not to disrupt bone health after 12 and 24 months. A statistically significant elevation in P1NP levels after 12 months of therapy may indicate a positive anabolic effect of testosterone in the short-term.

Background/Objectives: The current gender-specific nutritional assessment methods for the transgender population may not cover the unique physiological characteristics of the gender transition process. Considering the potential effects of hormone therapy (HT), it has become relevant to review current evidence on the nutritional status of the transgender population. This systematic review aims to provide an updated report of the characteristics of the nutritional status, including food habits, and eating disorders in transgender individuals undergoing HT. Methods: Five databases were researched (PubMed, Web of Science, Scopus, Scielo, and Cochrane Library) from database inception to May 2024. The PRISMA 2020 statement was used. Studies focusing on adult transgender individuals (18 to 65 years old) that included outcomes related to nutritional status, HT, and food habits were considered for this review. The NOS and NIH tools were chosen to perform the risk of bias and quality assessment. Results: A total of 122 studies were identified, and 27 were included in this review. These studies comprised sixteen cohorts, seven cross-sectional, and four case studies, with a combined number of 8827 participants. BMI was the most referenced parameter, varying between low weight and overweight. High food insecurity frequency, restricted eating behaviors, high fat intake, and low levels of vegetable, grain, and fruit consumption were also observed. Conclusions: While nutritional status was perceived as a relevant factor when administering HT, the relationship between HT with both nutritional status and food habits has been insufficiently explored and warrants further research.

Gender-affirming hormone therapy (GAHT) and gender-affirming surgery (GAS) may be desired by transgender and gender-diverse (TGD) individuals who want to affirm their gender identity. Testosterone is the basis of GAHT for transgender individuals assigned female at birth (AFAB), whereas GAS can involve hysterectomy, bilateral salpingectomy, bilateral oophorectomy (BO), thorax masculinization, and phalloplasty. Our study aimed to evaluate the effects of GAHT on the bone health of TGD AFAB individuals who have undergone or not undergone BO.

This was a single-center, longitudinal study with retrospectively collected data. TGD AFAB GAHT-naïve individuals were enrolled and underwent dual-energy X-ray absorptiometry scans and laboratory tests (hormonal and bone metabolism parameters) at baseline and after 5 and 10 years of GAHT.

Two hundred and forty-three TGD AFAB people were included in this study. Seventy-five subjects had completed data for 5 years and 19 subjects for 10 years of GAHT. At baseline, low bone density (Z-score < -2.0) was found in 2.5% (6/243) of subjects for lumbar spine (LS), whereas total hip (TH) and femoral neck (FN) Z-scores and laboratory tests were within the normal female range. After stratifying by physical activity, the physically active group showed significantly higher LS BMD and Z-scores (p ≤ 0.05). Five years after the start of GAHT, a significant reduction in LS (p ≤ 0.05), TH (p ≤ 0.001), and FN (p ≤ 0.01) Z-scores was detected. A significant reduction in the Z-scores of all three bone sites was observed only in the subgroup that had undergone BO. After 5 years of GAHT, estradiol levels were significantly decreased compared to those in baseline (p ≤ 0.001). Significantly higher estradiol levels were detected in the 5-year no-BO subgroup compared to those in the 5-year BO subgroup (p ≤ 0.001). A significant reduction in LS and TH Z-scores were observed after 10 years of GAHT. At this time, estradiol levels were significantly decreased compared to those in baseline (p ≤ 0.01).

Bone density in TGD AFAB individuals is comparable to that in their peers prior to GAHT and BO, but those subjects who underwent BO had a reduced Z-score at LS, FN, and TH after 5 years and at LS after 10 years of GAHT.

Elite individual sports in which success depends on power, speed, or endurance are conventionally divided into male and female events using traditional binary definitions of sex. Male puberty creates durable physical advantages due to the 20- to 30-fold increase in circulating testosterone producing a sustained uplift in men's muscle, bone, hemoglobin, and cardiorespiratory function resulting from male puberty and sustained during men's lives. These male physical advantages provide strong justification for a separate protected category of female events allowing women to achieve the fame and fortune from success they would be denied if competing against men. Recent wider social acceptance of transgender individuals, together with the less recognized involvement of intersex individuals, challenge and threaten to defeat the sex classifications for elite individual female events. This can create unfair advantages if seeking inclusion into elite female events of unmodified male-bodied athletes with female gender identity who have gained the physical advantages of male puberty. Based on reproductive physiology, this paper proposes a working definition of sport sex based primarily on an individual's experience of male puberty and can be applied to transgender and various XY intersex conditions. Consistent with the multidimensionality of biological sex (chromosomal, genetic, hormonal, anatomical sex), this definition may be viewed as a multistrand cable whose overall strength survives when any single strand weakens or fails, rather than as a unidimensional chain whose strength is only as good as its weakest link.

Orthopaedic and sports medicine clinicians can improve outcomes for transgender patients by understanding the physiological effects of gender-affirming hormone therapy (GAHT). This narrative review investigated the role of GAHT on bone mineral density, fracture risk, thromboembolic risk, cardiovascular health and ligament/tendon injury in this population. A search from the PubMed database using relevant terms was performed. Studies were included if they were levels 1-3 evidence. Due to the paucity of studies on ligament and tendon injury risk in transgender patients, levels 1-3 evidence on the effects of sex hormones in cisgender patients as well as basic science studies were included for these two topics. This review found that transgender patients on GAHT have an elevated fracture risk, but GAHT has beneficial effects on bone mineral density in transgender women. Transgender women on GAHT also have an increased risk of venous thromboembolism, stroke and myocardial infarction compared with cisgender women. Despite these elevated risks, studies have found it is safe to continue GAHT perioperatively for both transgender women and men undergoing low-risk operations. Orthopaedic and sports medicine clinicians should understand these unique health considerations for equitable patient care.

Despite regular gender-affirming hormone therapy (GAHT), the presence of uterine bleeding can occur occasionally and cause profound discomfort. This study aimed to evaluate the histologic features and immunohistochemical expression of estrogen (ER), progesterone (PR), and androgen receptors (AR) in the endometrium and myometrium of transgender men receiving testosterone therapy and relate them to clinical and hormonal characteristics.

Retrospective cross-sectional study.

Thirty-four transgender men undergoing gender-affirming surgery were included. Clinical, sociodemographic, and laboratory data as well as anatomopathological and immunohistochemical findings were evaluated.

The participants' mean age was 42.35 (SD, 10.00) years, and body mass index was 28.16 (SD, 5.52) kg/m2. The mean GAHT duration before surgery was 5.36 (SD, 3.24) years. The mean testosterone levels were 814.98 (SD, 407.13) ng/dL, and estradiol levels were 55.22 (SD, 25.27) pg/mL. The endometrium was atrophic in 61.8%, proliferative in 17.6%, and secretory in 20.6%. Immunohistochemical receptor analysis revealed that endometrial epithelial cells expressed ER (90%) and PR (80%), with a lower expression of AR (30%). In stromal tissue, the median ER, PR, and AR expression was lower than that in the epithelium (60%, 70%, and 25%, respectively). The myometrium showed high expression of PR (90%) and ER (70%), with the highest expression of AR (65%) being localized to this region.

In the present study, GAHT induced an atrophic condition of the endometrium in two-thirds of the transgender men, with a limited AR expression in the endometrial region. The present results suggest that testosterone-based GAHT for a mean of 5 years is safe in transgender men achieving amenorrhea.

Transgender adolescents can undergo puberty suppression (PS) and subsequent gender-affirming hormone therapy (GAHT) but little information is available on the expected rate of physical changes.

To investigate the time course of body composition changes during PS and GAHT.

In this study, retrospective data of 380 trans boys and 168 trans girls treated with PS prior to GAHT from a gender identity clinic were included. Total lean and fat mass Z-scores using birth-assigned sex as reference were determined using dual-energy X-ray absorptiometry.

In trans boys, lean mass Z-scores decreased (-0.32, 95% CI -0.41; -0.23) and fat mass Z-scores increased (0.31, 95% CI 0.21; 0.41) in the first year of PS and remained stable thereafter. Lean mass Z-scores increased (0.92, 95% CI 0.81; 1.04) and fat mass Z-scores decreased (-0.43, 95% CI -0.57; -0.29) only during the first year of testosterone,. In trans girls, both lean and fat mass Z-scores gradually changed over 3 years of PS (respectively -1.13, 95% CI -1.29; -0.98 and 1.06, 95% CI 0.90; 1.23). In the first year of GAHT, lean mass Z-scores decreased (-0.19, 95% CI -0.36; -0.03) while fat mass Z-scores remained unchanged after 3 years (-0.02, 95% CI -0.20; 0.16).

Compared with peers, trans girls experienced ongoing lean mass decrease and fat mass increase during 3 years of PS while in trans boys smaller changes were observed that stabilized after 1 year. A large increase in lean mass Z-scores occurred only during the first year of testosterone treatment. In trans girls, body composition changed only slightly during GAHT. This information can improve counseling about treatment effects.

For some patients, feminine facial features may cause significant gender dysphoria. Multiple nonsurgical and surgical techniques exist to masculinize facial features. Nonsurgical techniques include testosterone supplementation and dermal fillers. Surgical techniques include soft tissue manipulation, synthetic implants, regenerative scaffolding, or bony reconstruction. Many techniques are derived from experience with cisgender patients, but are adapted with special considerations to differing anatomy between cisgender and transgender men and women. Currently, facial masculinization is less commonly sought than feminization, but demand is likely to increase as techniques are refined and made available.

Knowledge regarding the effects and side effects of gender-affirming hormone therapy (GAHT) in adults is rapidly growing, partly through international research networks such as the European Network for the Investigation of Gender Incongruence (ENIGI). However, data on the effects of puberty suppression (PS) and GAHT in transgender and gender diverse (TGD) youth are limited, although these data are of crucial importance, given the controversies surrounding this treatment.

We sought to present a detailed overview of the design of the ENIGI Adolescents study protocol, including the first baseline data.

The ENIGI Adolescents study is an ongoing multicenter prospective cohort study. This study protocol was developed by 3 European centers that provide endocrine care for TGD adolescents and were already part of the ENIGI collaboration: Amsterdam, Ghent, and Florence.

Study outcomes include physical effects and side effects, laboratory parameters, bone mineral density, anthropometric characteristics, attitudes toward fertility and fertility preservation, and psychological well-being, which are measured in the study participants during PS and GAHT, up to 3 years after the start of GAHT.

Between November 2021 and May 2023, 172 TGD adolescents were included in the ENIGI Adolescents protocol, of whom 51 were assigned male at birth (AMAB) and 121 were assigned female at birth (AFAB); 3 AFAB participants reported a nonbinary gender identification. A total of 76 participants were included at the start of PS, at a median (IQR) age of 13.7 (12.9-16.5) years in AMAB and 13.5 (12.4-16.1) years in AFAB individuals. The remaining 96 participants were included at start of GAHT, at a median (IQR) age of 15.9 (15.1-17.4) years in AFAB and 16.0 (15.1-16.8) years in AMAB individuals. At the time of this report the study was open for inclusion and follow-up measurements were ongoing.

In response to the rising demand for gender-affirming treatment among TGD youth, this ongoing study is fulfilling the need for prospective data on the effects and safety of PS and GAHT, thus providing a foundation for evidence-based healthcare decisions.

This study has a strong multicenter, prospective design that allows for systematic data collection. The use of clinical and self-reported data offers a broad range of outcomes to evaluate. Nevertheless, the burden of additional measurements and questionnaires may lead to withdrawal or lower response rates. Few participants with a non-binary gender identity have been included.

With the ENIGI Adolescents study we aim to create a comprehensive dataset that we can use for a wide range of studies to address current controversies and uncertainties and to improve healthcare for TGD adolescents.

Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity).

Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ).

14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p = 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p < 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people.

Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.

While endocrinologists continue to initiate gender-affirming hormone therapy (GAHT) in healthy transgender and gender diverse (TGD) patients, they may also encounter more TGD patients in their clinics with complex medical histories that influence the patient-provider shared decision-making process for initiating or continuing GAHT. The purpose of this Approach to the Patient article is to describe management considerations in 2 adults with thromboembolic disease and 2 adults with low bone mineral density in the setting of feminizing and masculinizing GAHT.

The inclusion of transgender people in elite sport has been a topic of debate. This narrative review examines the impact of gender-affirming hormone therapy (GAHT) on physical performance, muscle strength, and markers of endurance.

MEDLINE and Embase were searched using terms to define the population (transgender), intervention (GAHT), and physical performance outcomes.

Existing literature comprises cross-sectional or small uncontrolled longitudinal studies of short duration. In nonathletic trans men starting testosterone therapy, within 1 year, muscle mass and strength increased and, by 3 years, physical performance (push-ups, sit-ups, run time) improved to the level of cisgender men. In nonathletic trans women, feminizing hormone therapy increased fat mass by approximately 30% and decreased muscle mass by approximately 5% after 12 months, and steadily declined beyond 3 years. While absolute lean mass remains higher in trans women, relative percentage lean mass and fat mass (and muscle strength corrected for lean mass), hemoglobin, and VO2 peak corrected for weight was no different to cisgender women. After 2 years of GAHT, no advantage was observed for physical performance measured by running time or in trans women. By 4 years, there was no advantage in sit-ups. While push-up performance declined in trans women, a statistical advantage remained relative to cisgender women.

Limited evidence suggests that physical performance of nonathletic trans people who have undergone GAHT for at least 2 years approaches that of cisgender controls. Further controlled longitudinal research is needed in trans athletes and nonathletes.

To summarise the evidence regarding the effects of gender-affirming hormone therapy (GAHT) on bone health in transgender people, to identify key knowledge gaps and how these gaps can be addressed using preclinical rodent models.

Sex hormones play a critical role in bone physiology, yet there is a paucity of research regarding the effects of GAHT on bone microstructure and fracture risk in transgender individuals. The controlled clinical studies required to yield fracture data are unethical to conduct making clinically translatable preclinical research of the utmost importance. Novel genetic and surgical preclinical models have yielded significant mechanistic insight into the roles of sex steroids on skeletal integrity. Preclinical models of GAHT have the potential inform clinical approaches to preserve skeletal integrity and prevent fractures in transgender people undergoing GAHT. This review highlights the key considerations required to ensure the information gained from preclinical models of GAHT are informative.

Gender-affirming testosterone therapy is increasingly prescribed among transmasculine adolescents and has been associated with improved mental health outcomes. However, expected and perceived effects of testosterone have not previously been compared in this population.

We compared desired and reported effects of testosterone in all consecutive transmasculine adolescents followed at a large interdisciplinary gender diversity clinic in North America. Participants received a prescription for testosterone and were first seen between November 2016 and May 2021. Our study was a retrospective audit of case notes. We collected self-reported desired effects prior to initiation of testosterone and self-reported perceived effects from participants' medical records up to 24 months after initiation. The masculinizing effects of testosterone considered in our study were increased body/facial hair, voice deepening/Adam's apple growth, increased muscle mass, clitoromegaly, and body fat redistribution.

There were 76 participants included in this study. Mean age at prescription of testosterone was 16.31 years (standard deviation: 0.99 years). The effects desired by the greatest proportion of participants prior to initiation were increased body/facial hair (69 %) and voice deepening/Adam's apple growth (52 %). These same two effects were the most reported by participants, reaching 80 % report rates at 12 months, and increasing steadily across the 24-month follow-up period.

Our study shows that for most, but not all gender diverse adolescents undergoing testosterone therapy, the most expected physical changes were seen in the first year of gender-affirming treatment. More research and provider education are needed to offer optimal counseling for adolescents undergoing gender-affirming hormone therapy.

Gender diverse adolescents have low pretreatment bone mineral density (BMD), with variable changes in BMD after initiation of gender-affirming treatment. We aimed to assess factors associated with low BMD in gender diverse youth. Sixty-four patients were included in our analysis (73% assigned male at birth). Subtotal whole-body BMD Z-scores were low in 30% of patients, and total lumbar spine BMD Z-scores low in 14%. There was a positive association with body mass index, and no association with vitamin D level. Male sex assigned at birth was associated with lower pretreatment BMD, with lower average BMD Z-scores compared to previous studies.

Debate has surrounded whether the participation of trans women in female sporting categories is fair, specifically the retained male physiological advantage due to increased testosterone compared to cisgender females. Recently, individual sporting organisations have been investigating and assessing policies regarding trans women athlete participation in female categories, resulting in several banning participation. This review aims to discuss the scientific evidence and provide appropriate guidance for the inclusion of trans women in elite competitive female fencing categories. Fencing is an intermittent sport, where competitions can span 1 to 3 days. The lunge is the most common movement used to attack opponents, where a successful hit relies on the speed of the action. Male puberty induced increased circulating testosterone promotes a greater stature, cardiovascular function, muscle mass, and strength compared to cisgender females, culminating in a ~12-40% sport performance advantage. Elite cisgender male fencers perform significantly higher, ~17-30%, jump heights and leg power measures compared to elite cisgender female fencers, resulting in faster lunges. Trans women receiving androgen-suppression therapy for 12 months showed significant reductions in strength, lean body mass, and muscle surface area, but even after 36 months, the measurements of these three indices remained above those for cisgender females. Previous male muscle mass and strength can be retained through continuation of resistance training. The literature reviewed shows that there is a retained physiological advantage for trans women who have undergone male puberty when participating in the elite competitive female fencing category. A proposed solution of an open or third gender category for elite fencing competition promotes fair competition, while allowing trans women to compete in their chosen sport.

Many transgender (trans) individuals utilize gender-affirming hormone therapy (GAHT) to promote changes in secondary sex characteristics to affirm their gender. Participation rates of trans people in sport are exceedingly low, yet given high rates of depression and increased cardiovascular risk, the potential benefits of sports participation are great. In this review, we provide an overview of the evidence surrounding the effects of GAHT on multiple performance-related phenotypes, as well as current limitations. Whilst data is clear that there are differences between males and females, there is a lack of quality evidence assessing the impact of GAHT on athletic performance. Twelve months of GAHT leads to testosterone concentrations that align with reference ranges of the affirmed gender. Feminizing GAHT in trans women increases fat mass and decreases lean mass, with opposite effects observed in trans men with masculinizing GAHT. In trans men, an increase in muscle strength and athletic performance is observed. In trans women, muscle strength is shown to decrease or not change following 12 months of GAHT. Haemoglobin, a measure of oxygen transport, changes to that of the affirmed gender within 6 months of GAHT, with very limited data to suggest possible reductions in maximal oxygen uptake as a result of feminizing GAHT. Current limitations of this field include a lack of long-term studies, adequate group comparisons and adjustment for confounding factors (e.g. height and lean body mass), and small sample sizes. There also remains limited data on endurance, cardiac or respiratory function, with further longitudinal studies on GAHT needed to address current limitations and provide more robust data to inform inclusive and fair sporting programmes, policies and guidelines.

As the number of transgender and gender-diverse (TGD) people accessing gender-affirming care increases, the need for healthcare professionals (HCPs) providing gender-affirming hormonal therapy (GAHT) also increases. This chapter provides an overview of the HCPs interested in getting involved in providing GAHT.

Significant differences exist between feminine and masculine lower extremities, and this region contributes to gender dysphoria in transgender and nonbinary individuals.

A systematic review was conducted for primary literature on lower extremity (LE) gender affirmation techniques as well as anthropometric differences between male and female lower extremities, which could guide surgical planning. Multiple databases were searched for articles before June 2, 2021 using Medical Subject Headings. Data on techniques, outcomes, complications, and anthropometrics were collected.

A total of 852 unique articles were identified: 17 met criteria for male and female anthropometrics and 1 met criteria for LE surgical techniques potentially applicable to gender affirmation. None met criteria for LE gender affirmation techniques specifically. Therefore, this review was expanded to discuss surgical techniques for the LE, targeting masculine and feminine anthropometric ideals. LE masculinization can target feminine qualities, such as mid-lateral gluteal fullness and excess subcutaneous fat in the thigh and hips. Feminization can target masculine qualities like a low waist-to-hip ratio, mid-lateral gluteal concavity, calf hypertrophy, and body hair. Cultural differences and patient body habitus, which influence what is considered "ideal" for both sexes, should be discussed. Applicable techniques include hormone therapy, lipo-contouring, fat grafting, implant placement, and botulinum toxin injection, among others.

Due to lack of existing outcomes-based literature, gender affirmation of the lower extremities will rely on application of an array of existing plastic surgery techniques. However, quality outcomes data for these procedures is required to determine best practices.

Gender dysphoria is characterised by a sense of distress because of discordance between the self-perception of gender identity and the assigned sex. Hormonal treatment of transgender males uses testosterone to induce and preserve masculinisation.

The study investigated the safety of testosterone therapy in transgender males.

The present study used a retrospective file review of transgender male subjects who were treated with testosterone (initially transdermal testosterone gel and subsequently parenteral testosterone undecanoate) for at least 18 months and had subsequently achieved a serum testosterone level within the normal range of cisgender male counterparts. Changes in somatometric data and blood biomarkers were investigated.

The mean testosterone serum levels after approximately 18 months of treatment were about 545 ng/dL (SD ± 94 ng/dL). There was a statistically significant rise in body mass index (𝜒d = +1.23 kg/m2) with a reduction in blood glucose (𝜒d = -5.33 mg/dL) as well as statistically significant increases in aspartate transaminase (𝜒d = +4.3 U/L), haemoglobin (𝜒d = +1.72 g/dL), and haematocrit (𝜒d = +4.76%). In contrast, there were no significant changes in the lipidaemic profile of the subjects.

Treatment with testosterone is routinely used for the promotion of virilising physical changes in transgender males. However, the likelihood of adverse effects of continuous treatment is still unclear. This study contributed to the notion that achieving testosterone levels within the target range is a prerequisite for the safety of the gender-affirming treatment.

Sex-differences in high sensitivity troponin (hs-Tn) concentrations are well established. There is, however, limited data to guide interpretation of hs-Tn in transgender patients, particularly those receiving gender-affirming hormone therapy. Our purpose was to evaluate troponin testing in transgender patients.

Transgender adults attending a routine clinic visit provided demographic data, medical history, and venous blood samples. Patients with congestive heart failure or chronic kidney disease were excluded. hs-Tn was measured using the Architect Stat High Sensitivity Troponin-I (Abbott), Access 2 hsTnI (Beckman Coulter), and Elecsys Troponin T Gen 5 STAT (Roche) assays. hs-Tn below the limit of detection (LOD) is reported as the lower limit of detection (LLOD) RESULTS: Of 63 subjects, 76 % were transgender women. We found no significant difference in median hs-Tn concentrations or proportions of hs-Tn > LOD.

In this cohort of stable transgender patients without CHF or CKD, we did not observe differences in hs-Tn concentrations between transgender women and transgender men. Meaningful conclusions are limited owing to inadequate sample size and population differences. Further research on hs-troponin concentrations in this underrepresented, vulnerable population is needed.

Gender-affirming hormone therapy (GAHT) is prescribed to produce secondary sex characteristics aligning external anatomy with gender identity to mitigate gender dysphoria. Transgender women are generally treated with oestrogens and anti-androgens, whereas transgender men are treated with testosterone. The objective of this narrative review was to characterise the influence of GAHT on body composition and bone health in the transgender population to help address weight concerns and chronic disease risk.

Studies were extracted from PubMed and Scopus and limited to only those utilising imaging technologies for precise adipose tissue, lean mass, and bone mineral density (BMD) quantification.

Although methodologies differed across the 20 investigations that qualified for inclusion, clear relationships emerged. Specifically, among transgender women, most studies supported associations between oestrogen therapy and decreases in lean mass and increases in both, fat mass and body mass index (BMI). Within transgender men, all studies reported associations between testosterone therapy and increases in lean mass, and although not as consistent, increases in BMI and decreases in fat mass. No consistent changes in BMD noted for either group.

Additional research is needed to appropriately assess and evaluate the implications of these body composition changes over time (beyond 1 year) in larger, more diverse groups across all BMI categories. Future studies should also seek to evaluate nutrient intake, energy expenditure and other important lifestyle habits to diminish health disparities within this vulnerable population. Policies are needed to help integrate registered dietitians into the routine care of transgender individuals.

Transgender and gender diverse (TGD) individuals are at increased risk for the development of eating disorders, but very little has been published with regards to the unique aspects of their medical care in eating disorder treatment. Providing gender affirming care is a critical component of culturally competent eating disorder treatment. This includes knowledge of gender affirming medical and surgical interventions and how such interventions may be impacted by eating disordered behaviors, as well as the role of such interventions in eating disorder treatment and recovery. TGD individuals face barriers to care, and one of these can be provider knowledge. By better understanding these needs, clinicians can actively reduce barriers and ensure TGD individuals are provided with appropriate care. This review synthesizes the available literature regarding the medical care of TGD patients and those of patients with eating disorders and highlights areas for further research.

The transmasculine and gender diverse (TMGD) spectrum includes transgender men and non-binary individuals whose sex was assigned female at birth. Many TMGD patients pursue treatment with exogenous testosterone to acquire masculine characteristics. Some may choose to undergo gynecological gender-affirming surgery for total hysterectomy with bilateral salpingectomy and/or bilateral oophorectomy (TH/BSO). The decision to retain or remove the ovaries in the setting of chronic testosterone therapy has implications on reproductive health, oncologic risk, endocrine management, cardiovascular health, bone density and neurocognitive status. However, there is limited evidence on the long-term outcomes from this intervention.

Here we review health-related outcomes of oophorectomy in TMGD population treated with chronic testosterone therapy in order to guide clinicians and patients in the decision to retain or remove their ovaries.

We conducted a systematic literature review following PRISMA guidelines. MEDLINE, EMBASE, ClinicalTrials.gov, and Cochrane Library databases were searched for peer-reviewed studies published prior to October 26, 2021 that: (i) included transgender men/TMGD individuals in the study populations; (ii) were full-text randomized controlled studies, case reports, case series, retrospective cohort studies, prospective cohort studies, qualitative studies, and cross-sectional studies; and (iii) specifically discussed ovaries, hysterectomy, oophorectomy, ovariectomy, or gonadectomy.

We identified 469 studies, of which 39 met our inclusion criteria for this review. Three studies discussed fertility outcomes, 11 assessed histopathological changes to the ovaries, 6 discussed ovarian oncological outcomes, 8 addressed endocrine considerations, 3 discussed cardiovascular health outcomes, and 8 discussed bone density. No studies were found that examined surgical outcomes or neurocognitive changes.

There is little information to guide TMGD individuals who are considering TH/BSO versus TH/BS with ovarian retention. Our review suggests that there is limited evidence to suggest that fertility preservation is successful after TH/BS with ovarian retention. Current evidence does not support regular reduction in testosterone dosing following oophorectomy. Estradiol levels are likely higher in individuals that choose ovarian retention, but this has not been clearly demonstrated. Although bone mineral density decreases following oophorectomy, data demonstrating an increased fracture risk are lacking. No studies have described the specific impact on neurocognitive function, or changes in operative complications. Further research evaluating long-term health outcomes of oophorectomy for TMGD individuals treated with chronic testosterone therapy is warranted to provide comprehensive, evidence-based healthcare to this patient population. Sahil Kumar, Smita Mukherjee, Cormac O'Dwyer, et al. Health Outcomes Associated With Having an Oophorectomy Versus Retaining One's Ovaries for Transmasculine and Gender Diverse Individuals Treated With Testosterone Therapy: A Systematic Review. Sex Med Rev 2022;10:636-647.

Women during pregnancy and postpartum show high rates of obesity and metabolic diseases, especially women with excessive caloric intake. In the past, it was proved that individuals with high intrinsic aerobic exercise capacities showed higher lipid metabolism and lower fat production than those with low intrinsic aerobic exercise capacities. The purpose of this study was to determine whether mice with the low-fitness phenotype (LAEC) were more likely to develop metabolic abnormalities and obesity under dietary induction after delivery, and if mice with a high-fitness phenotype (HAEC) had a protective mechanism. After parturition and weaning, postpartum Institute of Cancer Research (ICR) mice received dietary induction for 12 weeks and were divided into four groups (n = 8 per group): high-exercise capacity postpartum mice with a normal chow diet (HAEC-ND); high-exercise capacity postpartum mice with a high-fat diet (HAEC-HFD); low-exercise capacity postpartum mice with a normal chow diet (LAEC-ND); and low-exercise capacity postpartum mice with a high-fat diet (LAEC-HFD). Obesity caused by a high-fat diet led to decreased exercise performance (p < 0.05). Although there were significant differences in body posture under congenital conditions, the LAEC mice gained more weight and body fat after high-fat-diet intake (p < 0.05). Compared with HAEC-HFD, LAEC-HFD significantly increased blood lipids, such as total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein (LDL) and other parameters (p < 0.05), and the content of TG in the liver, as well as inducing poor glucose tolerance (p < 0.05). In addition, after HFD intake, excessive energy significantly increased glycogen storage (p < 0.05), but the LAEC mice showed significantly lower muscle glycogen storage (p < 0.05). In conclusion, although we observed significant differences in intrinsic exercise capacity, and body posture and metabolic ability were also different, high-fat-diet intake caused weight gain and a risk of metabolic disorders, especially in postpartum low-fitness mice. However, HAEC mice still showed better lipid metabolism and protection mechanisms. Conversely, LAEC mice might accumulate more fat and develop metabolic diseases compared with their normal rodent chow diet (ND) control counterparts.

Background: Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8. Aim: The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment. Methods: The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings. Results: A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health. Conclusions: The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person.