Thrombotic risk associated with gender-affirming hormone therapy.

Transgender and gender-expansive (TG) people-those who identify with a gender other than their assigned sex at birth-frequently experience gender dysphoria, which is associated with negative health outcomes. One key strategy for improving gender dysphoria is the use of gender-affirming hormone therapy (GAHT): estrogen for feminization and testosterone for masculinization. Estrogen use in cisgender women is associated with well-established changes in hemostatic parameters, including increases in prothrombotic factors and decreases in inhibitors of coagulation. Cisgender women using estrogen have an increased risk of thrombosis. Studies of thrombosis risk associated with estrogen GAHT in TG people are less robust, with some studies limited by the use of hormones and hormone management strategies that are no longer recommended. However, TG women using estrogen appear to be at increased risk of both arterial and venous thrombosis, which may increase with longer time on estrogen. Testosterone use in both cisgender and transgender men is associated with increases in hemoglobin and hematocrit, which can lead to erythrocytosis and thus increased risk of thrombosis. The results of studies evaluating thrombosis risk in the setting of testosterone use are mixed. This review presents an overview of alterations in hemostatic parameters and thrombosis risk associated with use of exogenous estrogen and testosterone. Understanding what is known and unknown about thrombosis risk associated with use of these hormones is essential for hematologists who may be asked to evaluate TG people and provide guidance on management of those who may be at increased risk of thrombosis.

Clinicians in the Veterans Health Administration initiate gender-affirming hormone therapy in concordance with clinical guideline recommendations.

Background: Gender-affirming hormone therapy (GAHT) is a common medical intervention sought by transgender and gender diverse (TGD) individuals. Initiating GAHT in accordance with clinical guideline recommendations ensures delivery of high-quality care. However, no prior studies have examined how current GAHT initiation compares to recommended GAHT initiation. Objective: This study assessed guideline concordance around feminizing and masculinizing GAHT initiation in the Veterans Health Administration (VHA). Methods: The sample included 4,676 veterans with a gender identity disorder diagnosis who initiated feminizing (n=3,547) and masculinizing (n=1,129) GAHT between 2007 and 2018 in VHA. Demographics and health conditions on veterans receiving feminizing and masculinizing GAHT were assessed. Proportion of guideline concordant veterans on six VHA guidelines on feminizing and masculinizing GAHT initiation were determined. Results: Compared to veterans receiving masculinizing GAHT, a higher proportion of veterans receiving feminizing GAHT were older (≥60 years: 23.7% vs. 6.3%), White non-Hispanic (83.5% vs. 57.6%), and had a higher number of comorbidities (≥7: 14.0% vs. 10.6%). A higher proportion of veterans receiving masculinizing GAHT were Black non-Hispanic (21.5% vs. 3.5%), had posttraumatic stress disorder (43.0% vs. 33.9%) and positive military sexual trauma (33.5% vs.16.8%; all p-values<0.001) than veterans receiving feminizing GAHT. Among veterans who started feminizing GAHT with estrogen, 97.0% were guideline concordant due to no documentation of contraindication, including venous thromboembolism, breast cancer, stroke, or myocardial infarction. Among veterans who started spironolactone as part of feminizing GAHT, 98.1% were guideline concordant as they had no documentation of contraindication, including hyperkalemia or acute renal failure. Among veterans starting masculinizing GAHT, 90.1% were guideline concordant due to no documentation of contraindications, such as breast or prostate cancer. Hematocrit had been measured in 91.8% of veterans before initiating masculinizing GAHT, with 96.5% not having an elevated hematocrit (>50%) prior to starting masculinizing GAHT. Among veterans initiating feminizing and masculinizing GAHT, 91.2% had documentation of a gender identity disorder diagnosis prior to GAHT initiation. Conclusion: We observed high concordance between current GAHT initiation practices in VHA and guidelines, particularly for feminizing GAHT. Findings suggest that VHA clinicians are initiating feminizing GAHT in concordance with clinical guidelines. Future work should assess guideline concordance on monitoring and management of GAHT in VHA.

Effects of gender-affirming hormone therapy on body fat: a retrospective case‒control study in Chinese transwomen.

BACKGROUND: There is insufficient research on how gender-affirming hormone therapy (GAHT) affects body fat modifications in transwomen from China. It is unclear whether hormone therapy affects the prevalence of obesity and blood lipid levels within this population. The current research aimed to assess how GAHT and treatment duration had an impact on the change in and redistribution of body fat in Chinese transwomen. METHODS: This study included 40 transwomen who had not received GAHT and 59 who had. Body fat, blood lipid, and blood glucose levels were measured. GAHT is mainly a pharmacologic (estrogen and anti-androgen) treatment. The study also stratified participants based on the duration of GAHT to assess its impact on body fat distribution. The duration of GAHT was within one year, one to two years, two to three years, or more than three years. RESULTS: After receiving GAHT, total body fat increased by 19.65%, and the percentage of body fat increased by 17.63%. The arm, corrected leg, and leg regions showed significant increases in fat content (+ 24.02%, + 50.69%, and + 41.47%, respectively) and percentage (+ 25.19%, + 34.90%, and + 30.39%, respectively). The total visceral fat content decreased (-37.49%). Based on the diagnostic standards for a body mass index ≥ 28 or total body fat percentage ≥ 25% or 30%, the chance of developing obesity did not change significantly. Blood glucose levels significantly increased (+ 12.31%). Total cholesterol levels (-10.45%) decreased significantly. Fat changes in those who received GAHT for one to two years were significantly different from those who did not receive GAHT. CONCLUSION: After receiving GAHT, total body fat and regional fat increased in Chinese transwomen, and the body fat distribution changed from masculine to feminine, especially during the first two years. However, neither the increase in total body fat percentage nor the decrease in visceral fat content didn't bring about significant changes in the incidence of obesity, nor did triglycerides or low-density lipoprotein-cholesterol.

Laboratory Changes During Gender-Affirming Hormone Therapy in Transgender Adolescents.

OBJECTIVES: Guidelines for monitoring of medications frequently used in the gender-affirming care of transgender and gender-diverse (TGD) adolescents are based on studies in adults or other medical conditions. In this study, we aimed to investigate commonly screened laboratory measurements in TGD adolescents receiving gender-affirming hormone therapy (GAHT). METHODS: TGD adolescents were recruited from 4 study sites in the United States before beginning GAHT. Hemoglobin, hematocrit, hemoglobin A1c, alanine transaminase, aspartate aminotransferase, prolactin, and potassium were abstracted from the medical record at baseline and at 6, 12, and 24 months after starting GAHT. RESULTS: Two-hundred and ninety-three participants (68% designated female at birth) with no previous history of gonadotropin-releasing hormone analog use were included in the analysis. Hemoglobin and hematocrit decreased in adolescents prescribed estradiol (-1.4 mg/dL and -3.6%, respectively) and increased in adolescents prescribed testosterone (+1.0 mg/dL and +3.9%) by 6 months after GAHT initiation. Thirteen (6.5%) participants prescribed testosterone had hematocrit > 50% during GAHT. There were no differences in hemoglobin A1c, alanine transaminase, or aspartate aminotransferase. There was a small increase in prolactin after 6 months of estradiol therapy in transfeminine adolescents. Hyperkalemia in transfeminine adolescents taking spironolactone was infrequent and transient if present. CONCLUSIONS: Abnormal laboratory results are rare in TGD adolescents prescribed GAHT and, if present, occur within 6 months of GAHT initiation. Future guidelines may not require routine screening of these laboratory parameters beyond 6 months of GAHT in otherwise healthy TGD adolescents.

Difficulties of gender affirming treatment in trans women with BRCA1+ mutation: A case report.

Gender affirming treatment in transgender women is based on a combination of antiandrogens and estrogens, with the latter maintained over the long term. When prescribing these treatments, we must consider the possibility of developing estrogen-dependent breast cancer. In transgender women, a breast cancer incidence of 4.1 per 100,000 has been estimated, which would increase the risk by 46% in relation to cisgender men but decrease it by 70% in relation to cisgender women. It is known that certain gene mutations such as BRCA1 imply an increased risk of breast cancer, but at present the risk in transgender women with BRCA1 treated with estrogens is not well established. We present the case of a transgender woman with a family history of breast cancer and BRCA1 mutation and the therapeutic decisions made in a multidisciplinary team. Following this case, we review and discuss the published literature.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Most TGD patients achieve target testosterone levels within 9 months of GAHT initiation. Adverse effects of GAHT are rare, and are usually mild.

Persistent vaginal bleeding during gender-affirming hormone therapy in transgender men.

PURPOSE: While it is common for menstrual cycles to cease within the initial 6 months of treatment, there are instances where some transgender men may not experience this cessation. We analyzed transgender men undergoing gender-affirming hormone therapy (GAHT) with testosterone who experienced breakthrough bleeding in order to identify the factors associated with this condition. METHODS: In this case-control study, 24 transgender men in the case group and 48 in the control group were assessed for clinical, sociodemographic, hormonal, and body composition variables using dual-energy X-ray absorptiometry. All participants had been on GATH for at least 6 months. RESULTS: A few transgender men experienced persistent breakthrough bleeding, which was associated with decreased testosterone levels and free androgen index (FAI) compared with controls (p = 0.002 and p = 0.008, respectively). Among individuals with breakthrough bleeding, 50% had testosterone levels below the lowest tertile calculated for the sample, compared with 18.8% on controls (p = 0.007). After therapy adjustment, testosterone levels increased compared with the values obtained in the initial bleeding episode (p = 0.031). Eight transgender men required the addition of an oral progestogen to achieve amenorrhea, and these individuals had higher BMI than those in whom the adjustment of the parenteral testosterone dose was adequate (p = 0.026). A univariate prevalence ratio analysis revealed a negative association of persistent bleeding with testosterone levels (p = 0.028) and FAI levels (p = 0.019). CONCLUSION: Higher BMI and lower levels of testosterone and FAI were the main factors associated with breakthrough bleeding in transgender men.

Bone health and body composition in transgender adults before gender-affirming hormonal therapy: data from the COMET study.

PURPOSE: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.

The Impact of Gender-Affirming Hormone Therapy on Physical Performance.

CONTEXT: 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. EVIDENCE ACQUISITION: MEDLINE and Embase were searched using terms to define the population (transgender), intervention (GAHT), and physical performance outcomes. EVIDENCE SYNTHESIS: 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. CONCLUSION: 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.

Back to the Future: Is GnRHa Treatment in Transgender and Gender Diverse Adolescents Only an Extended Evaluation Phase?

CONTEXT: The role of body modifications induced by gonadal suppression in transgender and gender diverse adolescents on psychological functioning has not yet been evaluated. OBJECTIVE: The main aim of the present study was to explore several hormone, physical and psychological functioning changes during gonadotropin-releasing hormone analog (GnRHa) treatment in transgender and gender diverse adolescents (TGDAs). The potential relationship between the physical and hormone effects of GnRHa and psychological well-being, along with its magnitude, was assessed for the first time. METHODS: This prospective multidisciplinary study included 36 TGDA (22 assigned female at birth, and 14 assigned male at birth) who received psychological assessment followed by triptorelin prescription after referring to the Florence Gender Clinic. This study consisted of 3 time points: first referral (T0), psychological assessment (T1); and treatment with intramuscular injections of triptorelin for 3 up to 12 months (T2). Psychometric questionnaires were administered at each time point, and clinical and biochemical evaluations were performed at T1 and T2. RESULTS: The following results were found: (1) GnRHa showed efficacy in inhibiting puberty progression in TGDAs; (2) an increase in psychopathology was observed before starting GnRHa (T1) compared with baseline levels; (3) during GnRHa treatment (T2), a significant improvement in psychological functioning, as well as decrease in suicidality, body uneasiness, depression, and anxiety levels were observed; (4) hormone and physical changes (in terms of gonadotropin and sex steroid levels, height and body mass index percentiles, waist-hip ratio, and acne severity) observed during triptorelin treatment significantly correlated with a reduction in suicidal ideation, anxiety, and body image concerns. CONCLUSION: Psychological improvement in TGDA on GnRHa seems to be related to the objective body changes induced by a GnRHa. Therefore, the rationale for treatment with a GnRHa may not only be considered an extension of the evaluation phase, but also the start of a medical (even if reversible) gender-affirming path, especially in TGDAs whose puberty has already progressed.

Time Course of Body Composition Changes in Transgender Adolescents During Puberty Suppression and Sex Hormone Treatment.

CONTEXT: 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. OBJECTIVE: To investigate the time course of body composition changes during PS and GAHT. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

The influence of sex steroid treatment on insular connectivity in gender dysphoria.

BACKGROUND: Sex-specific differences in brain connectivity were found in various neuroimaging studies, though little is known about sex steroid effects on insular functioning. Based on well-characterized sex differences in emotion regulation, interoception and higher-level cognition, gender-dysphoric individuals receiving gender-affirming hormone therapy represent an interesting cohort to investigate how sex hormones might influence insular connectivity and related brain functions. METHODS: To analyze the potential effect of sex steroids on insular connectivity at rest, 11 transgender women, 14 transgender men, 20 cisgender women, and 11 cisgender men were recruited. All participants underwent two magnetic resonance imaging sessions involving resting-state acquisitions separated by a median time period of 4.5 months and also completed the Bermond-Vorst alexithymia questionnaire at the initial and final examination. Between scans, transgender subjects received gender-affirming hormone therapy. RESULTS: A seed based functional connectivity analysis revealed a significant 2-way interaction effect of group-by-time between right insula, cingulum, left middle frontal gyrus and left angular gyrus. Post-hoc tests demonstrated an increase in connectivity for transgender women when compared to cisgender men. Furthermore, spectral dynamic causal modelling showed reduced effective connectivity from the posterior cingulum and left angular gyrus to the left middle frontal gyrus as well as from the right insula to the left middle frontal gyrus. Alexithymia changes were found after gender-affirming hormone therapy for transgender women in both fantasizing and identifying. CONCLUSION: These findings suggest a considerable influence of estrogen administration and androgen suppression on brain networks implicated in interoception, own-body perception and higher-level cognition.

Implications of testosterone therapy on wound healing and operative outcomes of gender-affirming chest masculinization surgery.

The increased awareness of the transgender population and their medical needs has given rise to a wide array of gender-affirming surgeries and hormonal therapies. To better understand the implication of testosterone therapy on female-to-male gender-affirming mastectomies, we conducted a retrospective cohort study based on the medical histories of 170 transgender males operated on by a single surgeon over 18 years. One hundred and one (59.4%) patients received hormonal therapy. The average age of patients in the testosterone treatment group was 20.6 ± 5.3 (range 14-49) years. The median weight of resected breast tissue was 318 g (IQR 221-515) and 311.5 g (IQR 223-480) in patients treated with testosterone, compared to 380 g (IQR 225-735) and 370 g (IQR 240-700) in patients without testosterone treatment (for the right and left breast, respectively). Supplementary liposuction was performed in 35 patients, of whom 23 (64%) were treated with testosterone. Fifty-four patients (31.7%) experienced surgical complications, and 55.6% of complications were recorded in the group treated with testosterone. Forty-nine patients (28.8%) recorded their satisfaction using the Likert satisfaction scale; the average satisfaction was 4.86 ± 0.35 in the non-testosterone group and 4.63 ± 0.69 in the testosterone group. Opposing previous cohorts, we did not find a statistically significant association between testosterone and increased surgical complications in gender-affirming mastectomies. Possible explanations include our practice of avoiding testosterone therapy several weeks before the operation and vigorous hemostasis methods.

Endocrinological Approach to Adolescents with Gender Dysphoria: Experience of a Pediatric Endocrinology Department in a Tertiary Center in Turkey

Objective: A significant rise in the number of trans adolescents seeking medical interventions has been reported in recent years. The aim of this study was to report the clinical features, treatment, and follow-up of adolescents with gender dysphoria (GD) with our increased experience. Methods: Twenty-six male-to-female (MTF) and twenty-seven female-to-male (FTM) adolescents who were referred to the GD-outpatient clinic between 2016 and 2022 were reviewed. The clinical and laboratory findings of thirty transgender adolescents (15 FTM /15 MTF) who received medical intervention were evaluated retrospectively. Results: Most individuals (60.4%) were admitted between 2020 and 2022, and the remaining (39.6%) were admitted between 2016 and 2019. At the time of referral, median age was 16.3 years [interquartile range (IQR) 1.53; range 13.2-19.4] in 26 MTF, and 16.4 years (IQR 1.74; range 11.7-21.6) in 27 FTM adolescents. The median age at pubertal blockage with gonadotropin-releasing hormone analog and androgen receptor blocker was 16.4 years (IQR 1.4; range 11.7-17.8) in 22 adolescents (9 MTF, 13 FTM), and 17.4 years (IQR 1.4; range 15.5-19.4) in 6 MTF individuals, respectively. Cross-sex hormone therapy was commenced in 21 adolescents (12 MTF, 9 FTM) at the median age of 17.7 years (IQR 0.61; range 16-19.5). Fifteen individuals (8 MTF, 7 FTM) have been transferred to the adult endocrinology department in transition clinics. Conclusion: All treatments were generally well tolerated and effective, including bicalutamide, and no significant side effects were observed. Transition clinics played an important role in the better management of gender reassignment processes.

Changing trends in transgender demographics and morbidity: baseline data from a Spanish cohort.

The number of transgender people who request hormone treatment is increasing worldwide. We obtained base clinical and demographic information from transgender people treated at a specialised clinic in Spain (n =484) and studied changes over time. Transgender women treated in 2009-14 were older than those treated in 2015-20 (29years vs 17years), had a lower academic level and had higher anxiolytics consumption. Transgender men treated in 2009-14 were older than those treated later (27years vs 17years) and had a lower academic level. These trends reflect favourable changes in how the transgender population is treated by society and health services.

Gender identity: Current concepts and gender-affirming hormone therapy.

In the past five years, healthcare organisation for trans people in Spain has changed as laws intended to protect sexual and gender diversity have been put in place. As a result, endocrinologists are not only on the front lines (understood as prescribing and following up gender-affirming hormone therapy) but also coordinating multidisciplinary healthcare for these individuals. Advances in transgender medicine, the complexity of diverse trans identities and the impact of hormone therapy on quality of life and risk of middle- and long-term complications call for in-depth examination of a personalised biopsychosocial approach to trans people that requires specific training in this field of knowledge as well as updates on the concepts, terminology and drug treatments used.

The metabolic effects of hormonal treatment in transgender males: Safety of the testosterone gender-affirming therapy.

BACKGROUND: 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. OBJECTIVE: The study investigated the safety of testosterone therapy in transgender males. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.