Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer / Baixa testosterona sérica é prognóstica de doença de alto grau em pacientes com câncer de próstata

Summary Objective: To evaluate the relation between serum total testosterone (TT) and prostate cancer (PCa) grade and the effect of race and demographic characteristics on such association. Method: We analyzed 695 patients undergoing radical prostatectomy (RP), of whom 423 had serum TT collected. Patients were classified as having hypogonadism or eugonadism based on two thresholds of testosterone: threshold 1 (300 ng/dL) and threshold 2 (250 ng/dL). We evaluated the relation between TT levels and a Gleason score (GS) ≥ 7 in RP specimens. Outcomes were evaluated using univariate and multivariate analyses, accounting for race and other demographic predictors. Results: Out of 423 patients, 37.8% had hypogonadism based on the threshold 1 and 23.9% based on the threshold 2. Patients with hypogonadism, in both thresholds, had a higher chance of GS ≥ 7 (OR 1.79, p=0.02 and OR 2.08, p=0.012, respectively). In the multivariate analysis, adjusted for age, TT, body mass index (BMI) and race, low TT (p=0.023) and age (p=0.002) were found to be independent risk factors for GS ≥ 7. Among Black individuals, low serum TT was a stronger predictor of high-grade disease compared to White men (p=0.02). Conclusion: Hypogonadism is independently associated to higher GS in localized PCa. The effect of this association is significantly more pronounced among Black men and could partly explain aggressive characteristics of PCa found in this race.

Resumo Objetivo: Avaliar a relação entre testosterona sérica total (TT) e grau do câncer de próstata (CP) e o efeito da raça e de características demográficas sobre essa associação. Método: Foram analisados 695 pacientes submetidos a prostatectomia radical (PR), dos quais 423 tinham medidas dos níveis séricos de TT. Os pacientes foram classificados como portadores de hipogonadismo ou eugonadismo com base em dois limites de testosterona: limite 1 (300 ng/dL) e limite 2 (250 ng/dL). Avaliou-se a relação entre nível de TT e escore Gleason (GS) ≥ 7 em amostras de PR. Os resultados foram avaliados por análises univariada e multivariada, com ajuste para raça e outros fatores prognósticos demográficos. Resultados: Do total de 423 pacientes, 37,8% apresentavam hipogonadismo com base no limite 1, e 23,9% com base no limite 2. Os pacientes com hipogonadismo, independentemente do limite de referência, tiveram uma chance maior de GS ≥ 7 (OR 1,79, p=0,02 e OR 2,08, p=0,012, respectivamente). Na análise multivariada, após ajuste para idade, TT, índice de massa corporal (IMC) e raça, baixo TT (p=0,023) e idade (p=0,002) foram considerados fatores de risco independentes para GS ≥ 7. Entre os indivíduos negros, baixo TT sérico foi mais preditivo de doença de alto grau em comparação com os brancos (p=0,02). Conclusão: O hipogonadismo é independentemente associado a escores mais altos de GS no CP localizado. O efeito dessa associação é significativamente mais pronunciado entre homens negros, o que poderia explicar, em parte, as características agressivas do CP observadas nessa população.

Testosterone Deficiency Increases Hospital Readmission and Mortality Rates in Male Patients with Heart Failure / Deficiência de Testosterona Aumenta Readmissão Hospitalar e Mortalidade em Pacientes do Sexo Masculino com Insuficiência Cardíaca

Background:Testosterone deficiency in patients with heart failure (HF) is associated with decreased exercise capacity and mortality; however, its impact on hospital readmission rate is uncertain. Furthermore, the relationship between testosterone deficiency and sympathetic activation is unknown.Objective:We investigated the role of testosterone level on hospital readmission and mortality rates as well as sympathetic nerve activity in patients with HF.Methods:Total testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized male patients with a left ventricular ejection fraction < 45% and New York Heart Association classification IV. The patients were placed into low testosterone (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography in a subpopulation of 27 patients.Results:Length of hospital stay was longer in the LT group compared to in the NT group (37 ± 4 vs. 25 ± 4 days; p = 0.008). Similarly, the cumulative hazard of readmission within 1 year was greater in the LT group compared to in the NT group (44% vs. 22%, p = 0.001). In the single-predictor analysis, TT (hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.58–4.85; p = 0.02) predicted hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67–8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23–8.69; p = 0.02) predicted increased mortality. Neurohumoral activation, as estimated by MSNA, was significantly higher in the LT group compared to in the NT group (65 ± 3 vs. 51 ± 4 bursts/100 heart beats; p < 0.001).Conclusion:These results support the concept that LT is an independent risk factor for hospital readmission within 90 days and increased mortality in patients with HF. Furthermore, increased MSNA was observed in patients with LT.

Fundamento:A deficiência de testosterona na insuficiência cardíaca (IC) está associada à diminuição da capacidade de exercício e mortalidade, mas o seu impacto sobre as readmissões é incerto. Além disso, sua relação com a ativação simpática é desconhecida.Objetivo:O presente estudo investigou o papel dos níveis de testosterona nas reinternações hospitalares, na mortalidade e na atividade nervosa simpática em pacientes com IC.Métodos:A testosterona total (TT) e a testosterona livre (TL) foram medidas em 110 pacientes do sexo masculino hospitalizados, com fração de ejeção < 45% eclassificação funcional da New York Heart Association (NYHA) IV, qualificados em dois grupos: 66 com baixos níveis de testosterona (BT) e 44 com testosterona normal (TN). Hipogonadismo foi definido como TT < 300 ng/dL e TL < 131 pmol/L. A atividade nervosa simpática muscular (ANSM) foi gravada por microneurografia em uma subpopulação de 27 pacientes.Resultados:O tempo de permanência hospitalar foi maior em pacientes BT em comparação com pacientes TN (37 ± 4 vs. 25 ± 4 dias; p = 0,008). Da mesma forma, o risco cumulativo de readmissão no período de um ano foi maior em pacientes BT (44% vs. 22%, p = 0,001). Na análise de uma única variável preditora, a testosterona total (HR = 2,77, IC 95% 1,58-4,85, p = 0,02) previu readmissão hospitalar no prazo de 90 dias. Na análise de uma única variável preditora, testosterona total (HR = 4,65, IC 95% 2,67-8,10, p = 0,009) e readmissão dentro de 90 dias (HR = 3,27, IC 95% 1,23-8,69, p = 0,02) previram aumento de mortalidade. Ativação neuro-humoral, estimada pela ANSM, foi significativamente maior nos pacientes BT em comparação aos do grupo TN (65 ± 3 vs. 51 ± 4 disparos/100BC; p < 0,001).Conclusão:Estes resultados sustentam o conceito de que BT é um fator de risco independente para a readmissão hospitalar dentro de 90 dias e para aumento de mortalidade em pacientes com IC. Além disso, observou-se aumento da ANSM em pacientes com baixos níveis de testosterona.

A short-term arm-crank exercise program improved testosterone deficiency in adults with chronic spinal cord injury

Purpose To determine the influence of arm-crank exercise in reproductive hormone levels in adults with chronic SCI. Further objectives were to assess the influence of arm-crank exercise on muscle strength and body composition. Materials and Methods Seventeen male adults with complete SCI at or below the 5th thoracic level (T5) volunteered for this study. Participants were randomly allocated to the intervention (n = 9) or control group (n = 8) using a concealed method. The participants in the intervention group performed a 12-week arm-crank exercise program, 3 sessions/week, consisting of warming-up (10-15 min) followed by a main part in arm-crank (20-30 min [increasing 2 min and 30 seconds each three weeks]) at a moderate work intensity of 50-65% of heart rate reserve (HRR) (starting at 50% and increasing 5% each three weeks) and by a cooling-down period (5-10 min). Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone and estradiol were determined by ELISA. Muscle strength (handgrip) and body composition (waist circumference [WC]) were assessed. Results After the completion of the training program, testosterone level was significantly increased (p = 0.0166;d = 1.14). Furthermore, maximal handgrip and WC were significantly improved. Lastly, a significant inverse correlation was found between WC and testosterone (r =- 0.35; p = 0.0377). Conclusion The arm-crank exercise improved reproductive hormone profile by increasing testosterone levels in adults with chronic SCI. A secondary finding was that it also significantly improved muscle strength and body composition in this group. .

FSH-secreting pituitary macroadenoma causing a testosterone deficiency syndrome

FSH-secreting pituitary adenomas can affect sexual and reproductive function. In this article, we have reported the case of a 32-year-old male with secondary infertility. The patient had sexual and reproductive disturbances. The test results of the blood samples indicated obviously decreased testosterone [T] and estradiol [E2] levels. Based on previous hormonal results, the patient received pituitary stimulation and human chorionic gonadotropin [hCG] tests. Both follicle stimulating hormone [FSH] and luteinizing hormone [LH] showed low response during the pituitary stimulation test. The results of the hCG test indicated that T/E2 could recover to a normal level. In addition, this patient was diagnosed with pituitary macroadenoma, which was supported by the pituitary MRI. The man's sexual and reproductive functions recovered following surgery. The pathological results confirmed that the tumor tissue was an FSH-secreting pituitary adenoma by immunohistochemical staining. The purpose of this report was to review the relative literature and discuss the influence of FSH-secreting pituitary adenomas on hormones through the hypothalamus-pituitary-testis axis

Study of testosterone as a predictor of tumor aggressiveness in patients with prostate cancer

Purpose A growing body of evidence suggests that low testosterone can be an independent predictor of adverse clinicopathological features and worse prognosis in prostate cancer (PCa) patients. However, this association is still incompletely understood and the results are divisive. The aim of this study was to analyze testosterone as a predictor of aggressive disease in subjects with clinically localized PCa. Materials and Methods A cohort was conducted including the patients submitted to radical prostatectomy in our institution during a period of four years. The patients had clinically localized disease and their total testosterone (TT) was routinely measured preoperatively in the morning before surgery. They were stratified in groups with low (< 300 ng/dL) and normal TT (≥ 300 ng/dL). Tumor aggressiveness was inferred based on preoperative PSA levels, pathological Gleason score (lower, equal or greater than 7), TNM stage and surgical margins status. Results After analyzing 164 patients we found a significant association between mean preoperative TT and extraprostatic disease (379 for pT3 vs. 421 ng/for pT2 - p < 0.001, AUC > 0.99). Conversely, men with high Gleason score had similar mean TT compared to those with lower scores. Preoperative low TT (defined as TT < 300 ng/dL) could not be statistically correlated with either preoperative PSA levels, pathological Gleason score, extraprostatic extension, positive surgical margins or seminal vesicles involvement. Conclusions This study indicates that testosterone may be a useful predictive tool once pathological extraprostatic extension was somewhat signaled by lower TT levels preoperatively. However, it does not consolidate a clear association between aggressive tumor biology and hypogonadism. .

Medical management of non-obstructive azoospermia

Non-obstructive azoospermia is diagnosed in approximately 10% of infertile men. It represents a failure of spermatogenesis within the testis and, from a management standpoint, is due to either a lack of appropriate stimulation by gonadotropins or an intrinsic testicular impairment. The former category of patients has hypogonadotropic hypogonadism and benefits from specific hormonal therapy. These men show a remarkable recovery of spermatogenic function with exogenously administered gonadotropins or gonadotropin-releasing hormone. This category of patients also includes some individuals whose spermatogenic potential has been suppressed by excess androgens or steroids, and they also benefit from medical management. The other, larger category of non-obstructive azoospermia consists of men with an intrinsic testicular impairment where empirical medical therapy yields little benefit. The primary role of medical management in these men is to improve the quantity and quality of sperm retrieved from their testis for in vitro fertilization. Gonadotropins and aromatase inhibitors show promise in achieving this end point.

Twenty-five milligrams of clomiphene citrate presents positive effect on treatment of male testosterone deficiency - a prospective study

INTRODUCTION: Male testosterone deficiency is associated with bad sexual function and quality of life (QoL). The aim of this study was to determine whether a daily dose of 25 mg clomiphene citrate (CC) is effective in stimulating the endogenous testosterone production pathway and to address the applicability of this medication as a therapeutic option for symptomatic hypogonadism. MATERIALS AND METHODS: This was a prospective study. Men with low sexual desire and testosterone levels (T) below 400 ng/dL were selected to receive CC. Blood samples were obtained to determine baseline measurements of serum T, estradiol, LH, lipid profile and fasting plasma glucose. Each patient was treated with a daily dose of 25 mg CC for at least 3 months. Patients were asked if they experienced any side effects related to the use of CC and if they experienced any improvement in their sexual profile. Paired samples T-test was utilized to analyze responses to therapy. RESULTS: Our cohort consisted of 125 men with hypogonadism and low libido. Mean age was 62 years (± 11.1 years). Serum T levels ranged from 309 ng/dL (baseline, mean value) to 642 ng/dL (3 months after CC initiation, mean value) (p < 0.001). Serum cholesterol levels ranged from 197 to 186 mg/dL (p = 0.003). There were no statistically significant differences when comparing pre and post-treatment HDL-Cholesterol, triglycerides, fasting plasma glucose and prolactin. All men reported improvements in the post-treatment QoL scores. No serious adverse events were recorded. CONCLUSIONS: The CC was effective in stimulating the endogenous production of testosterone. A lower level of total cholesterol was verified after three months of treatment. This medication should be considered as a therapeutic option for some patients with symptomatic male testosterone deficiency.

Análisis preliminar del cuestionario Potenziani para la validación diagnóstica del hipogonadismo de comienzo tardío y su concordancia con los cuestionarios de Heinemann (AMS) y de Morley (ADAM) / Preliminary analysis of the Potenziani questionnaire for the late onset hypogonadism diagnostic validation and its concordance with the Heinemann (AMS) and Morley (ADAM) questionnaires

Hipogonadismo de comienzo tardío, es una condición que afecta 6% al 12% de hombres entre 40 y 70 años y aun así, está subdiagnosticada, por lo que se propone un cuestionario de validación diagnóstica, con el objetivo de lograr mayor sensibilidad, especifidad y predictividad que los cuestionarios ya existentes. Se analizaron 107 hombres entre 45 y 70 años, con disminución del entusiasmo en actividad diaria, cansancio fácil, menor productividad en su trabajo, cambios del humor con propensión a la irritabilidad, disminución de su masa magra muscular, con tendencia al sobrepeso y afectación en actividades recreativas y deportivas. Se hizo interrogatorio exhaustivo, examen físico y pruebas de laboratorio (perfil 20, perfil hormonal urológico masculino, antígeno prostático específico total, libre y relación libre/total, examen de orina y urocultivo). Se solicitó contestar al paciente tres cuestionarios de validación diagnóstica del hipogonadismo de comienzo tardío: Heinemann AMS (Ageing Males Survey-1999, St. Louis University, Androgen Deficiency in Aging Male), Morley ADAM-2000 y el cuestionario de validadción diagnóstica del hipogonadismo de comienzo tardío-Potenziani-2007, para ser comparados y demostrar su validez con pruebas de especificidad y sensibilidad, índice de Youden, pruebas de concordancia con intervalos de confianza del 95%, en relación al diagnóstico bioquímico del hipogonadismo de comienzo tardío. Los resultados arrojaron que el cuestionario "Potenziani" fue más sensible (88,57%), fue más específico (41,67%), tuvo el índice de validez más alto (57,01%) y el valor predictivo positivo más alto de los tres cuestionarios con el 42,5%. Por tal motivo se ha demostrado que el cuestionario propuesto es más adecuado que Heineman-AMS y el Morley-ADAM en la aproximación diagnóstica del síndrome de hipogonadismo de comienzo tardio

Late onset hypogonadism a condition which affect 6%-12% of men between 40-70 years old, and still it is subdiagnosed for which we did a validation questionnaire with the objetive to be more sensitive, especific and predictive that old questionnaires. We analized 107 men with ages between 45-70 years old whom consulted for libido deterioration, erectile dysfunction, less enthusiasm of daily life, less work-productivity, easy tiredness, humor changes with irritability, less muscle mass, overweight, and deterioration of sexual life in general. We performed exhaustive interrogatory, physical examination, and laboratoty test (20 profile, hormonal-urologic profile, prostatic specific antigen, urine and urocultive). We ask them to complete three questionnaires of late onset hypogonadism diagnostic validation: Heinemann AMS, Morley ADAM, Potenziani 2007, to be compared and show its validity with specificity and sensibility tests, Youden Index, test of concordance with confidence interval of 95%, in relation to biochemical diagnosis of deficiency testosterone syndrome. The results were that the Potenziani`s cuestionary was more sensible (88.57%), more specific (41.67%), with the validation index more high (57.01%) and with the positive predictive value more high too (42.5%). For that reason we show that Potenziani`s validation questionnaire of late onset hypogonadism, is more adecuate in the diagnostic aproximation of this condition

Testosterone therapy delays cardiomyocyte aging via an androgen receptor-independent pathway

The testicular feminized (Tfm) mouse carries a nonfunctional androgen receptor (AR) and reduced circulating testosterone levels. We used Tfm and castrated mice to determine whether testosterone modulates markers of aging in cardiomyocytes via its classic AR-dependent pathway or conversion to estradiol. Male littermates and Tfm mice were divided into 6 experimental groups. Castrated littermates (group 1) and sham-operated Tfm mice (group 2, N = 8 each) received testosterone. Sham-operated Tfm mice received testosterone in combination with the aromatase inhibitor anastrazole (group 3, N = 7). Castrated littermates (group 4) and sham-operated untreated Tfm mice (group 5) were used as controls (N = 8 and 7, respectively). An additional control group (group 6) consisted of age-matched non-castrated littermates (N = 8). Cardiomyocytes were isolated from the left ventricle, telomere length was measured by quantitative PCR and expression of p16INK4α, retinoblastoma (Rb) and p53 proteins was detected by Western blot 3 months after treatment. Compared with group 6, telomere length was short (P < 0.01) and expression of p16INK4α, Rb and p53 proteins was significantly (P < 0.05) up-regulated in groups 4 and 5. These changes were improved to nearly normal levels in groups 1 and 2 (telomere length = 0.78 ± 0.05 and 0.80 ± 0.08; p16INK4α = 0.13 ± 0.03 and 0.15 ± 0.04; Rb = 0.45 ± 0.05 and 0.39 ± 0.06; p53 = 0.16 ± 0.04 and 0.13 ± 0.03), but did not differ between these two groups. These improvements were partly inhibited in group 3 compared with group 2 (telomere length = 0.65 ± 0.08 vs 0.80 ± 0.08, P = 0.021; p16INK4α = 0.28 ± 0.05 vs 0.15 ± 0.04, P = 0.047; Rb = 0.60 ± 0.06 vs 0.39 ± 0.06, P < 0.01; p53 = 0.34 ± 0.06 vs 0.13 ± 0.03, P = 0.004). In conclusion, testosterone deficiency contributes to cardiomyocyte aging. Physiological testosterone can delay cardiomyocyte aging via an AR-independent pathway and in part by conversion to estradiol.

Age-related testosterone decline in a Brazilian cohort of healthy military men

INTRODUCTION: Androgen decline in the aging man has become a topic of increasing clinical relevance worldwide, as the reduction in testosterone levels has been reported to be accompanied by loss of muscle mass, accumulation of central adiposity, impaired mobility and increase risk of bone fractures. Although well-established in studies conducted in developed countries, progressive decline in serum testosterone levels with age has been poorly investigated in Brazil. AIM: To determine the pattern of blood testosterone concentrations decline with age in a cohort of Brazilian healthy military men. MATERIALS AND METHODS: We retrospectively reviewed data on serum testosterone measurements of healthy individuals that had undergone a routine check-up at the Military Biology Institute. Blood samples were obtained early in the morning, and total testosterone concentration was determined using a commercial chemoluminescent immunoassay. Mean values were analyzed in five age groups: < 40, 41 to 50, 51 to 60, 61 to 70, and > 70 years. MAIN OUTCOME MEASURE: Mean total testosterone levels. RESULTS: 1,623 subjects were included in the analysis; mean age was 57 years (24 to 87), and mean testosterone level was 575.5 ng/dL (25.0 to 1308.0 ng/dL). The evaluation of age-related changes in total testosterone levels revealed a progressive reduction in serum levels of this hormone with increasing age. Testosterone levels below 300 ng/dL were reported in 321 participants, a prevalence of nearly 20 percent in the study population. CONCLUSION: In agreement with other findings, a reduction of total testosterone levels with age was reported for healthy Brazilian men.

Racial differences in hypogonadal improvement and prostate-specific antigen levels in hypogonadal men treated with testosterone replacement therapy

PURPOSE: To observe hypogonadal men undergoing testosterone replacement therapy (TRT) and assess racial differences in hypogonadal improvement and prostate-specific antigen (PSA) levels. MATERIALS AND METHODS: In a retrospective analysis, 75 hypogonadal men were followed for an average 34 months after initiating TRT. Total testosterone and PSA levels were assessed every 6 months, and patients diagnosed with prostatitis or prostate cancer during treatment were excluded. RESULTS: For 16 African American men, the average age at diagnosis of hypogonadism was 53.5 years, compared with 57.8 years in 59 Caucasian men (p = NS). Pre- and post-treatment testosterone was 219 ng/dL and 310 ng/dL in African American men, and 247 ng/dL and 497 ng/dL in Caucasian men (p = NS). Symptomatic response was 81 percent in African American men and 93 percent in Caucasian men (p = NS). Baseline PSA level was 1.32 ng/mL in African American men and 1.27 ng/mL in Caucasian men, and there was no significant difference in PSA between racial groups at 6-month intervals, although there was a small decreasing trend in the PSA of African Americans compared with Caucasians. CONCLUSIONS: Hypogonadal African American men have a similar normalization of testosterone and symptomatic response as hypogonadal Caucasian men, and PSA levels remain stable over time in both groups. In this hypogonadal cohort, in contrast to studies of eugonadal men, higher PSA levels in African Americans were not observed.

The role of testosterone in type 2 diabetes and metabolic syndrome in men: [review] / O papel da testosterona no diabetes melito tipo 2 e síndrome metabólica em homens: [revisão]

Over the last three decades, it has become apparent that testosterone plays a significant role in glucose homeostasis and lipid metabolism. The metabolic syndrome is a clustering of risk factors predisposing to diabetes mellitus type 2, atherosclerosis and cardiovascular morbidity and mortality. The main components of the syndrome are visceral obesity, insulin resistance, glucose intolerance, raised blood pressure and dyslipidemia (elevated triglycerides, low levels of high-density lipoprotein cholesterol), and a pro-inflammatory and thrombogenic state. Cross-sectional epidemiological studies have reported a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. Lower total testosterone and sex hormone-binding globulin (SHBG) predict a higher incidence of the metabolic syndrome. There is evidence that hypotestosteronemia should be an element in the definition of the metabolic syndrome since low levels of testosterone are associated with or predict the development of the metabolic syndrome and of diabetes mellitus. Administration of testosterone to hypogonadal men reverses part of the unfavorable risk profile for the development of diabetes and atherosclerosis. So far, studies on the effects of normalization of testosterone in hypogonadal men on glucose homeostasis are limited, but convincing, and if diabetes mellitus is viewed in the context of the metabolic syndrome, the present results of testosterone treatment are very encouraging.

Ao longo das últimas três décadas, tornou-se evidente que a testosterona desempenha um papel significativo na homeostase da glicose no metabolismo lipídico. A síndrome metabólica é um agrupamento de fatores de risco que predispõem ao diabetes melito tipo 2, aterosclerose e morbidade e mortalidade cardiovasculares. Os principais componentes da síndrome são: obesidade visceral, resistência insulínica, intolerância à glicose, hipertensão arterial e dislipidemia (triglicerídeos elevados, baixos níveis de HDL-colesterol), além de um estado pró-inflamatório e trombogênico. Estudos epidemiológicos transversais relataram uma correlação direta entre testosterona plasmática e sensibilidade à insulina, e níveis baixos de testosterona se associam com risco aumentado de diabetes tipo 2, ilustrado dramaticamente pela privação androgênica em homens com carcinoma de próstata. Baixos níveis de testosterona total e globulina transportadora de hormônios sexuais (SHBG) predizem maior incidência de síndrome metabólica. Existem agora evidências de que a hipotestosteronemia deveria ser um elemento na definição da síndrome metabólica, uma vez que baixos níveis de testosterona estão associados ou predizem o desenvolvimento de síndrome metabólica e de diabetes melito. A administração de testosterona a homens hipogonádicos reverte parte do perfil desfavorável de risco para o desenvolvimento de diabetes e aterosclerose. Até agora, os estudos relacionados aos efeitos da normalização da testosterona em homens hipogonádicos sobre a homeostase da glicose são limitados, mas convincentes e, se o diabetes melito for visto no contexto da síndrome metabólica, os resultados atuais do tratamento com testosterona são muito encorajadores.

Testosterona sérica e doença cardiovascular em homens: [revisão] / Serum testosterone and cardiovascular disease in men: [review]

As doenças cardiovasculares (DCV) representam atualmente o principal grupo de causa de morte no Brasil. Os homens morrem mais de doença arterial coronariana e possuem níveis mais elevados de testosterona do que as mulheres. No entanto, estudos recentes indicam que os andrógenos podem ter efeito benéfico e/ou neutro no sistema cardiovascular masculino. Baixos níveis de testosterona endógena têm sido relacionados à presença de vários componentes da síndrome metabólica, incluindo dislipidemia, obesidade visceral, hipertensão arterial sistêmica e estados pró-trombóticos. Os dados da relação entre testosterona e reatividade vascular, aterosclerose e mortalidade cardiovascular nos homens são escassos, com os resultados de estudos disponíveis apresentando contradições. Grandes estudos randomizados e prospectivos são necessários para avaliar a função específica dos andrógenos nas DCV masculinas, para que melhores conclusões possam ser estabelecidas.

Cardiovascular diseases (CVD) represent the main cause of death in Brazil. Men die more of coronary artery disease and they have higher levels of testosterone than women. However, recent studies indicate that androgens can have beneficial and/or neutral effect in the male cardiovascular system. Low levels of endogenous testosterone have been involved with the presence of some components of the metabolic syndrome including dyslipidemia, visceral obesity, hypertension and thrombus formation process. Consistent data on the relationship between testosterone and vascular reactivity, atherosclerosis and cardiovascular mortality in men are rare, with the results of available studies presenting contradictions. Large randomized and prospective trials are needed to evaluate androgen-specific function in male CVD so that better conclusions can be established.

Breaking the vicious circle of obesity: the metabolic syndrome and low testosterone by administration of testosterone to a young man with morbid obesity / Quebrando o círculo vicioso da obesidade: síndrome metabólica e baixos níveis de testosterona pela administração de testosterona a um homem jovem com obesidade mórbida

OBJECTIVE: The metabolic syndrome (MS) is associated with low serum testosterone levels. Conversely, low testosterone levels induce MS. These operational mechanisms reinforce one another and induce a vicious cycle. This is a report on a morbid obesity 42 year-old man with the MS and serum testosterone of 5.0 nmol/L (N: 12.0-33.0), who was resistant to treatment with diet and exercise. He was treated with testosterone undecanoate for 16 months. METHODS: Anthropological and laboratory variables were measured before and during testosterone administration. Also the Aging Male Symptom Scale (AMS), the International Index of Erectile Function (IIEF) and Beck's Depression Inventory were assessed. RESULTS: After 16 months, there was a weight loss of 50 kg and a decrease in waist circumference of 36.5 cm. Blood pressure normalized and laboratory variables returned to the normal range. The patient did not meet the criteria for the MS anymore. There were improvements on the AMS, the IIEF and Beck's Depression Inventory. CONCLUSIONS: Normalizing testosterone in men with morbid obesity in combination with diet and exercise, with the MS and low testosterone levels, may rescue them from the MS, improving their mood and their stamina to follow a diet and to exercise.

OBJETIVO: A síndrome metabólica (SM) está associada a baixos níveis séricos de testosterona. Inversamente, baixos níveis de testosterona induzem a SM. Esses mecanismos operacionais se reforçam mutuamente e levam a um círculo vicioso. Este é o relato de um homem de 42 anos, obesidade mórbida com SM e testosterona sérica de 5,0 nmol/L (N: 12,0-33,5), resistente ao tratamento com dieta e exercícios. Ele foi tratado com undecanoato de testosterona por 16 meses. MÉTODOS: Variáveis antropológicas e laboratoriais foram medidas antes e durante a administração de testosterona. Também foram avaliados a Escala de Envelhecimento Masculino (AMS), o Índice Internacional de Função Erétil (IIEF) e a Escala de Beck para Depressão. RESULTADOS: Após 16 meses, houve uma perda de peso de 50 kg e diminuição de 36,5 cm da circunferência abdominal. A pressão arterial foi normalizada e as variáveis laboratoriais também retornaram para os limites de normalidade. O paciente não preenchia mais os critérios para SM. Houve melhoras da AMS, do IIEF e da Escala de Beck para Depressão. CONCLUSÕES: A normalização da testosterona em homens com obesidade mórbida, combinada à dieta e a exercícios, com SM e baixos níveis de testosterona, pode livrá-los da SM, melhorando o humor e o vigor para seguir uma dieta e exercícios.

Uso de andrógeno na menopausa / Androgen use in menopause

As mulheres no climatério, principalmente na pós-menopausa, apresentam redução dos níveis de androgênio - sobretudo da testosterona livre - de aproximadamente 50 por cento, quando comparadas com as de 20 anos. Isso ocorre porque há um acréscimo da testosterona ligada à SHBG, o que a inativa, com a consequente perda da libido, do bem-estar e da energia. A terapia de reposição androgênica se mostra benéfica na medida em que melhora o desejo sexual, a depressão, o aumento de massa magra e o bem-estar. Entretanto, há efeitos colaterais que são correlacionados com as doses e a via de administração. As doses baixas, através das vias periféricas, minimizam acentuadamente esses efeitos. O presente estudo faz uma revisão na literatura das indicações e contraindicações dessa terapia, além de avaliar as formas de administração desses hormônios.

Risk factors for bone loss with prostate cancer in Korean men not receiving androgen deprivation therapy

PURPOSE: Preexisting bone loss in men with prostate cancer is an important issue due to the accelerated bone loss during androgen deprivation therapy (ADT). In addition, a high prostate-specific antigen (PSA) level has been reported to be related to bone metabolism. This study assessed the factors associated with osteoporosis in Korean men with non-metastatic prostate cancer before undergoing ADT. MATERIAL AND METHODS: The study enrolled patients admitted for a prostate biopsy because of a high PSA or palpable nodule on a digital rectal examination. We divided the patients (n = 172) according to the results of the biopsy: group I, non-metastatic prostate cancer (n = 42) and group II, benign prostatic hypertrophy (BPH; n = 130). The lumbar bone mineral density (BMD) was evaluated using quantitative computed tomography. The demographic, health status, lifestyle, body mass index (BMI), serum testosterone concentration, and disease variables in prostate cancer (Gleason score, clinical stage, and PSA) were analyzed prospectively to determine their effect on the BMD. RESULTS: The estimated mean T-score was higher in group I than in group II (-1.96 ± 3.35 vs. -2.66 ± 3.20), but without statistic significance (p = 0.235). The significant factors correlated with BMD in group I were a high serum PSA (ß = -0.346, p = 0.010) and low BMI (ß = 0.345, p = 0.014) in the multiple linear regression model. Also old age (r = -0.481, p = 0.001), a high serum PSA (r = -0.571, p < 0.001), low BMI (r = 0.598, p < 0.001), and a high Gleason’s score (r = -0.319, p = 0.040) were the factors related to BMD in the correlation. The significant factors correlated with BMD in group II were old age (ß = -0.324, p = 0.001) and BMI (ß = 0.143, p = 0.014) in the multiple linear regression model. CONCLUSIONS: The risk factors for osteoporosis in men with prostate cancer include a low BMI, and elevated serum PSA. Monitoring BMD from the outset of ADT is a logical first...

Síndrome de deficiencia de testosterona y su impacto en la salud masculina / Testosterone deficiency syndrome and its impact in adult male pathology

El Síndrome de Deficiencia de Testosterona constituye hoy en día una entidad relevante dentro de las patologías del hombre adulto. Contrariamente a los mitos existentes, la evidencia científica actual demuestra que la Testosterona no sólo está involucrada en el área sexual y reproductiva, sino también en muchos otros sistemas como el cardiovascular, el metabolismo lipídico, la composición corporal, el metabolismo óseo, la función cerebral y el sistema hematopoyético. En todos ellos, su deficiencia puede generar serios efectos que implican un severo impacto en la calidad de vida del hombre mayor. Por otra parte, el conocimiento médico actual permite hoy en día reemplazar esta hormona sin temores. Sabemos que la testosterona no induce la aparición de cáncer de próstata así como también aquellos hombres con testosterona plasmática baja tienen más riesgo de hacer este cáncer así como también más agresivos. El reemplazo hormonal, con la consecuente restauración de los niveles plasmáticos de testosterona genera una mejoría en cada uno de los sistemas afectados lo que finalmente se traduce en una mejoría en la calidad de vida.

The testosterone deficiency syndrome is currently a well established entity amongst adult male pathology. Current evidence demonstrates testosterone involvement not only in sexual and reproductive physiology but also as an active participant in other systems. Cardiovascular system, lipid metabolism, body composition, bone metabolism, brain function and hemathopoyetic system are all severely affected by androgen deficiency. It is well known that testosterone administration does not induce prostate cancer nor it is associated with a higher risk of high grade cancer in the hypogonadic male. Now a days testosterone can be administered without fear. Hormone replacement therapy with normalization of plasmatic testosterone levels is associated with a recovery of all systems affected and consequently an improvement in quality of life.

Andropausa e reposição hormonal no envelhecimento masculino / Andropause and hormone replacement in aging male

Andropausa, ou deficiência androgênica do envelhecimento masculino (DAEM), descreve a entidade clínica definida como uma síndrome associada ao envelhecimento. É uma condição freqüente, mas subdiagnosticada. Os achados são semelhantes àqueles do processo de envelhecimento e incluem perda de energia, depressão, diminuição da libido, disfunção erétil, diminuição da massa e força muscular, osteopenia e osteoporose. Os autores revisam os achados associados com o hipogonadismo tardio, abordam o diagnóstico, as características clínicas e fisiopatológicas da diminuição hormonal, as indicações para reposição hormonal, com suas vantagens e desvantagens, assim como o seguimento destes pacientes.

Andropause or androgenic deficiency of the masculine aging (ADMA) describes a clinical entity which has been defined as a syndrome associated with advanced age. It is a frequent condition but under diagnosed. Symptoms and findings of testosterone deficiency are similar to those associated with aging and include loss of energy, depressed mood, decreased libido, erectile dysfunction, decreased muscle mass and strenght, osteopenia and osteoporosis. This article reviews the findings associated with late hypogonadis, addresses the diagnosis, clinical and pathophysiological features of hormonal decline, the indications for hormone replacement with their disadvantages, as well as the monitoring of these patients.

A study on endocrine changes in patients in intensive care unit.

Pattern of endocrine changes in moderate to severely ill patients in a medical intensive care unit, correlation with the severity of illness and whether these changes can predict outcome of the critically ill patients were evaluated and studied in 80 patients admitted with acute physiology and chronic health evaluation (APACHE) II score >10 and without any pre-existing endocrinopathies or on drugs likely to affect the endocrine axis. Adrenal insufficiency was present in 45%, and mortality was higher in those with lower (<15 microg/dl) and higher (>30 microg/dl) serum cortisol. Sick euthyroid syndrome was detected in 80%, and those with low mean T3 (<0.6 ng/ml), free T4 (<0.89 ng/dl) and total T4 (<4 microg/dl) and had increased mortality. Hypotestosteronaemia was found in 92% of men and was significantly associated with severity of illness in men. Though prolactin is the first hormone to be elevated, there was no correlation between prolactin and severity of illness or mortality.