BACKGROUND: In the last decade, healthcare for the transgender population has increased considerably in many countries thanks to depathologization movements and the easier accessibility of medical assistance. The age at which they request to start gender-affirming hormones (GAHs) is increasingly younger. The cardiovascular risk associated with hormonal treatment is a novel research field, and the published studies are heterogeneous and inconclusive. Our objective is to determine the metabolic impact of GAHs in the transgender people treated in our Gender Identity Treatment Unit.
METHODS: We designed a pre-post study to analyze changes in anthropometric parameters (weight and body mass index), analytical determinations (fasting blood glucose, glycated hemoglobin, and lipoproteins), and blood pressure control in the transgender population treated with GAHs in Puerta del Mar University Hospital. These variables were collected before and one year after hormonal therapy.
RESULTS: A total of 227 transgender people were recruited between 2017 and 2020, 97 (40.09%) transwomen and 136 (59.91%) transmen. The average age at which GAHs began was 18 years. Weight, body mass index, and blood pressure increased significantly in both genders. Transmen showed a more atherogenic lipid profile, with a decrease in cholesterol LDL (p < 0.001) and an increase in triglycerides (p < 0.001). The risk of developing prediabetes or diabetes did not increase one year after treatment, although non-specific alterations in carbohydrate metabolism were detected, such as an increase in glycated hemoglobin in transmen (p = 0.040) and fasting blood glucose in transwomen (p = 0.008). No thromboembolic processes or cardiovascular events were reported during the first year of treatment.
CONCLUSIONS: In our setting, transgender people developed changes in their metabolic profiles in the first year after hormonal treatment. Both transmen and transwomen showed early alterations in lipid and carbohydrate metabolism, slight elevations in blood pressure, and a tendency to gain weight. This makes lifestyle interventions necessary from the beginning of GAHs.

There is current scientific and legal controversy about sports competition eligibility regulations for transgender athletes. In this case study, we quantified performances by an elite, transgender woman (male sex, female gender identity) college swimmer who competed in both the men\'s and women\'s National Collegiate Athletic Association (NCAA) categories. We also contextualized her performances with respect to world-record performances and contemporary elite college swimmers. These data demonstrate that the declines in freestyle swimming performances of a transgender woman after about 2 yr of reported feminizing gender-affirming hormone treatment (0.5% for the 100 to 7.3% for the 1,650 yard distance) are smaller than the observed sex-related differences in performance of top 200 world record performances in metric distances of similar durations (11.4% for the 100 m to 9.3% for the 1,500 m distance). Despite slower performances, the transgender woman swimmer experienced improvements in performance for each freestyle event (100 to 1,650 yards) relative to sex-specific NCAA rankings, including producing the best swimming time in the NCAA for the 500-yard distance (65th in the men\'s category in 2018-2019 to 1st in the women\'s, 2022). Similarly, NCAA-ranked male swimmers had no improvements in rank in the men\'s category during the same time frame. Our findings suggest that the performance times of the transgender woman swimmer in the women\'s NCAA category were outliers for each event distance and suggest that the transgender woman swimmer had superior performances relative to rank-matched swimmers. Our analysis may be useful as a framework for regulators considering participation guidelines, which promote fair competition for all athletes-irrespective of gender identity.NEW & NOTEWORTHY This case study, longitudinal analysis of freestyle swimming performances before and after 2 yr of feminizing gender-affirming hormone therapy of an elite transgender woman (male sex, female gender identity), demonstrates superior performance relative to rank-matched female swimmers and a lower performance gap than previously observed between elite male and female swimmers.

The cognitive effects of cross-sex hormone therapy (CSHT) are not well understood. In cisgender individuals, sex hormone therapy can impact neurotransmitter levels and structural anatomy. Similarly, in gender-diverse persons, CSHT has been associated with neural adaptations, such as growth in brain structures resembling those observed in cisgender individuals of the same sex. Hormone-related changes in learning and memory, as seen in menopause, are associated with physiological hypogonadism or a decline in hormones, such as estradiol. The present study examined the effect of estradiol administration in humans on glutamate concentration in brain regions involved in semantic and working memory (i.e., the dorsolateral prefrontal cortex [DLPFC], the posterior hippocampus, and the pregenual anterior cingulate cortex) and its relationship with memory.
Eighteen trans women (male biological sex assigned at birth) ceased CSHT for 30 days for a washout phase (t1) upon study enrollment to reach a hypogonadal state. Working and semantic memory, cognition, hormonal assays, and brain imaging were assessed. Participants resumed CSHT for 60 days for a replacement phase (t2), after which the same evaluations from t1 were repeated.
Estradiol increased among trans women after 60 days of resumed CSHT with significant improvements in semantic memory compared to the hypogonadal phase. Working memory recall was significantly and positively correlated to glutamate in the DLPFC during the reinstatement phase, although the relationship was not moderated by levels of estradiol.
These results may have clinical implications for the therapeutic effects of estradiol replacement, serving as a protective factor against cognitive decline and impairment for trans women post-gonadectomy.

OBJECTIVE: The use of sex steroids by trans people has been of paramount importance regarding body changes during gender transition. The objective of this study was to assess the effects of an injectable steroid combination frequently used by transwomen, namely estradiol enanthate with dihydroxyprogesterone acetophenide (E2EN/DHPA), on blood pressure and metabolic outcomes using an animal model.
METHODS: Two-month-old male Wistar rats were orchiectomized or sham-operated and divided into groups: (1) Sham treated with sesame oil vehicle (SG), (2) sham treated with E2EN/DHPA (SP), (3) orchiectomized rats treated with vehicle (OG), and (4) orchiectomized rats treated with E2EN/DHPA (OP), with all groups treated every 10 days for 5 months. We evaluated systolic blood pressure (SBP), body weight (BW), abdominal circumference, nasoanal length (NAL), food and water intake (FI, WI), lipid profile (triglycerides, LDL, and HDL), serum C-reactive protein (CRP), plasma concentrations of urea (URpl) and creatinine (CRpl), 24 h urinary volume (V24 h), sodium and potassium excretion (UNa+, UK+), and proteinuria.
RESULTS: E2EN/DHPA administration reduced BW (SP 324.5 ± 31.1; OP 291.7 ± 41.3 g) and NAL (SP 24.5 ± 0.4; OP 24.6 ± 1.0 cm), without changing blood pressure, but increased URpl concentration (SP 55.0 ± 4.8; OP 42.5 ± 8.8 mg/dL) and CRpl (SP 0.47 ± 0.05; OP 0.46 ± 0.04 mg/dL), sodium (SP 3.1 ± 0.8; OP 3.3 ± 0.4 µEq/min/kg), potassium (SP 0.91 ± 0.22; OP 0.94 ± 0.22 µEq/min/kg) excretions and urinary volume (SP 15.5 ± 2.1; OP 16.4 ± 2.9 mL/24 h).
CONCLUSIONS: Cross-sex hormone therapy with E2EN/DHPA significantly modified body characteristics in male rats, producing a feminizing change without altering blood pressure or generating harmful metabolic parameters, but larger translational studies are still needed.

Background: Gender dysphoria is defined as a feeling of distress resulting from the incongruence between the sex assigned at birth and the gender identity, lasting longer than 6 months. In individuals with gender dysphoria, gender-affirming hormone therapy (GAHT) may improve quality of life (QoL). Objectives: We aimed to assess perceived QoL, to compare QoL scores between trans women and men and to identify possible contributing factors related to GAHT in a sample of transgender women and transgender men. Methods: In this cross-sectional study, transgender women and men were recruited by availability sampling from a national transgender health service. Individuals over 18 years old with a confirmed diagnosis of gender dysphoria receiving medically prescribed GAHT for at least 6 months were consecutively included. Also included were trans men who had undergone mastectomy and trans women who had received breast augmentation surgery. Individuals who had undergone gender affirmation surgery (specifically genital surgery) or with uncontrolled clinical/psychiatric conditions at the time of the initial assessment were excluded. Sociodemographic, physical, and hormone data were collected from all participants. The WHOQOL-BREF questionnaire was used to evaluate QoL. A total of 135 transgender individuals were invited. Seventeen individuals with previous genital surgery (12.6%) and five who refused to participate (3.7%) were excluded. Therefore, 113 patients were enrolled and completed the study (60 trans women and 53 trans men). Results: QoL scores did not differ between trans women and trans men. In trans women, greater breast development and stable relationships, and higher body mass index were associated with higher QoL domain scores. In trans men, higher domain scores were found in individuals in a stable relationship, with increased body hair, engaging in physical activity, and being employed. Conclusion: Data from this study suggest that GAHT-related physical characteristics, such as breast development in trans women and increased body hair in trans men, are similar between groups, are associated with higher QoL scores, and that sociodemographic parameters may impact these associations. Healthcare providers might consider these factors when planning interventions to improve QoL in transgender individuals.

UNASSIGNED: Most people with gender dysphoria have to face various stressful conditions, which make them more vulnerable to the development of psychopathological symptoms.
UNASSIGNED: The main goal was to compare psychopathological symptoms between individuals with gender dysphoria and those from the general population. Other secondary aims were to determine if there were differences between gender [male to females (MtFs) and female to males (FtMs)] and also according to cross-sex hormone therapy.
UNASSIGNED: Symptom Checklist 90 Revised (SCL-90-R) questionnaire was administered to a sample of 205 subjects with gender dysphoria (MtFs = 129 and FtMs = 76). The control group included 530 individuals from the general population who took part in the Spanish validation of the SCL-90-R questionnaire.
UNASSIGNED: Overall, individuals with gender dysphoria had higher scores on all SCL-90-R dimensions than the general population, except in the dimension of somatization, in which MtF and FtM subjects scored statistically higher than control males but not than control females. The mean scores of all dimensions except Depression (mean score of 1.17) were below 1, that is, between 0 (not at all) and 1 (occasionally). All dimensions did not differ when comparing MtFs and FtMs nor when comparing gender dysphoric subjects with or without cross-sex hormonal therapy.
UNASSIGNED: The results suggested that most subjects with gender dysphoria attending a gender unit reported higher levels of psychopathology than the general population. However, the scores were indicative of the lack of any clinically relevant psychopathological symptoms.

Testosterone esters are hormones commonly used for affirming gender identity in transmen. The present study evaluates the effect of testosterone on renal morphology and function in an animal model submitted to cross-sex hormone therapy used for transmen. Two-month-old Wistar rats were divided into three groups: male control (MC), female control (FC), and female on testosterone therapy (FTT). The FTT group received testosterone cypionate (3.0 mg/kg, i.m.), and the MC and MF groups received vehicle oil every 10 days for 4 months. Renal function and indirect systolic blood pressure (SBP) measurements were evaluated at 6 months of age. Plasma and urine concentrations of urea, creatinine, sodium, potassium, osmolality, and glomerular filtration rate (GFR) were measured. The kidneys were weighed, paraffin-embedded, and histological sections were prepared to evaluate the glomerular area. We verified that the FTT group, in comparison to FC, had increased kidney weight [MC, 3.2 ± 0.05; FC, 1.8 ± 0.04; FTT, 2.2 ± 0.06; g], decreased urine osmolarity [MC, 486.9 ± 18.3; FC, 1012.0 ± 5.4; FTT, 768.2 ± 40.3 mOsm/L/g kw], reduced GFR [MC, 0.77 ± 0.04; FC, 0.78 ± 0.02; FTT, 0.67 ± 0.03; mL/min/g kw], larger glomerular area [MC, 9334 ± 120.8; FC, 7884 ± 112.8; FTT, 9078 ± 133.4 µm2 ], and higher SBP [MC, 126 ± 3.4; FC, 119 ± 1.0; FTT, 131 ± 1.4; mmHg]. Sodium excretion was higher in FC and FTT in comparison to MC [MC, 0.34 ± 0.05; FC, 0.56 ± 0.06; FTT, 0.54 ± 0.04; mEq/24 h/g kw]. Cross-sex hormone therapy with testosterone in female rats induces renal morphofunctional changes and may underlie increased systolic pressure, suggesting an adaptation similar to what is observed in transmen on long-term testosterone therapy.

Individuals with gender incongruence (GI) experience serious distress due to incongruence between their gender identity and birth-assigned sex. Sociological, cultural, interpersonal, and biological factors are likely contributory, and for some individuals medical treatment such as cross-sex hormone therapy and gender-affirming surgery can be helpful. Cross-sex hormone therapy can be effective for reducing body incongruence, but responses vary, and there is no reliable way to predict therapeutic outcomes. We used clinical and MRI data before cross-sex hormone therapy as features to train a machine learning model to predict individuals\' post-therapy body congruence (the degree to which photos of their bodies match their self-identities). Twenty-five trans women and trans men with gender incongruence participated. The model significantly predicted post-therapy body congruence, with the highest predictive features coming from the cingulo-opercular (R2 = 0.41) and fronto-parietal (R2 = 0.30) networks. This study provides evidence that hormone therapy efficacy can be predicted from information collected before therapy, and that patterns of functional brain connectivity may provide insights into body-brain effects of hormones, affecting one\'s sense of body congruence. Results could help identify the need for personalized therapies in individuals predicted to have low body-self congruence after standard therapy.

CME: Hormonal Therapy for Gender Incongruence and Gender Dysphoria Abstract. The discrepancy between the inherited gender and the perceived gender identity is called gender incongruity. In this article the major indications, contraindications and therapeutic steps for gender reassignment surgery and hormonal therapy are discussed and summarized.
Zusammenfassung. Die Nichtübereinstimmung der Geschlechtsidentität mit dem angeborenen Geschlecht wird als «Geschlechts-/Genderinkongruenz» bezeichnet und das Leiden um diese Inkongruenz als «Geschlechts-/Genderdysphorie». In diesem Beitrag werden die wichtigsten Indikationen, Kontraindikationen und therapeutischen Massnahmen praxisrelevant diskutiert.

Sex differences in visuospatial cognition have long been reported, with men being advantaged on the Mental Rotations Test (MRT). The data, however, are variable, and sensitive to design parameters. When men and women are compared directly, with women in different hormonal milieus combined, there seem to be sex differences. When women alone are studied, taking into account different ovarian steroid concentrations and treatments, MRT performance varies with these changes. Indeed, several reports describe better performance among women with reduced estrogens. To better understand whether the sex difference in MRT persists once hormonal status is considered, we recruited reproductive age adults designated male and female at birth (MAB, FAB), and administered the Vandenberg-Kuse (V/K) MRT-comparing performance among MAB (n = 169) and FAB (n = 219). For FAB combined, we found a sex difference with MAB performing better than FAB. However, when FAB were analyzed by current menstrual cycle phase (Early Follicular (EF), Periovulatory (PO), Midluteal (ML)) or by hormone therapy (transmasculine testosterone administration (TM+), oral contraceptive (OC) ingestion prior to (OC+) or after cognitive testing (OC-)), low-estradiol groups (EF, OC-, TM+) performed as strongly as MAB, and had better MRT than cycling FAB in high-estradiol menstrual cycle phases (PO, ML). On a verbal memory control task, neither a sex difference nor a low estrogen advantage was detected, although performance varied with hormonal milieu. Our findings support a dynamic model of spatial performance and suggest that both MAB and FAB perform strongly on MRT, contingent on hormonal status.