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PURPOSE: 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). CONCLUSION: 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.

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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.

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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.

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Una persona transgénero es aquella en la cual el género autopercibido difiere del asignado al nacer, mientras que el término cisgénero es utilizado en aquellos individuos no trans. El tratamiento hormonal cruzado (THC) constituye una opción para lograr caracteres sexuales secundarios deseados. Es conocido que los esteroides sexuales desempeñan un rol fundamental en la adquisición de la densidad mineral ósea (DMO) durante la pubertad. Por lo tanto, el impacto del THC sobre la masa ósea se ha convertido en materia de estudio. En estadios puberales tempranos, los análogos de la hormona liberadora de gonadotrofinas (GnRH) son utilizados con un efecto reversible. Si bien la DMO parece mantenerse estable, cuando se compara con una población de referencia del mismo sexo biológico y edad, el Z-score se encuentra por debajo de lo esperado. En adultos, durante el THC no se informaron disminuciones en la DMO. Está reportado que las mujeres trans antes del inicio del TH presentan características densitométricas diferentes de los hombres cisgénero. Hasta el momento, la carga de datos para los calculadores del riesgo de fractura y el software del equipo DXA se basan en el sexo biológico y no en identidad de género. Recientemente, la International Society for Clinical Densitometry (ISCD) emitió sus recomendaciones para la evaluación de la masa ósea en personas transgénero y en aquellos individuos no conformes con el género. Si bien la ISCD sugiere realizar la evaluación únicamente en aquellos pacientes con factores de riesgo, es de importancia realizar DXA basal, sobre todo en mujeres transgénero, para determinar el riesgo inicial de dicha población. En este artículo se revisa la evidencia disponible sobre el impacto del THC en la salud ósea de personas transgénero. (AU)

Cross sex hormone therapy (CSHT) in transgender women (TW) it is an option to achieve desired secondary sexual characteristics. It is known that sex steroids play a fundamental role in the acquisition of bone mineral density during puberty, in addition to determining a different characteristic bone pattern between both biological sexes. So the impact of affirming HT on bone is it has become in subject of study. In early pubertal stages, GnRH analogs are used with a reversible effect. Although bone mineral density (BMD) seems to remain stable, when compared with a reference population of the same biological sex and age, the Z-score is lower than expected. In adults, during CSHT no decreases in BMD were reported. However, it was reported that TW prior to starting CSHT present different densitometric characteristics than cisgender men. So far, the data load for the fracture risk calculators and DXA software is based on biological sex and not gender identity. Recently the ISCD issued its recommendations for the evaluation of bone mass in transgender subjects and in those non-conforming to gender. Although the ISCD suggests performing the evaluation only in those patients with risk factors, our group recognizes that baseline DXA, especially in TW, constitutes a useful tool to determine the initial risk of this population. Our proposal arises from our own experience and from that compiled in the international literature, where it is observed that even without starting CSHT, transgender women have lower BMD. DXA. This article reviews the available evidence regarding the effect of CSHT on health bone in transgender people. (AU)

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CONTEXT: The impact of long-term cross-sex hormone therapy (CSHT) in transgender men and women is still uncertain. OBJECTIVE: To perform a systematic review and meta-analysis and update the evidence regarding the effects of CSHT on bone mineral density (BMD) in transgender men and women. DATA SOURCES: Medline, Cochrane Central Register of Controlled Trials, and Embase were searched for studies published until August 2018. STUDY SELECTION: Of 10,849 studies, 19 were selected for systematic review. All included patients were aged >16 years and received CSHT with BMD assessment by dual-energy X-ray absorptiometry (DXA). DATA EXTRACTION: Data on BMD, CSHT, and clinical factors affecting bone mass were collected. A National Institutes of Health scale was used to assess the quality of studies. DATA SYNTHESIS: Nineteen studies were meta-analyzed (487 trans men and 812 trans women). In trans men, mean BMD difference compared with natal women was not significant in any site in either cross-sectional or before-after studies. In trans women, mean BMD difference was not significant compared with natal men at the femoral neck, total femur, and lumbar spine in cross-sectional studies; before-after studies reported a slight but significant increase in lumbar spine BMD after 12 and ≥24 months of treatment. CONCLUSIONS: Long-term CSHT had a neutral effect on BMD in transgender men. In transgender women, only lumbar spine BMD seemed to be affected after CSHT. This evidence is of low to moderate quality as a result of the observational design of studies, small sample sizes, and variations in hormone therapy protocols.

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A trans-male (TM) is a biologically female person with male gender identity who wishes to acquire male sexual characteristics and fulfil a male social role. To achieve that purpose, both cross-hormonal therapy (CHT) and surgical phalloplasty can be used. We evaluated the short term (12 months) safety profile of CHT using different forms of testosterone available for prescription in Argentina. In this retrospective study, we analyzed the medical history of 30 trans-male patients fitting the inclusion criteria. The mean age of the population was 27 years. The mean basal serum level of testosterone was 0.43 ng/ml, which increased to 6.36 ng/ml (male hormonal levels). The hematocrit increased from a baseline of 40.0 to 45.2% (p < 0.01) and hemoglobin increased from 13.6 to 15.2 g/dl (p < 0.01). Total cholesterol remained stable with values of 175 and 185 mg/dl (p = 0.81). There were no significant changes in serum triglycerides: 88.3 and 102 mg/dl (p = 0.08). LDL increased in the first 6 to 12 months of CHT from 101.2 to 112.5 mg/dl (p = 0.17). At 12 months HDL levels increased from 50.1 to 52 mg/dl (p < 0.01). Hepatic enzymes remained stable. There is no available data regarding safety of testosterone use in TM in our country. In no case did we need to suspend the medication due to unwanted effects.

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Se denomina trans-varón (TV) a una persona de sexo biológico femenino con identidad de género masculino. Para adquirir caracteres sexuales y expresar un rol social semejante podría utilizarse: terapia hormonal cruzada (THC) y/o genitoplastia masculinizante. Se evaluó el perfil de seguridad a corto plazo (primer año) de la THC con las distintas formas farmacéuticas de testosterona disponibles en nuestro país. El estudio se realizó de manera retrospectiva, analizando las historias clínicas de 30 pacientes trans-varón que cumplían con los requisitos para ser incluidos. La edad media de la población fue de 27 años. La media basal de testosterona fue de 0.43 ng/ml, que luego aumentó a 6.36 ng/ml (valores normales para sexo masculino). El hematocrito incrementó de su valor basal 40.0 a 45.2% (p < 0.01) mientras la Hb de 13.6 a 15.2 g/dl (p < 0.01). El colesterol total se mantuvo estable con valores de 175 y 185 mg/dl (p = 0.81). No hubo cambios significativos en triglicéridos: 88.3 y 102 mg/dl (p = 0.08). El colesterol LDL incrementó en los primeros 6 a 12 meses de THC de 101.2 a 112.5 mg/dl (p = 0.17). A los 12 meses los niveles de colesterol HDL aumentaron de 50.1 a 52.0 mg/ dl (p < 0.01). Las enzimas hepáticas se mantuvieron estables. No existen datos en nuestro país sobre seguridad de la testosterona en TV. No tuvimos necesidad de suspender la medicación por efectos no deseados en los parámetros estudiados.

A trans-male (TM) is a biologically female person with male gender identity who wishes to acquire male sexual characteristics and fulfil a male social role. To achieve that purpose, both cross-hormonal therapy (CHT) and surgical phalloplasty can be used. We evaluated the short term (12 months) safety profile of CHT using different forms of testosterone available for prescription in Argentina. In this retrospective study, we analyzed the medical history of 30 trans-male patients fitting the inclusion criteria. The mean age of the population was 27 years. The mean basal serum level of testosterone was 0.43 ng/ml, which increased to 6.36 ng/ml (male hormonal levels). The hematocrit increased from a baseline of 40.0 to 45.2% (p < 0.01) and hemoglobin increased from 13.6 to 15.2 g/dl (p < 0.01). Total cholesterol remained stable with values of 175 and 185 mg/dl (p = 0.81). There were no significant changes in serum triglycerides: 88.3 and 102 mg/dl (p = 0.08). LDL increased in the first 6 to 12 months of CHT from 101.2 to 112.5 mg/dl (p = 0.17). At 12 months HDL levels increased from 50.1 to 52 mg/dl (p < 0.01). Hepatic enzymes remained stable. There is no available data regarding safety of testosterone use in TM in our country. In no case did we need to suspend the medication due to unwanted effects.

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Testosterone is the main hormonal agent used for cross-sex hormone therapy in female-to-male transgender persons. Our aim was to systematically review the literature concerning the effects of testosterone on body mass index (BMI), blood pressure, hematocrit, hemoglobin, lipid profile, and liver enzymes in transgender men. PUBMED and EMBASE were searched for studies published until March 2017. Studies were included if they reported interventions with any dose of testosterone and comparison of variables before and during treatment. Of 455 potentially eligible articles, 13 were reviewed. Study duration ranged from 6 to 60 months, sample size ranged from 12 to 97 patients, and the most common treatment was parenteral testosterone undecanoate 1000 mg/12 weeks. Slight but significant increases in BMI were reported (from 1.3 to 11.4%). Three out of seven studies assessing the impact of different testosterone formulations on blood pressure detected modest increases or clinically irrelevant changes in this variable. In another study, however, two patients developed hypertension, which was resolved after cessation of testosterone therapy. Decreases in HDL-cholesterol and increases in LDL-cholesterol were consistently observed. Eight studies observed a relationship between testosterone and increased hemoglobin (range: 4.9-12.5%) and hematocrit (range: 4.4-17.6%), but discontinuation of androgen therapy was not necessary. In one study, two patients developed erythrocytosis (hematocrit >52%) after 9 and 12 months of treatment. One study analyzing testosterone formulations observed smaller increases in hemoglobin and hematocrit with testosterone gel. Six studies assessing liver function showed slight or no changes. Overall, the quality of evidence was low, given the lack of randomized clinical/controlled trials and the small sample sizes. In conclusion, exogenous testosterone administration to transgender men was associated with modest increases in BMI, hemoglobin/hematocrit, and LDL-cholesterol, and with decreases in HDL-cholesterol. Long-term studies are needed to assess the long-term risks of testosterone therapy, particularly as they relate to cardiometabolic risks such as diabetes, dyslipidemia and the metabolic syndrome.

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