Sex hormones and vascular reactivity: a temporal evaluation in resistance arteries of male rats.

The role of androgens in vascular reactivity is controversial, particularly regarding their age-related actions. The objective of this study was to conduct a temporal evaluation of the vascular reactivity of resistance arteries of young male rats, as well as to understand how male sex hormones can influence the vascular function of these animals. Endothelium-mediated relaxation was characterized in third-order mesenteric arteries of 10-, 12-, 16-, and 18w (week-old) male rats. Concentration-response curves to acetylcholine (ACh, 0.1 nmol/L-10 µmol/L) were constructed in arteries previously contracted with phenylephrine (PE, 3 µmol/L), before and after the use of nitric oxide synthase or cyclooxygenase inhibitors. PE concentration-response curves (1 nmol/L-100 µmol/L) were also built. The levels of vascular nitric oxide, superoxide anion, and hydrogen peroxide were assessed and histomorphometry analysis was performed. The 18w group had impaired endothelium-dependent relaxation. All groups showed prostanoid-independent and nitric oxide-dependent vasodilatory response, although this dependence seems to be smaller in the 18w group. The 18w group had the lowest nitric oxide and hydrogen peroxide production, in addition to the highest superoxide anion levels. Besides functional impairment, 18w animals showed morphological differences in third-order mesenteric arteries compared with the other groups. Our data show that time-dependent exposure to male sex hormones appears to play an important role in the development of vascular changes that can lead to impaired vascular reactivity in mesenteric arteries, which could be related to the onset of age-related cardiovascular changes in males.

Effects of aging and the body mass index on male sex hormones: a cross-sectional study in 701 Brazilian men / Efeitos do envelhecimento e do índice de massa corporal sobre os hormônios sexuais masculinos: um estudo transversal em 701 homens brasileiros

Background: Some studies indicated that body mass index (BMI) is inversely proportional to serum testosterone concentrations in men. Purposes: This study aimed to analyze the effects of aging and obesity on total testosterone (TT), free testosterone (FT), bioavailable testosterone (BT), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) levels. Methods: A cross-sectional study was performed to assess the clinical and laboratory profiles of 701 patients treated at a private urology clinic in Ponta Grossa, Brazil, from January 2016 to December 2018. Results: Patients' age ranged from 16 to 88 years (mean, 56.9 ± 13.62 years). Age did not significantly influence serum TT concentrations, except compared to patients aged >70 years. However, changes were observed in FT and BT (p < 0.05). The mean SHBG increased with age (p < 0.05). A tendency toward LH elevation was observed in older patients, but it was not statistically significant. An inverse proportional relationship between TT, FT, and BT and the testosterone deficiency rate (TT < 300 ng/dL) was observed within BMI groups (p < 0.05). The testosterone deficiency rate was 21.5% in individuals with normal BMI, 29% in overweight individuals, and 37% in obese individuals. Conclusions: Aging affected the testosterone concentrations in men and became increasingly evident using FT and BT instead of TT. SHBG increased with age. Obesity was associated with a decrease in TT, FT, and BT but also increased the rate of hypogonadism. (AU)

Fundamentos: Alguns estudos indicam que o índice de massa corporal (IMC) é inversamente proporcional à con-centração de testosterona sérica em homens. Objetivos: O objetivo deste estudo é analisar o efeito do envelhe-cimento e da obesidade na testosterona biodisponível total e livre, bem como nos níveis de hormônio luteinizante e globulina ligadora de hormônio sexual. Métodos: Foi realizado um estudo transversal abordando o perfil clínico e laboratorial de 701 pacientes atendidos em uma clínica privada de urologia em Ponta Grossa, Brasil, de janei-ro de 2016 a dezembro de 2018. Resultados: A idade dos pacientes variou de 16 a 88 anos (média de 56,9 ± 13,62 anos). A idade não influenciou significativamente as concentrações séricas de testosterona total, exceto quando comparada a pacientes com mais de 70 anos. No entanto, foi observada diferença na testosterona livre e biodisponível (p <0,05). A média de globulina de ligação aos hormônios sexuais aumentou com a idade (p <0,05). Embora uma tendência à elevação da luteinização tenha sido observada em pacientes mais idosos, ela não foi significativa. Relação inversa entre testosterona total, livre e biodisponível e taxa de deficiência de testosterona (testosterona total <300 ng / dL) foi observada dentro dos grupos de índice de massa corporal (p <0,05). A taxa de deficiência de testosterona em indivíduos com índice de massa corporal normal foi de 21,5%, indivíduos com sobre-peso foi de 29% e em indivíduos com obesidade foi de 37%. Conclusões: O envelhecimento afetou a concentração de testosterona em homens, mais evidente ao avaliar testosterona livre e biodisponível em vez de testosterona total. A globulina de ligação aos hormônios sexuais aumentou com a idade. A obesidade foi associada à redução da testosterona total, livre e biodisponível e ao aumento da taxa de hipogonadismo. (AU)

Body, metabolic and renal changes following cross-sex estrogen/progestogen therapy in a rodent model simulating its use by transwomen.

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.

Physical and Sociodemographic Features Associated With Quality of Life Among Transgender Women and Men Using Gender-Affirming Hormone Therapy.

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.

Cross-sex testosterone therapy modifies the renal morphology and function in female rats and might underlie increased systolic pressure.

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.

Increased oxidative stress and cancer biomarkers in the ventral prostate of older rats submitted to maternal malnutrition.

The concept of Developmental Origins of Health and Disease (DOHaD) states that exposure to malnutrition early in life increase the incidence of non-communicable chronic diseases throughout the lifespan. In this study, a reduction in serum testosterone and an increase in estrogen levels were shown in older rats born to protein malnourished dams (6% protein in the diet) during gestation and lactation. Intraprostatic levels of reduced glutathione were decreased, while tissue expression of glutathione S-transferase pi and sulfiredoxin-1 were increased in these animals. Strong immunostaining for alfametilacil CoA racemase (AMACR), vascular endothelial growth factor-A (VEGF-A), and aquaporin-1 (AQP1) was also observed. In silico analysis confirmed commonly deregulated proteins in the ventral prostate of old rats and patients with prostate cancer. In conclusion, the increase in oxidative stress associated with an imbalance of sex hormones may contribute to prostate carcinogenesis in offspring, highlighting early-life malnutrition as a key risk factor for this malignance.

Toll-Like Receptors Represent an Important Link for Sex Differences in Cardiovascular Aging and Diseases.

Human life span expectancy has increased, and aging affects the organism in several ways, leading, for example, to an increased risk of cardiovascular diseases. Age-adjusted prevalence of the cardiovascular diseases is higher in males than females. Aging also affects the gonadal sex hormones and the sex differences observed in cardiovascular diseases may be therefore impacted. Hormonal changes associated with aging may also affect the immune system and the immune response is sexually different. The immune system plays a role in the pathogenesis of cardiovascular diseases. In this context, toll-like receptors (TLRs) are a family of pattern recognition receptors of the immune system whose activation induces the synthesis of pro-inflammatory molecules. They are expressed throughout the cardiovascular system and their activation has been widely described in cardiovascular diseases. Some recent evidence demonstrates that there are sex differences associated with TLR responses and that these receptors may be affected by sex hormones and their receptors, suggesting that TLRs may contribute to the sex differences observed in cardiovascular diseases. Recent evidence also shows that sex differences of TLRs in cardiovascular system persists with aging, which may represent a new paradigm about the mechanisms that contribute to the sex differences in cardiovascular aging. Therefore, in this mini review we describe the latest findings regarding the sex differences of TLRs and associated signaling in cardiovascular diseases during aging.

Salud ósea en personas transgénero / Bone health in transgender subjects

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)

Densidad mineral ósea y composición corporal en mujeres transgénero previamente al tratamiento hormonal cruzado: ¿hay diferencias con hombres cisgénero? / Bone mineral density and body composition in transgender females prior to cross-sex hormone treatment: is there any difference with cisgender males?

Se denomina transgénero mujer (TM) a un varón biológico con identidad de género femenina. El tratamiento hormonal cruzado (THC) es una de las opciones para lograr caracteres sexuales del género autopercibido. Realizamos un estudio de diseño transversal, observacional y analítico para evaluar la densidad mineral ósea, composición corporal y fuerza muscular antes de iniciar la hormonización. Un total de 26 TM en condiciones de ingresar en el estudio fueron comparadas con hombres cisgénero de similar edad (mediana 23,5 vs. 25,5 años). Basalmente, las TM presentaron menor densidad ósea en columna lumbar (1,040 vs. 1,280 g/cm2; p=0,01), cadera total (0,970 vs. 1,070 g/cm2; p=0,01) y cuerpo entero (1,080 vs. 1,220 g/cm2; p<0,01). Observamos, además, menor masa muscular en brazos (5,033 vs. 6,212 kg; p<0,01) y piernas (16,343 vs. 18,404 kg; p=0,02), acompañada de menor fuerza muscular de puño (p<0,01). Concluimos que las TM presentaron características diferentes de la biología masculina aun sin haber iniciado el THC. Sugerimos incluir la evaluación de la densidad mineral ósea en la evaluación inicial de esta población, dados los hallazgos identificados. (AU)

A trans-woman (TW) is a biologically male person with female gender identity. Cisgender denotes a person whose sense of personal identity and gender corresponds with its birth sex. Cross-sex hormone therapy (CSHT) is one of the options to achieve secondary characteristics of the self-perceived gender. We performed a cross-sectional study. Bone mineral density (BMD), body composition, and muscle strength before starting CSHT were assessed. Twenty-six TW (median age 23.5 years) and cisgender males (median age 25.5 years) were matched for age. TW had less BMD at the lumbar spine (1.040 vs 1.280 g/cm2; p=0.01), total hip (0.970 vs 1.070 g/cm2; p=0.01), and total body (1.080 vs 1.220 g/cm2; p<0.01). They also had less skeletal muscle mass in the arms (5.033 vs 6.212 kg; p<0.01) and legs (16.343 vs 18.404 kg; p=0.02), associated with lower grip strength (p<0.01). It appears that bone and muscle characteristics of TW before starting CSHT differ from cisgender men. Taking these findings into account, we suggest the inclusion of BMD in the initial evaluation of TW. (AU)

Bone Mass Effects of Cross-Sex Hormone Therapy in Transgender People: Updated Systematic Review and Meta-Analysis.

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.

Sex hormone binding globulin during an annual reproductive cycle in the hepatopancreas and ovary of pejerrey (Odontesthes bonariensis).

In the present study, we determined the hepatopancratic shbg transcript abundance and ovarian immunoreactive Shbg (ir-Shbg) localization in pejerrey females at different gonadal stages during an annual ovarian cycle. In the hepatopancreas, shbg expression remains was constant in pre-vitellogenic stages, decreased at final vitellogenesis to increase again in final maturation and atretic stages to previous levels at post-vitellogenic stages. Related to this, also we found a negative significant relation between sex steroid and shbg expression. On the other hand, in the ovary we found ir-Shbg inside of cortical alveoli, from previtellogenic stages to final maturation. This localization of Shbg in a teleost fish ovary suggests a new role for Shbg in oocytes, that may also extend the oocyte fertilization/development process.

[Short-term safety profile of cross-hormonal therapy in trans-male subjects]. / Perfil de seguridad a corto plazo de la terapia hormonal cruzada en trans-varones.

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.

Perfil de seguridad a corto plazo de la terapia hormonal cruzada en trans-varones / Short-term safety profile of cross-hormonal therapy in trans-male subjects

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.

New-onset lupus nephritis after male-to-female sex reassignment surgery.

We report an original case of a 27-year-old transgender woman who developed lupus nephritis after male-to-female sex reassignment surgery. The patient had been taking hormones to induce feminization since the age of 18. She was admitted with malar "butterfly" rash, anasarca and hypertension, associated with an increase in serum creatinine (1.7 mg/dl). Renal involvement was characterized by nephritic and nephrotic syndrome. Autoantibody tests were positive for antinuclear antibodies and anti-double-stranded DNA, and complement levels were markedly reduced. Renal biopsy demonstrated diffuse proliferative glomerulonephritis and granular immune complexes deposits with a "full-house" pattern at the immunofluorescence level. The induction treatment was realized with corticosteroid and cyclophosphamide and maintenance immunosuppression phase with mycophenolate, obtaining complete remission. We speculated that lupus nephritis was induced by estrogens and antiandrogen therapy and gonadectomy. In the present case, we discuss the role of sex hormones in systemic lupus erythematosus onset and review the cases linked to transgender patients.

Aqueous solution interactions with sex hormone-binding globulin and estradiol: a theoretical investigation.

Sex hormone-binding globulin (SHBG) is a binding protein that regulates the availability of steroid hormones in the plasma. Although best known as a steroid carrier, recent studies have associated SHBG in modulating behavioral aspects related to sexual receptivity. Among steroids, estradiol (17ß-estradiol, oestradiol or E2), documented as the most active endogenous female hormone, exerts important physiological roles in both reproductive and non-reproductive functions. In this framework, we employed molecular dynamics (MD) and docking techniques for quantifying the interaction energy between a complex aqueous solution, composed by different salts, SHBG and E2. As glucose concentration resembles measured levels in diabetes, special emphasis was devoted to analyzing the interaction energy between this carbohydrate, SHBG and E2 molecules. The calculations revealed remarkable interaction energy between glucose and SHBG surface. Surprisingly, a movement of solute components toward SHBG was observed, yielding clusters surrounding the protein. The high energy and short distance between glucose and SHBG suggests a possible scenario in favor of a detainment state between the sugar and the protein. In this context, we found that glucose clustering does not insert modification on binding site area nor over binding energy SHBG-E2 complex, in spite of protein superficial area increment. The calculations also point to a more pronounced interaction between E2 and glucose, considering the hormone immersed in the solution. In summary, our findings contribute to a better comprehension of both SHBG and E2 interplay with aqueous solution components.

Impact of cross-sex hormone therapy on bone mineral density and body composition in transwomen.

OBJECTIVE: Cross-sex hormone therapy (CSHT) has been associated with changes in bone and lean/fat mass. This study assessed bone mineral density (BMD), appendicular lean mass (ALM), and total fat mass in transwomen undergoing CSHT. PATIENTS AND DESIGN: We evaluated 142 transwomen (mean age: 33.7 ± 10.3 years; BMI: 25.4 ± 4.6; 86.6% with previous CSHT) during the first 3 months of regular oestrogen treatment (with or without anti-androgens). A reference group including 22 men and 17 cis women was also studied. MEASUREMENTS: Clinical and hormonal evaluation and dual-energy X-ray absorptiometry (DXA). RESULTS: Bone mineral density was similar in trans and reference women, and lower at all sites in transwomen vs men. Low bone mass for age was observed in 18% of transwomen at baseline vs none of the reference women or men. Appendicular lean mass and total fat mass were positively correlated with L1-L4 BMD, explaining 14.9% of the observed variation in lumbar spine BMD and 20.6% of the variation in total femur BMD. Appendicular lean mass was similar in trans and reference women, and lower in transwomen vs men. Total fat mass was lower in trans vs reference women. Densitometry was repeated after a mean of 31.3 ± 6.5 months in 46 transwomen. There was a significant increase in total fat mass and a significant decrease in ALM. Bone mineral density remained stable over time. CONCLUSIONS: The fairly high prevalence of low bone mass in this sample of transwomen from southern Brazil seems to be related to lower ALM. Non-pharmacological lifestyle-related strategies for preventing bone loss could be beneficial for transgender women receiving long-term CSHT.

Low estrogen doses normalize testosterone and estradiol levels to the female range in transgender women

OBJECTIVE: The ideal dosage of cross-sex hormones remains unknown. The aim of this study was to evaluate the luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol and prolactin levels after low-dose estrogen therapy with or without cyproterone acetate in transgender women. METHODS: The serum hormone and biochemical profiles of 51 transgender women were evaluated before gonadectomy. Hormone therapy consisted of conjugated equine estrogen alone or combined with cyproterone acetate. The daily dose of conjugated equine estrogen was 0.625 mg in 41 subjects and 1.25 mg in 10 subjects, and the daily dose of cyproterone acetate was 50 mg in 42 subjects and 100 mg in one subject. RESULTS: Estrogen-only therapy reduced the testosterone, luteinizing hormone and follicle-stimulating hormone levels from 731.5 to 18 ng/dL, 6.3 to 1.1 U/L and 9.6 to 1.5 U/L, respectively. Estrogen plus cyproterone acetate reduced the testosterone, luteinizing hormone and follicle-stimulating hormone levels from 750 to 21 ng/dL, 6.8 to 0.6 U/L and 10 to 1.0 U/L, respectively. The serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol and prolactin in the patients treated with estrogen alone and estrogen plus cyproterone acetate were not significantly different. The group receiving estrogen plus cyproterone acetate had significantly higher levels of gamma-glutamyltransferase than the group receiving estrogen alone. No significant differences in the other biochemical parameters were evident between the patients receiving estrogen alone and estrogen plus cyproterone acetate. CONCLUSION: In our sample of transgender women, lower estrogen doses than those usually prescribed for these subjects were able to adjust the testosterone and estradiol levels to the physiological female range, thus avoiding high estrogen doses and their multiple associated side effects.

Nocturnal Hypoxemia is Associated With Low Testosterone Levels in Overweight Males and Older Men With Normal Weight.

STUDY OBJECTIVES: The relationship among obstructive sleep apnea (OSA), body mass index (BMI), and testosterone levels has long been suggested. Obese men have shown a negative correlation between testosterone level and sleep apnea severity. Yet, little is known about the association between testosterone levels and sleep apnea in men who are not obese. This study evaluated the association between the total testosterone (TT) level and OSA in patients who are not obese. METHODS: A retrospective review of 523 records of patients in whom OSA was diagnosed from 2013-2016 was performed. The study included men with a BMI < 30 kg/m2 and with TT levels measured in a blood sample collected the morning after a sleep study. RESULTS: In all, 153 nonobese men met inclusion criteria, of whom 47 (30.7%) had testosterone levels below the reference values; 44 of these individuals (93.6%) were overweight (P = .029). Reduced testosterone levels showed significant correlations with the oxygen desaturation index, the lowest oxygen saturation < 80% (O2 nadir < 80%), and rapid eye movement (REM) sleep duration, after adjusting for BMI. Among patients with normal weight, only 3 who had O2 nadir < 80% and were older than 50 years presented with a reduced TT level. CONCLUSIONS: In a large population of nonobese men with OSA, we demonstrated that hypoxemia (O2 nadir < 80%) and overweight are associated with reduced testosterone levels. This association was only observed among normal-weight individuals older than 50 years.

Effects of testosterone therapy on BMI, blood pressure, and laboratory profile of transgender men: a systematic review.

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.

Testosterone, Sex Hormone-Binding Globulin and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

ABSTRACT Introduction and aim. Endogenous sex hormones are associated with the risk of diabetes and metabolic syndrome. Recent studies suggested the role of these hormones in nonalcoholic fatty liver disease (NAFLD). We conducted a systematic review and meta-analysis of observational studies investigating the association between sex hormones and NAFLD. Material and methods. A comprehensive search of the databases of the MEDLINE and EMBASE was performed from inception through April 2016. The inclusion criterion was the observational studies that assessed the association of serum total testosterone (TT) and sex-hormone binding globulin (SHBG) and NAFLD. We calculated pooled effect estimates of TT and SHBG with 95% confidence intervals (Cl) comparing between subjects with and without NAFLD by using random-effects model. Results. Sixteen trials comprising 13,721 men and 5,840 women met the inclusion criteria. TT levels were lower in men with NAFLD (MD = -2.78 nmol/l, 95%CI -3.40 to -2.15, I2 = 99%) than in those without. Men with higher TT levels had lower odds of NAFLD whereas higher TT levels increased the odds of NAFLD in women. In both sexes, SHBG levels were lower in patients with NAFLD than controls and this inverse association was stronger in women than men and higher SHBG levels were associated with reduced odds of NAFLD. Conclusion. Our meta-analysis demonstrated a sex-dependent association between TT and NAFLD. Lower TT levels are associated with men with NAFLD and inversely associated with women with NAFLD, whereas higher SHBG levels are associated with lower NAFLD odds in both men and women.