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OBJECTIVE: To assess the association between varicocele and hypogonadism, or erectile dysfunction. METHODS: We searched MEDLINE, EMBASE, LILACS, CENTRAL, and other sources. We included cohort, case-control, and cross-sectional studies. The primary outcome was the association between varicocele and hypogonadism, or erectile dysfunction, and the secondary outcome included semen analysis. We assessed the risk of bias with the Newcastle-Ottawa Scale. We performed statistical analysis in Review Manager 5.3 and reported information about the Odds Ratio (OR) with a 95% confidence interval. We produced a forest plot for the primary outcome. RESULTS: We included ten studies in qualitative analysis and six studies in quantitative analysis. Most of the cross-sectional studies showed a low risk of bias, not so for the two case-control studies, which represented a high risk of bias. Most of the reports described a correlation between having varicocele and presenting low testosterone levels: the meta-analysis showed that there is a significant association between varicocele and hypogonadism (OR 3.27 95% CI 1.23 to 8.68). Regarding varicocele and erectile, only one study showed a significant difference in erectile function in comparison to varicocele patients and men without varicocele. CONCLUSION: There is an association between varicocele presence and hypogonadism, although more studies are needed. Besides, not much is reported about an association between varicocele and erectile dysfunction, but impairment can occur through hormone disturbances.

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Resumo Fundamento: A deficiência de testosterona (DT) é uma condição prevalente em nosso meio e ainda muito negligenciada. A hipertensão arterial (HA) é um de seus possíveis fatores associados. Objetivos: Determinar a prevalência de DT em uma população masculina hipertensa e os fatores associados à sua ocorrência, como idade, tempo de diagnóstico de HA, número de classes de anti-hipertensivos, índice de massa corporal (IMC), diabetes, dislipidemia, doença renal crônica (DRC), sintomas positivos de DT (questionário ADAM positivo) e uso de espironolactona. Métodos: Estudo transversal com aplicação do questionário ADAM, e avaliação de dados bioquímicos, clínicos e antropométricos. Os pacientes foram estratificados em grupos de DT e testosterona normal. As variáveis categóricas foram comparadas pelo teste do qui-quadrado e as variáveis contínuas pelo teste de Mann-Witney; as variáveis com significância (p<0,05) foram submetidas à regressão linear multivariada. Resultados: A prevalência de DT foi de 26,8%. Houve associação entre DT e IMC (p=0,0007), mas não houve com idade (p=0,0520), tempo de diagnóstico de HA (p=0,1418), número de classes de anti-hipertensivos (p=0,0732), diabetes (p=0,1112); dislipidemia (p=0,3888); presença de DRC (p=0,3321); uso de espironolactona (p=0,3546) e questionário ADAM positivo (p=0,2483). Conclusões: A prevalência de DT foi alta e houve associação positiva com IMC. A testosterona total (TT) declinou 8,44 ng/dL com o aumento de 1 kg/m2 no IMC e caiu 3,79 ng/dL com o avanço em um ano na idade.

Abstract Background: Testosterone deficiency (TD) is a prevalent condition in our midst and still very neglected. Arterial hypertension (AH) is one of the possible associated factors. Objectives: To determine the prevalence of TD in a hypertensive male population and the factors associated with its occurrence, such as age, time since hypertension diagnosis, number of antihypertensive classes, body mass index (BMI), diabetes, dyslipidemia, chronic kidney disease (CKD), positive symptoms of TD (positive ADAM questionnaire) and use of spironolactone. Methods: Cross-sectional study with administration of the ADAM questionnaire, assessment of biochemical, clinical, and anthropometric data. Patients were stratified into DT and normal testosterone groups. Categorical variables were compared using the chi-squared test and continuous variables using the Mann-Witney test; variables with significance (p<0,05) were analyzed by multivariable linear regression. Results: The prevalence of TD was 26.36%. There was an association between TD and body mass index (BMI) (p=0.0007) but there was no association with age (p=0.0520), time of hypertension diagnosis (p=0.1418), number of classes of antihypertensive drugs (p=0.732), diabetes (p=0.1112); dyslipidemia (p=0.3888); CKD (p=0.3321); use of spironolactone (p=0.3546) or positive ADAM questionnaire (p=0.2483). Conclusions: TD was highly prevalent and positively associated with BMI. Total testosterone (TT) declined by 8.44ng/dL with a one unit increase in BMI and dropped by 3.79ng/dL with a one-year increase in age.

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Abstract Objective: To evaluate hypothalamic-pi- tuitary-gonadal (HPG) axis alterations at 1 and 12 months after kidney transplan- tation (KT) and their association with in- sulin resistance. Methods: A retrospective clinical study was conducted in a tertiary care center in kidney transplantation recipients (KTRs) aged 18- 50 years with primary kidney disease and stable renal graft function. LH, FSH, E2/T, and HOMA-IR were assessed at 1 and 12 months after KT. Results: Twenty-five KTRs were included; 53% were men, and the mean age was 30.6±7.7 years. BMI was 22.3 (20.4-24.6) kg/m2, and 36% had hypogonadism at 1 month vs 8% at 12 months (p=0.001). Re- mission of hypogonadism was observed in all men, while in women, hypogonadotropic hypogonadism persisted in two KTRs at 12 months. A positive correlation between go- nadotrophins and age at 1 and 12 months was evident. Fifty-six percent of patients had insulin resistance (IR) at 1 month and 36% at 12 months (p=0.256). HOMA-IR showed a negative correlation with E2 (r=- 0.60; p=0.050) and T (r=-0.709; p=0.049) at 1 month, with no correlation at 12 months. HOMA-IR at 12 months after KT correlated positively with BMI (r=0.52; p=0.011) and tacrolimus dose (r=0.53; p=0.016). Conclusion: Successful KT restores the HPG axis in the first year. Hypogonadism had a negative correlation with IR in the early pe- riod after KT, but it was not significant at 12 months.

Resumo Objetivo: Avaliar as alterações do eixo hipotálamo-hipófise-gonadal (HHG) em 1 e 12 meses após transplante renal (TR) e sua associação com a resistência à insulina. Métodos: Foi realizado um estudo clínico retrospectivo em um centro de cuidados terciários em receptores de transplante renal (RTR) com idade entre 18-50 anos com doença renal primária e função do enxerto renal estável. LH, FSH, E2/T e HOMA-IR foram avaliados em 1 e 12 meses após o TR. Resultados: foram incluídos 25 RTR; 53% eram homens e a média de idade foi de 30,6±7,7 anos. O IMC foi de 22,3 (20,4-24,6) kg/m2 e 36% apresentaram hipogonadismo em 1 mês vs 8% aos 12 meses (p=0,001). A remissão do hipogonadismo foi observada em todos os homens, enquanto nas mulheres, o hipogonadismo hipogonadotrófico persistiu em dois RTR aos 12 meses. Ficou evidente uma correlação positiva entre gonadotrofinas e idade em 1 e 12 meses. Cinquenta e seis por cento dos pacientes apresentaram resistência à insulina (RI) em 1 mês e 36% aos 12 meses (p=0,256). O HOMA-IR mostrou uma correlação negativa com E2 (r=-0,60; p=0,050) e T (r=-0,709; p=0,049) em 1 mês, sem correlação em 12 meses. O HOMA-IR aos 12 meses após TR correlacionou-se positivamente com o IMC (r=0,52; p=0,011) e a dose de tacrolimus (r=0,53; p=0,016). Conclusão: O TR bem-sucedido restaura o eixo HHG no primeiro ano. O hipogonadismo apresentou uma correlação negativa com a RI no período inicial após o TR, mas essa correlação não foi significativa aos 12 meses.

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INTRODUCTION AND OBJECTIVES: Throughout the coronavirus disease 2019 (COVID-19) pandemic, a greater severity and lethality of the disease has been highlighted in male patients, so we set out to evaluate the prognostic role of serum testosterone levels in the clinical results of this population. METHODS: In this single-center and cross-sectional design, we included male patients admitted to our hospital with COVID-19 confirmed diagnosis. The biochemical analysis included lymphocytes, lactate dehydrogenase (LDH), total testosterone (TT), dehydroepiandrosterone, follicle-stimulating hormone, and luteinizing hormone. Receiver operating characteristic curves, univariate and bivariate analysis, and binary logistic regression for multivariate analysis were performed. A p value<0.05 was consider significant. RESULTS: From 86 men included, 48.8% died. TT levels were lower in non-survivor patients than in survivor patients (4.01nmol/L [0.29-14.93] vs 5.41 (0.55-25.08) nmol/L, p=0.021). The independent risk factors that increased the relative risk (RR) of dying from COVID-19 were: age>59 years (RR 3.5 [95% IC 1.0-11.6], p=0.045), TT levels<4.89nmol/L (RR 4.0 [95% IC 1.2-13.5], p=0.027) and LDH levels>597IU/L (RR 3.9 [95% IC 1.2-13.1], p=0.024). Patients who required mechanical ventilation (p=0.025), had lymphopenia (p=0.013) and LDH levels>597IU/L (p=0.034), had significantly lower TT levels compared to those who did not present these conditions. There were no differences in TT levels between patients who had or did not have comorbidities. CONCLUSIONS: A TT level<4.89nmol/L increase four times the RR of death from COVID-19 in men, regardless of age or presence of comorbidities.

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Los prolactinomas son los tumores funcionantes de hipófisis más frecuentes. Se clasifican según su tamaño en microprolactinomas (menores a 1 cm) y macroprolactinomas (mayor o igual a 1 cm). Estos últimos tienen mayor frecuencia en hombres y en general se diagnostican más tardíamente, cuando aparecen síntomas compresivos. La hiperprolactinemia interfiere con la secreción pulsátil de la hormona liberadora de gonadotropinas (GnRH), lo que genera la inhibición de secreción de hormona luteinizante (LH) y de hormona foliculoestimulante (FSH), y en consecuencia produce hipogonadismo hipogonadotrófico. El presente artículo reporta un caso clínico de un paciente de 26 años, de sexo masculino, en el que se realiza el diagnóstico de hipogonadismo hipogonadotrófico secundario a un macroprolactinoma, en el contexto de una pubertad detenida.

Prolactinomas are the most common functioning pituitary tumors. According to size, they are classified into microprolactinomas (smaller than 1 cm) and macroprolactinomas (larger than or equal to 1 cm). The latter are more frequent among men and in general of late diagnosis upon compressive symptoms. Hyperprolactinemia interferes with the pulsatile secretion of the gonadotrophin releasing hormone (GnRH)) what results in inhibition of the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), what consequently produces hypogonadotrophic hypogonadism. The study reports the clinical case of a 26-year-old male who was diagnosed with hypogonadotrophic hypogonadism secondary to macroprolactinoma, within the context of detained puberty.

Os prolactinomas são os tumores hipofisários funcionantes mais comuns. São classificados de acordo com seu tamanho em microprolactinomas (menos de 1 cm) e macroprolactinomas (maior ou igual a 1 cm). Estas últimas são mais frequentes em homens e geralmente são diagnosticadas mais tarde, quando aparecem sintomas compressivos. A hiperprolactinemia interfere na secreção pulsátil do hormônio liberador de gonadotropina (GnRH), levando à inibição da secreção do hormônio luteinizante (LH) e do hormônio folículo-estimulante (FSH) e, consequentemente, hipogonadismo hipogonadotrófico. Este artigo relata o caso clínico de um paciente do sexo masculino de 26 anos, no qual é feito o diagnóstico de hipogonadismo hipogonadotrófico secundário a um macroprolactinoma, no contexto de puberdade interrompida.

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Resumen Introducción: Los trastornos andrológicos son frecuentes en varones con diabetes tipo 2. El objetivo fue evaluar si los médicos que atienden a personas con diabetes tipo 2 abordan problemas andro lógicos como disfunción sexual eréctil, disminución de libido y síntomas de hipogonadismo. Métodos: Se llevó a cabo una encuesta anónima a 171 médicos, de ellos 113 fueron mujeres (66.1%) con una edad media de 46 ± 10 años (mujeres: 45 ± 10 y varones: 49 ± 10, p = 0.006). Resultados: No hubo diferencias en las res puestas según el género. El 44.4% (n = 76) y el 55.6% (n = 95) no preguntan sobre la presencia de disfunción sexual eréctil y/o disminución de libido, respectivamente. El 50.9% (n = 87) no solicitó medición de testosterona en pacientes con síntomas de hipogonadismo. El 65.8% de los participantes respondió que el reemplazo con testosterona puede mejorar el perfil metabólico de la diabetes mellitus tipo 2 y los síntomas sexuales. El 74.7% de los encuestados afirmó que la medición de testosterona debería realizarse ante la presencia de síntomas compatibles con hipogonadismo. El 63.2% (n = 108) mostró interés en formación sobre temas relacionados a diabetes tipo 2 y trastornos de la esfera sexual. Conclusión: Un gran porcentaje de médicos que asisten a varones con diabetes tipo 2 no indaga sobre trastornos andrológicos. Es necesario concientizar y entrenar a los médicos, para detectar, tratar y/o derivar estos problemas de salud tan frecuentes, no solo para mejorar la calidad de vida de los pacientes sino para responder y prevenir efectivamente a un problema mayor de salud.

Abstract Introduction: Our objective was to assess whether physicians who care for people with type 2 dia betes address andrological symptoms such as erectile sexual dysfunction, decreased libido, and symptoms and/ or signs of hypogonadism. Methods: An anonymous survey was carried out with 171 doctors, 113 were females (66.1%), the mean age was 46 ± 10 years (females: 45 ± 10 and males: 49 ± 10, p = 0.006). Results: There were no differences in responses according to gender. Regarding the presence of erectile sexual dysfunction and/or decreased libido, 44.4% (n = 76) and 55.6% (n = 95) did not ask about them, respectively. In patients with symptoms of hypogonadism, 50.9% (n = 87) did not request a testosterone measurement. Regarding the improvement of the metabolic profile of type 2 diabetes mellitus and sexual symptoms after replacement with testosterone, 65.8% of the respondents answered that both conditions could improve after treatment. In the presence of symptoms compatible with hypogonadism, 74.7% of those surveyed stated that the measurement of testosterone should be performed. A total of 108 (63.2%) showed interest in being trained on topics related to type 2 diabetes and disorders of the sexual sphere. Conclusion: A large percentage of physicians who take care of men with type 2 diabetes do not inquire about andrological disorders. It is necessary to raise awareness and train doctors to detect, treat and/or refer these frequent health problems, not only to improve the quality of life of patients but also to effectively respond and prevent a major health problem.

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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)

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ABSTRACT We report a 27 -year-old male referred because of hypergonadotropic hypogonadism with low testosterone and azoospermia. At 23 years of age, he underwent an excision of a hypoechoic 0.7 cm nodule of the left testicle. The pathological diagnosis was a Leydig cell tumor. In the right testicle, there were three nodules at ultrasound, the biggest measuring 0.6 cm. Four years later, the nodules in the right testicle were still present and the larger nodule was excised. The biopsy showed tubules with only Sertoli cells in the perinodular zone. Diffuse and nodular hyperplasia of the Leydig cells was found in the interstitium. The pathological diagnosis was Sertoli syndrome with severe hyperplasia of the Leydig cells. With testosterone therapy, LH decreased, and the nodules disappeared. Thereafter, upon interrupting therapy, LH increased, and the nodules reappeared in two occasions. Resuming testosterone treatment, the nodules disappeared again, suggesting a Leydig cell hyperplasia dependent on chronic LH stimulation.

Presentamos un varón de 27 años referido por hipogonadismo hipergonadotrófico con testosterona baja y azoospermia. El paciente tenía el antecedente de un nódulo sólido hipoecogénico de 0,7 cm en el testículo izquierdo, extirpado los 23 años de edad en el año 2002 y diagnosticado patológicamente como tumor de células de Leydig. En ese año se encontraron tres nódulos en el testículo derecho por ultrasonografía, el mayor de 0,6 cm. Cuatro años después, en 2007, los micronódulos del testículo derecho seguían presentes. El mayor de ellos fue extirpado. En la biopsia, había túbulos con solo células de Sertoli en la zona perinodular. En el intersticio había hiperplasia difusa y nodular de las células de Leydig. El diagnóstico patológico fue un síndrome de Sertoli con severa hiperplasia de células de Leydig. La terapia con testosterona disminuyó la LH y los nódulos inesperadamente desaparecieron. En dos ocasiones, al interrumpir esta terapia, la LH aumentó y los nódulos reaparecieron. Este proceso revirtió nuevamente con el uso de testosterona, sugiriendo una hiperplasia de células de Leydig dependiente del estímulo crónico de LH.

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RESUMEN Objetivos: describir un caso de falla ovárica secundaria a una variante patogénica homocigota en el gen STAG3 no reportada previamente. Materiales y métodos: paciente de 16 años con amenorrea primaria y ausencia de características sexuales secundarias, en quien se documentó hipotiroidismo autoinmune, pobre desarrollo genital y cintilla gonadal, por lo cual se realizó secuenciación de exorna clínico. Se identificó una variante homocigota patogénica previamente no reportada en el gen STAG3, el cual ha sido relacionado con insuficiencia ovárica prematura (IOP). Conclusiones: en este caso, la realización de exorna clínico fue determinante para identificar una alteración del gen STAG, probablemente asociada a la IOP y el pronóstico a largo plazo de la paciente. Se establece una nueva variante patogénica c.2773delT; p.Ser925Profs*6 del gen STAG3 asociada a la IOP.

ABSTRACT Objectives: To describe a case of ovarian failure secondary to a homozygous pathogenic variant in the STAG3 gene not previously reported. Material and methods: A 16-year-old patient with primary amenorrhea and absence of secondary sexual characteristics, with documented autoimmune hypothyroidism, poor genital and gonadal streak development which prompted the performance of clinical exorne sequencing. A homozygous pathogenic variant not previously reported in the STAG3 gene, which has been associated with premature ovarian insufficiency (POI), was identified. Conclusions: In this case, clinical exorne sequencing was key for identifying a STAG gene abnormality, probably associated with POI and long term prognosis for the patient. A new pathogenic variant c.2773delT; p.Ser925Profs*6 of the STAG3 gene associated with POI was established.

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