Improvement in Testosterone Production by Acorus gramineus for the Alleviation of Andropause Symptoms.

Acorus gramineus has a number of beneficial effects, including protective effects against age-related disorders. In this study, the effects of A. gramineus on testosterone production and andropause symptoms were evaluated. We first treated TM3 mouse Leydig cells, responsible for testosterone production, with A. gramineus aqueous extract at different concentrations. In TM3 cells, the testosterone concentration increased in a concentration-dependent manner compared with those in the control. In addition, at 400 µg/mL extract, the mRNA expression level of the steroidogenic enzyme CYP11A1 was increased. Subsequently, 23-week-old Sprague-Dawley (SD) rats exhibiting an age-related reduction in serum testosterone (approximately 80% lower than that in 7-week-old SD rats) were administered A. gramineus aqueous extract for 8 weeks. Serum total testosterone and free testosterone levels were higher and serum estradiol, prostate-specific antigen levels, and total cholesterol levels were lower in the AG50 group (A. gramineus aqueous extract 50 mg/kg of body weight/day) than in the OLD (control group). The AG50 group also showed significant elevations in sperm count, grip strength, and mRNA expression of StAR, CYP11A1, 17ß-HSD, and CYP17A1 compared with those in the OLD group. In conclusion, A. gramineus aqueous extract facilitated steroidogenesis in Leydig cells, elevated testosterone levels, lowered serum estradiol and total cholesterol levels, and increased muscle strength and sperm count, thus alleviating the symptoms of andropause. These findings suggest that A. gramineus aqueous extract is a potentially effective therapeutic agent against various symptoms associated with andropause.

Current Management and Controversies Surrounding Andropause.

Andropause is a condition surrounded by controversies, whether it be through its diagnosis or management. As we learn more about the pathophysiology of hypogonadism, our perspectives on the risks and benefits of testosterone therapy have shifted. We attempt to discuss the most modern and relevant points of controversy currently affecting the field. Throughout this review, we discuss the art of diagnosing hypogonadism as well as the association or lack thereof between testosterone replacement therapy and cardiovascular disease, prostate cancer, thrombosis, antiaging effects, exogenous steroid abuse, and diabetes mellitus.

Menopause, wellbeing and health: A care pathway from the European Menopause and Andropause Society.

This care pathway from the European Menopause and Andropause Society (EMAS) provides an updated pathway for monitoring and guidance of women at midlife, focusing on those approaching the end of the reproductive life-cycle, going through the menopausal transition and beyond. The care pathway is written by professionals involved in women's health and provides a stepwise individualized approach, stratified according to needs, symptoms and reproductive stage. Furthermore, the pathway provides details on screening for chronic diseases related to menopause and ageing. Treatment options for climacteric symptoms range from menopausal hormone therapy to non-hormonal alternatives and lifestyle modifications. Therapy should be tailored to personal needs and wishes. The pathway aims to offer a holistic, balanced approach for monitoring middle-aged women, aiming to control health problems effectively and ensure healthy ageing.

Genistein regulates calcium and phosphate homeostasis without activation of MEK 1/2 signalling pathway in an animal model of the andropause.

Soy isoflavone genistein interplays with numerous physiological or pathophysiological processes during ageing. However, its protective role and underlying mechanisms of action in the regulation of calcium (Ca2+) and phosphate (Pi) homeostasis in an animal model of the andropause are yet to be fully clarified. Wistar male rats (16-month-old) were divided into sham-operated, orchidectomized, orchidectomized estradiol-treated (0.625 mg/kg b.m./day) and orchidectomized genistein-treated (30 mg/kg b.m./day) groups. Treatments were administered subcutaneously for 3 weeks, while the controls received vehicle alone. Estradiol treatment increased the expression level of fibroblast growth factor receptor (FGFR) and parathyroid hormone 1 receptor (PTH1R), and activated mitogen - activated protein kinase kinase 1/2 (MEK 1/2) signaling pathway in the kidneys. Genistein application induced a prominent gene and protein expression of Klotho and downregulated the expression of FGFR and PTH1R in the kidney of andropausal rats. Activation of protein kinase B (Akt) signalling pathway was observed, while MEK 1/2 signaling pathway wasn't altered after genistein treatment. The increase of 25 (OH) vitamin D in the serum and decrease in Ca2+ urine content was observed after genistein application. Our findings strongly suggest genistein as a potent biocompound with beneficial effects on the regulation of Ca2+ and Pi homeostasis, especially during aging process when the balance of mineral metabolism is impaired. These novel data provide closer insights into the physiological roles of genistein in the regulation of mineral homeostasis.

O ambiente inflamatório e os acometimentos de saúde em pessoas em idades relacionadas à menopausa e à andropausa / The inflammatory environment and health involvments in persons in ages related to menopause and andropause

Introdução: O aumento da expectativa de vida da população faz com que as pessoas passem a viver por mais tempo com doenças crônicas não transmissíveis (DCNT). Dentre as mulheres, as fases da vida que mais se destacam pelos acometimentos em saúde são aquelas relacionadas à menopausa; além do risco aumentado para o desenvolvimento da síndrome metabólica (SM), há destaque para os transtornos mentais comuns (TMC) e as doenças articulares (DA). Já entre os homens, uma vez que a andropausa não é tão claramente identificada como a menopausa, acaba-se atribuindo essa ocorrência à idade e às baixas concentrações séricas de testosterona. Todavia, em ambos os sexos, um processo de inflamação sistêmica crônica e de baixo grau (ISBG) tem sido apontado como um importante fator associado ao desenvolvimento e agravo de todas as condições acima mencionadas. A ISBG decorre de alterações próprias do envelhecimento no sistema imune (SI), particularmente a imunossenescência, mas também por outros fatores externos ao SI, em especial as modificações na gordura corporal e no ambiente intestinal. Nesse contexto, estudar a relação e fatores associados a essas condições permite o delineamento de estratégias de intervenção em saúde. Objetivos: Investigar, em pessoas a partir 40 anos de idade, a prevalência e as associações entre desfechos em saúde relacionados a DCNT, incluindo fatores relacionados à ISBG. Métodos: O presente estudo, que consistiu na elaboração de três manuscritos, foi desenvolvido a partir de dados do Inquérito de Saúde de São Paulo de 2015, um estudo transversal, de base populacional e com amostra representativa dos moradores da área urbana do município de São Paulo. No primeiro manuscrito, foi investigada a associação entre a presença de TMC, DA, Índice de massa corporal (IMC) e outras doenças crônicas. As análises incluíram também dados sociodemográficos (idade, escolaridade, raça/etnia); essas associações foram testadas por modelos de regressão logística múltipla. No segundo manuscrito foram testadas as associações entre TMC e DA com o potencial inflamatório da dieta (identificado a partir do cálculo do Índice Inflamatório da Dieta), o nível de atividade física (utilizando o International Physical Activity Questionnaire- IPAq) classificado conforme recomendação da Organização Mundial da Saúde (OMS), a presença de outras doenças crônicas e o IMC. As análises também incluíram variáveis sociodemográficas (faixa etária, escolaridade, raça/etnia). O terceiro manuscrito consistiu em uma subamostra não representativa do banco de dados do estudo ISA, com participantes que tiveram a composição corporal avaliada por DEXA (raios-x de dupla energia), de onde se obteve a massa magra apendicular e o total de gordura corporal. Foi também avaliada a força de preensão manual, que determina a qualidade do músculo esquelético. Foi realizada a dosagem de marcadores inflamatórios (TNF-α) e de permeabilidade intestinal (LPS, zonulina e iFABP). Ainda, esses participantes tiveram realizadas as dosagens de HDL-c plasmático, glicemia de jejum e triacilglicerol, além das medidas de pressão arterial. Esses parâmetros foram utilizados para a classificação da síndrome metabólica (SM). As associações, mediações e direções entre essas variáveis foram testadas a partir de modelos generalizados de equações estruturais. Principais Resultados: Manuscrito 1. A prevalência de TMC entre as mulheres investigadas no estudo esteve entre 26,9% e 38,0%, a de DA ficou entre 18,7% e 31,1%. Foram encontradas associações entre TMC e DA (OR = 1,998; p<0,001), idade entre 56 e 60 anos (OR= 0,542; p=0,018), e a presença de três diagnósticos de outras doenças crônicas não transmissíveis (OR= 2,696; p= 0,027). Manuscrito 2. Avaliando simultaneamente as associações entre TCM, DA, potencial inflamatório da dieta, e o nível de atividade física, observou-se que as associações entre TMC, DA e número de diagnósticos de outras doenças crônicas foram mantidas, e o maior tercil do escore do índice inflamatório da dieta se mostrou positivamente associado a presença de TCM (OR=2,240; p=0,006). O nível de atividade física não apresentou significância, porém permaneceu ajustando os modelos. Manuscrito 3. A síndrome metabólica foi identificada em 45,8% dos participantes, e associações diretas foram observadas entre TNF-α e massa gorda corporal, e entre a permeabilidade intestinal e a massa muscular apendicular. Conclusões: Os resultados aqui apresentados confirmaram uma associação significativa entre transtornos mentais e aspectos inflamatórios, representados pela presença de doenças articulares e outras doenças crônicas, além do potencial inflamatório da dieta. A atividade física mostrou uma associação marginal protetora em relação à inflamação sistêmica e consequentemente aos transtornos mentais. Finalmente, componentes da composição corporal, massa gorda e massa magra apendicular, se mostraram diretamente associados a marcadores inflamatórios e a presença de síndrome metabólica.

Background: The increase in population life expectancy allows individuals to live longer time periods with noncommunicable diseases (NCD). Among women, the life phases that stand out the most by the health compliment are those related to menopause, with emphasis to the common mental disorders (CMD), and the joint diseases (JD), and an increased risk for the metabolic syndrome presentation. Among men, once andropause is not as clearly identified as menopause, the occurrence of these conditions is attributed to age and to the low level of circulating testosterone. The called low-grade systemic inflammation (LGSI) has been pointed as an important factor associated to the development and worsening of all the mentioned conditions. The LGSI results from the immune system (IS) proper alterations, but also from factor aside IS, especially the body fat and gut environment changes. In this context, investigating the relations and factors associated to those conditions allows designing health intervention strategies. Aims: To investigate, in persons aged 40+ years old, the prevalence and associations between CMD related outcomes, with emphasis on the factors associated to the LGSI. Methods: The present study, which is constituted of three manuscript elaboration, was developed from data of the 205 Health Survey of São Paulo, a population-based cross-sectional study, with representative sample of urban residents of the city of São Paulo. In the first manuscript, associations of CMD, JD, and other chronic conditions, and body mass index (BMI), were investigated. The analysis also included sociodemographic data (age, schooling, race/ethnicity); these associations were testes by multiple logistic regression models. In the second manuscript, associations were tested between CMD and JD, with the inflammatory potential of the diet (identified from the Dietary Inflammatory Index calculation), the leisure physical activity level [classified according to WHO (World Health Organization) proposition using the International Physical Activity Questionnaire- IPAq], the presence of other chronic conditions and BMI. Analysis also included sociodemographic variables (age intervals, schooling, race/ethnicity). Third manuscript consisted of a sub-sample, which was not representative of the Health Survey of São Paulo, with participants who had their body composition evaluated by DXA (dual energy x-ray), from which appendicular muscle mass and total body fat were obtained. Also, handgrip strength, that determinate skeletal muscle quality, was evaluated. Inflammatory (TNF-α) and gut permeability (LPS, zonulin and iFABP) were evaluated. Yet, these participants had plasmatic HDL-c, fasting blood glucose and triacylglycerol, and arterial blood pressure evaluated. These parameters were used for the metabolic syndrome (MS) classification. Associations, mediations, and directions among those variables were tested by Generalized Structural Equation Models. Main results: Manuscript 1. The prevalence of CMD among investigated women was found between 26.9% and 38.0%, and from 18.7% to 31.1% for JD. Associations were found between CMD and DA (OR= 1.998; p<0.0001), age from 56 to 60 years old (OR= 0.542; p=0,018), and the presence of the diagnostics of three chronic conditions other than JD (OR= 2.696; p=0.027). Manuscript 2. Simultaneously evaluating the associations between CMD, JD, and dietary inflammatory potential, physical activity level, and the number of other chronic conditions diagnosis, and the higher dietary inflammatory index score presented positively associated to the presence of CMD (OR= 2.240; p=0.006). Physical activity level did not present significant associations, but it adjusted the models. Manuscript 3. Metabolic Syndrome was identified in 45.8% of the participants, and direct associations were observed between TNF-α and body fat mass, and from gut permeability and the appendicular muscle mass. Conclusions: The here presented results confirm a significant association between common mental disorders and inflammatory aspects, represented by the presence of joint diseases and other chronic conditions, and also the dietary inflammatory potential. Physical activity presented marginal protective association in relation to systemic inflammation, and consequently to common mental disorders. Finally, body composition components, body fat and appendicular muscle mass, were directly associated to inflammatory markers and to the presence of metabolic syndrome.

El climaterio como etapa fisiológica crucial en la prevención de la enfermedad cardiovascular / The climacteric as a crucial physiological stage in the prevention of cardiovascular disease

El climaterio es una etapa fisiológica que permite al médico reconocer tempranamente los riesgos de patologías y la gran oportunidad de revertirlas. Este trabajo examinará la evidencia actual de la terapia hormonal en la prevención primaria de la enfermedad cardiovascular en mujeres, así como la importancia que igualmente tienen la indemnidad de los ovarios, el peso normal, el uso correcto de antibióticos, la preservación de la microbiota intestinal, las dietas antioxidantes, los estilos de vida saludables y el obligatorio abandono del hábito de fumar.

Soy isoflavone-caused shunting of the corticosteroidogenesis pathways in andropausal subjects: Top-down impulse for the optimal supplementation design.

In a series of our previous works, we revealed the beneficial effects of applied soy isoflavones (genistein or daidzein) on the wide context of corticosteroidogenesis in vivo, in a rat model of the andropause. Soy isoflavones decreased the circulating levels of pituitary adrenocorticotropic hormone, inhibited aldosterone secretion, as well as corticosterone production and secretion, but stimulated dehydroepiandrosterone secretion, all in andropausal rats. In vitro studies indicate that the mechanism underlying these hormonal changes relies on inhibition of the pituitary tyrosine kinase and adrenocortical 3ß-hydroxysteroid dehydrogenase enzymes by soy isoflavones. Although the clinical studies are in their infancy, the opinion is that genistein and daidzein have therapeutic potential for the safe treatment of ageing-caused androgen deprivation and glucocorticoid excess with related metabolic/hemodynamic issues in males. Our accumulated experience and knowledge in the field of biomedical effects of plant polyphenols have provided a platform for potential recommending the agenda to organize and accelerate experimental research aimed at producing the optimal supplementation. We hypothesize that an in vivo approach should first be exploited in the sequence of investigative steps, followed by in vitro studies and synchronously conducted molecular docking analyses. In vivo research, besides establishing the margin of exposure safety or adjustment of the correct polyphenol dose, enables identification and quantification of the metabolites of applied polyphenols in the blood. Subsequent in vitro exploitation of the metabolites and related docking analyses provide clarification of the molecular mechanisms of action of applied polyphenols. Chemical modification of the polyphenol structure or coupling it with nanoparticles might be the next step in optimizing the design of supplementation. Selected, intact or chemically-modified polyphenol molecules should be included in preclinical studies on a more closely-related species, while clinical studies would finally assess the safety and effectiveness of a polyphenol-based remedial strategy. The final supplement represents a product of an appropriate technological process, conducted in accordance with the recommendations derived from the preceding research.

European Menopause and Andropause Society (EMAS) and International Gynecologic Cancer Society (IGCS) position statement on managing the menopause after gynecological cancer: focus on menopausal symptoms and osteoporosis.

INTRODUCTION: Worldwide, it is estimated that about 1.3 million new gynecological cancer cases are diagnosed each year. For 2018, the predicted annual totals were cervix uteri 569,847, corpus uteri 382,069, ovary 295,414, vulva 44,235 and va​gina 17,600. Treatments include hysterectomy with or without bilateral salpingo-oophorectomy, radiotherapy and chemotherapy. These can result in loss of ovarian function and, in women under the age of 45, early menopause. AIM: The aim of this position statement is to set out an individualized approach to the management, with or without menopausal hormone therapy, of menopausal symptoms and the prevention and treatment of osteoporosis in women with gynecological cancer. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: The limited data suggest that women with low-grade, early-stage endometrial cancer may consider systemic or topical estrogens. However, menopausal hormone therapy may stimulate tumor growth in patients with more advanced disease, and non-hormonal approaches are recommended. Uterine sarcomas may be hormone dependent, and therefore estrogen and progesterone receptor testing should be undertaken to guide decisions as to whether menopausal hormone therapy or non-hormonal strategies should be used. The limited evidence available suggests that menopausal hormone therapy, either systemic or topical, does not appear to be associated with harm and does not decrease overall or disease-free survival in women with non-serous epithelial ovarian cancer and germ cell tumors. Caution is required with both systemic and topical menopausal hormone therapy in women with serous and granulosa cell tumors because of their hormone dependence, and non-hormonal options are recommended as initial therapy. There is no evidence to contraindicate the use of systemic or topical menopausal hormone therapy by women with cervical, vaginal or vulvar cancer, as these tumors are not considered to be hormone dependent.

European Menopause and Andropause Society (EMAS) and International Gynecologic Cancer Society (IGCS) position statement on managing the menopause after gynecological cancer: focus on menopausal symptoms and osteoporosis.

Worldwide, it is estimated that about 1.3 million new gynecological cancer cases are diagnosed each year. For 2018, the predicted annual totals were cervix uteri 569 847, corpus uteri 382 069, ovary 295 414, vulva 44 235, and va​gina 17 600. Treatments include hysterectomy with or without bilateral salpingo-oophorectomy, radiotherapy, and chemotherapy. These can result in loss of ovarian function and, in women under the age of 45 years, early menopause. The aim of this position statement is to set out an individualized approach to the management, with or without menopausal hormone therapy, of menopausal symptoms and the prevention and treatment of osteoporosis in women with gynecological cancer. Our methods comprised a literature review and consensus of expert opinion. The limited data suggest that women with low-grade, early-stage endometrial cancer may consider systemic or topical estrogens. However, menopausal hormone therapy may stimulate tumor growth in patients with more advanced disease, and non-hormonal approaches are recommended. Uterine sarcomas may be hormone dependent, and therefore estrogen and progesterone receptor testing should be undertaken to guide decisions as to whether menopausal hormone therapy or non-hormonal strategies should be used. The limited evidence available suggests that menopausal hormone therapy, either systemic or topical, does not appear to be associated with harm and does not decrease overall or disease-free survival in women with non-serous epithelial ovarian cancer and germ cell tumors. Caution is required with both systemic and topical menopausal hormone therapy in women with serous and granulosa cell tumors because of their hormone dependence, and non-hormonal options are recommended as initial therapy. There is no evidence to contraindicate the use of systemic or topical menopausal hormone therapy by women with cervical, vaginal, or vulvar cancer, as these tumors are not considered to be hormone dependent.

Daidzein upregulates anti-aging protein Klotho and NaPi 2a cotransporter in a rat model of the andropause.

In a rat model of the andropause we aimed to examine the influence of daidzein, soy isoflavone, on the structure and function of parathyroid glands (PTG) and the expression levels of some of the crucial regulators of Ca2+ and Pi homeostasis in the kidney, and to compare these effects with the effects of estradiol, serving as a positive control. Middle-aged (16-month-old) male Wistar rats were divided into the following groups: sham-operated (SO), orchidectomized (Orx), orchidectomized and estradiol-treated (Orx+E; 0.625mg/kg b.w./day, s.c.) as well as orchidectomized and daidzein-treated (Orx+D; 30mg/kg b.w./day, s.c.) group. Every treated group had a corresponding control group. PTH serum concentration was decreased in Orx+E and Orx+D groups by 10% and 21% (p<0.05) respectively, in comparison with the Orx. PTG volume was decreased in Orx+E group by 16% (p<0.05), when compared to the Orx. In Orx+E group expression of NaPi 2a was lower (p<0.05), while NaPi 2a abundance in Orx+D animals was increased (p<0.05), when compared to Orx. Expression of PTH1R was increased (p<0.05) in Orx+E group, while in Orx+D animals the same parameter was decreased (p<0.05), in comparison with Orx. Klotho expression was elevated (p<0.05) in Orx+D rats, in regard to Orx. Orx+D induced reduction in Ca2+/creatinine and Pi/creatinine ratio in urine by 32% and 16% (p<0.05) respectively, in comparison with Orx. In conclusion, presented results indicate the more coherent beneficial effects of daidzein compared to estradiol, on disturbed Ca2+ and Pi homeostasis, and presumably on bone health, in the aging male rats.

MR-10 Enhances Men's Health by Improving Endogenous Male Sex Hormone Generation.

Although there is a clear need for improving men's health, treatment with suitable natural substances has not yet been well established. Previously, it was reported that MR-10, a novel complex of Korean dandelion and rooibos found by screening many natural products, improved sperm generation and activity. Here, the ability of MR-10 to increase testosterone levels and enhance men's health was tested. Treatment with MR-10 (400 mg/day) for a month significantly increased levels of free testosterone, total testosterone, and the testosterone precursor dehydroepiandrosterone by 22%, 14%, and 32%, respectively, in clinical studies. Also, men's health in terms of mental, physical, and sexual aspects, as determined by using the clinical questionnaires Androgen Deficiency of Aging Men and Aging Males' Symptoms, was improved. Furthermore, the safety of MR-10 was determined by testing levels of prostate-specific antigen, glutamic oxaloacetic transaminase, and glutamic pyruvate transaminase; and the lack of changes due to MR-10 treatment supports the safety of MR-10. In conclusion, this study suggests that MR-10 is a safe and effective natural product improving men's sexual health.

Treinamento funcional em homens com deficiência androgênica / Functional training in men with androgen deficiency

Os sintomas da deficiência androgênica durante o envelhecimento masculino (DAEM) são eviden-ciados, a partir dos 40 anos, sendo que a atividade física (AF) pode atenuar esse processo. O objetivo desse estudo foi analisar a influência de um protocolo de treinamento funcional na AF habitual em homens com DAEM. Participaram 20 homens de 40 a 59 anos (média de idade de 49,63 ± 4,65 anos), sendo 11 do grupo experimental e nove do grupo controle. Foram coletadas informações por meio de um questionário autoaplicável, dividido em três seções: características gerais e clínicas; AF ­ IPAQ (versão curta) e sintomas do envelhecimento masculino pela "Aging Male Symptoms Scale (AMS)". Na análise dos dados, utilizou-se a estatística descritiva (média, desvio padrão e frequência simples) e inferencial (Exato de Fisher e Anova two way com medidas repetidas com teste de com-paração de Sydak). O grupo experimental apresentou um aumento médio significativo no tempo de caminhada, em minutos por semana (265 ± 53 minutos; p = 0,013), atividades moderadas (138 ± 21 minutos; p = 0,004), moderadas + vigorosas (209 ± 24 minutos; p < 0,001) e total (474 ± 48 minutos; p < 0,001) em comparação ao grupo controle. Um protocolo de treinamento funcional e a motivação da prática de AF foi eficaz para o aumento do tempo de prática de AF em homens com DAEM

The symptoms of androgen deficiency in the aging male (ADAM) affect men from the age of 40, and in this context it is noted that the practice of physical activity (PA) can help in this process. Thus, the objective of this non-randomized clinical trial was to analyze the influence of a functional training protocol on habitual PA in men with ADAM. Twenty men aged 40 to 59 years (mean age 49,63 ± 4,65 years) 11 of the exper-imental group and 9 of the control group. Data were collected through a self-administered questionnaire divided into three sections: sociodemographic and clinical characteristics; Physical activity - IPAQ (short version) and symptoms of male aging by aging male symptoms scale (AMS); In which men responded in the pre and post-intervention, after being allocated into experimental and control groups. Statistical analysis was descriptive (mean, standard deviation and simple frequency) and inferential (Fisher exact, Anova two way tests with repeated measurements and Sydak comparison test). The experimental group presented a significant mean increase in walking time, in minutes per week (265 ± 53 minutes, p = 0.013), moderate (138 ± 21 minutes, p = 0.004), moderate + vigorous activities (209 ± 24 minutes; p <0.001) and total (474 ± 48 minutes, p < 0.001) compared to the control group. A functional training protocol and motivation for the practice of PA was effective for increasing the practice of AF in men with DAEM

Does long-term androgen deficiency lead to metabolic syndrome in middle-aged rats?

Evidence from clinical observational studies and animal experiments suggests that hypogonadism is associated with the metabolic syndrome. In most of the experiments, androgen deficiency is induced by gonadectomy in the adulthood and relatively short-term effects of hypogonadism on metabolic parameters are usually observed. The purpose of this study was to evaluate the metabolic effects of long-term androgen deficiency starting before puberty in middle-aged male rats. The components of the metabolic syndrome were examined in male, female and gonadectomized male rats at the age of 18months. Sex differences were observed in plasma testosterone, cholesterol, high-density lipoproteins and also in body weight and in glycemia dynamics during oral glucose tolerance test. Gonadectomy and long-term hypogonadism did not affect most of the analyzed metabolic parameters such as blood pressure, glycemia, plasma insulin and uric acid. The only exception was the significantly higher liver enzymes in plasma and triacylglycerol in liver found in gonadectomized males. Except low-density lipoprotein, neither treatment of middle-aged males and females with letrozole, nor supplementation of estradiol as the metabolite of testosterone in gonadectomized male rats changed any of the observed metabolic parameters. Our results suggest that long-term hypogonadism started before puberty does not induce metabolic syndrome in middle-aged male rats, but may affect the liver. Sex differences in metabolic parameters in middle-aged rats are not mediated by testosterone. Whether hypogonadism predispose to metabolic syndrome in combination with other risk factors needs further clarification.

Novel aryl piperazines for alleviation of 'andropause' associated prostatic disorders and depression.

A series of seventeen piperazine derivatives have been synthesized and biologically evaluated for the management of andropause-associated prostatic disorders and depression. Five compounds 16, 19, 20, 21 and 22 significantly inhibited proliferation of androgen-sensitive LNCaP prostatic cell line with EC50 values of 12.4 µM, 15.6 µM, 11.8 µM, 10.4 µM, 12.2 µM respectively and decreased Ca2+ entry through adrenergic-receptor α1A blocking activity. Anti-androgenic behaviour of compound 19 and 22 was evident by decreased luciferase activity. The high EC50 value in AR-negative cells PC3 and DU145 suggested that the cytotoxicity of compounds was due to AR down regulation. Compound 19 reduced the prostate weight of rats by 53.8%. Further, forced-swimming and tail-suspension tests revealed antidepressant-like activity of compound 19, lacking effects on neuromuscular co-ordination. In silico ADMET predictions revealed that the compound 19 had good oral absorption, aqueous solubility, non-hepatotoxic and good affinity for plasma protein binding. Pharmacokinetic and tissue uptake of 19 at 10 mg/kg demonstrated an oral bioavailability of 35.4%. In silico docking studies predicted similar binding pattern of compound 19 on androgen receptor as hydroxyflutamide. Compound 19 appears to be a unique scaffold with promising activities against androgen associated prostatic disorders in males like prostate cancer and BPH and associated depression.

Nivel de información sobre el síndrome de declinación de la función testicular en el envejecimiento masculino / Level of information on the declining testicular function syndrome in male aging

Introducción: el síndrome de declinación de la función testicular del hombre que envejece ha cobrado relevancia reciente, pero se asume que se conoce poco. Objetivo: identificar el nivel de información, en población y proveedores de salud, sobre este síndrome. Métodos: estudio descriptivo transversal, que involucró a 452 personas de población general, 109 médicos especialistas afines al tema y 406 de atención primaria. Se emplearon cuestionarios autoadministrados, estadísticas descriptivas y prueba chi2. Resultados: de la muestra poblacional 70,30 por ciento de las mujeres y 56,0 por ciento de los hombres reconocieron que el hombre experimenta un proceso equivalente al climaterio femenino; 64,04 por ciento no conocía los síntomas y 47,12 por ciento de los hombres mayores de 40 años señalaron edad de comienzo superior a la suya. De los especialistas afines, solo 10 habían oído hablar de todos los términos que se emplean para referirse al síndrome, 77,06 por ciento habían escuchado frecuentemente andropausia y 70,65 por ciento climaterio masculino; 27,52 por ciento dio definiciones incorrectas. De atención primaria, 28,57 por ciento no reconoció ningún término, 21,18 por ciento había escuchado frecuentemente andropausia y 19,95 por ciento climaterio masculino; 51,7 por ciento no definió correctamente el síndrome. El 74,14 por ciento no mencionó síntomas, 76,85 por ciento señaló contraindicaciones excesivas al tratamiento y 85,22 por ciento valoró su conocimiento como insuficiente. El nivel de información no se relacionó con edad, sexo o tiempo de graduado (p> 0,05). Conclusiones: la población, principalmente las mujeres, reconoce el síndrome, pero no domina sus manifestaciones. En médicos, con independencia de la edad, sexo o tiempo de graduado, la información se limita mayoritariamente a términos como andropausia y climaterio masculino; el dominio conceptual, del cuadro clínico y tratamiento, es insuficiente(AU)

Introduction: declining testicular function syndrome of the aging man has gained recent relevance but it is accepted that little is known about it. Objective: to find out the level of information of the population and of the health providers on this syndrome. Methods: cross-sectional and descriptive study involving 452 people from the general population, 109 medical specialists related to this topic and 406 primary care physicians. Self-administered questionnaires, summary statistics and chi-square test were all used. Results: in the population sample, 70.30 percent of women and 56 percent of men admitted that man experiences a process similar to the female climaterium; 64.04 percent did not know the symptoms and 47.12 percent of men older than 40 years stated that this process occurred at an age above that of theirs. As to the related specialists, just 10 had heard about all the terms used to mention this syndrome, 77.06 percent had often heard the term andropause and 70.65 percent the term male climaterium, and 27.52 percent gave incorrect definitions. In the primary health care physician group, 28.57 percent did not recognize any term, 21.18 percent had frequently heard about andropause and 19.95 percent about male climaterium, and 51.7 percent did not give a correct definition of the syndrome. In the sample 74.14 percent did not mention any symptom, 76.85 percent pointed out excessive treatment contraindications and 85.22 percent assessed their knowledge as poor. The level of information was not associated to age, sex or time of graduation (p> 0.05). Conclusions: the population, mainly women, recognizes the syndrome but did not know well the symptoms. Regardless of age, sex or time of graduation, the physicians' information about the syndrome is mostly limited to terms such as andropause and male climaterium but they did not master the concept, the clinical picture or the treatment(AU)

Sintomas do envelhecimento masculino relacionados à atividade física e qualidade de vida_uma revisão sistemática / Aging male symptoms related to physical activity and quality of life: a systematic review

O objetivo desta revisão foi identificar artigos originais que relacionam a sintomatologia do envelhecimento masculino com a qualidade de vida e a atividade física. Esta revisão seguiu as recomendações do Preferred reporting items for Systematic Reviews and Meta-análise (PRISMA). Foram selecionados artigos de bases de dados Medline/PubMed, LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde), e das biliotecas eletrônicas SciELO (Scientific Electronic Library Online) e Portal Periódicos da Capes, publicados nos últimos dez anos (janeiro de 2003 a fevereiro de 2013), em português, inglês e espanhol. As palavras-chaves utilizadas foram: atividade física, qualidade de vida e andropausa ou sintomas do envelhecimento masculino, presentes no título ou nos resumos dos artigos. Utilizou-se a escala proposta por Downs e Black, para avaliação metodológica dos artigos incluídos na revisão. Identificou-se 233 estudos; 43 preencheram os critérios de inclusão. A maior parte dos estudos foi realizado em países da Europa, para análise das variáveis utilizou-se medidas indiretas como questionários, medidas diretas e coleta sanguínea. Em 18 estudos relatou-se presença de sintomas do envelhecimento masculino; em cinco deles descreveu-se que a qualidade de vida foi afetada pelos sintomas. Apenas três estudos relacionaram a sintomatologia com a atividade física. Os sintomas do envelhecimento masculino podem estar associados a diferentes fatores, influenciando os todos domínios da qualidade de vida dos homens, sendo os sintomas sexuais os mais frequentes, seguidos dos somáticos e psicológicos. Embora a atividade física seja relatada como benéfica, neste período foram encontrados poucos estudos, havendo necessidade de pesquisas que relacionem essas variáveis...(AU)

The aim of this review was to identify original articles that relate the aging male symptoms with quality of life and physical activity. This review followed the reporting items Preferred recommendations for Systematic Reviews and Meta-analysis (PRISMA). Were selected articles from databases Medline / PubMed, LILACS (Latin American and Caribbean Health Sciences), and electronic biliotecas SciELO (Scientific Electronic Library Online) and Portal Journals Capes, published in the last ten years (January 2003 to February 2013), in Portuguese, English and Spanish. The key words used were: physical activity, quality of life and andropause or aging male symptoms, present in the title or summary of articles. Were used the scale Proposed by Downs and Black for methodological evaluation of the articles included in the review. It identified 233 studies; 43 met the inclusion criteria. Most studies were conducted in countries of Europe, to analyze the variables were used indirect measures such as questionnaires, direct measurements and blood collection. In 18 studies it was reported the presence of aging male symptoms; in five of them it has been described that the quality of life was affected by symptoms. Only three studies have related symptoms with physical activity. The aging male symptoms may be associated with different factors, influencing all domains of quality of life. The sexual symptoms were the most frequent, followed by somatic and psychological. Although physical activity is reported to be beneficial in this period, few studies have been found...(AU)

Traumatic andropause after combat injury.

In association with lower extremity amputation, complex genitourinary injuries have emerged as a specific challenge in modern military trauma surgery. Testicular injury or loss has profound implications for the recovering serviceman, in terms of hormone production and future fertility. The initial focus of treatment for patients with traumatic testicular loss is haemostasis, resuscitation and management of concurrent life-threatening injuries. Multiple reoperations are commonly required to control infection in combat wounds; in a review of 300 major lower extremity amputations, 53% of limbs required revisional surgery, with infection the commonest indication. Atypical infections, such as invasive fungal organisms, can also complicate military wounding. We report the case of a severely wounded serviceman with complete traumatic andropause, whose symptomatic temperature swings were initially mistaken for signs of occult sepsis.

The endocrine dyscrasia that accompanies menopause and andropause induces aberrant cell cycle signaling that triggers re-entry of post-mitotic neurons into the cell cycle, neurodysfunction, neurodegeneration and cognitive disease.

This article is part of a Special Issue "SBN 2014". Sex hormones are physiological factors that promote neurogenesis during embryonic and fetal development. During childhood and adulthood these hormones support the maintenance of brain structure and function via neurogenesis and the formation of dendritic spines, axons and synapses required for the capture, processing and retrieval of information (memories). Not surprisingly, changes in these reproductive hormones that occur with menopause and during andropause are strongly correlated with neurodegeneration and cognitive decline. In this connection, much evidence now indicates that Alzheimer's disease (AD) involves aberrant re-entry of post-mitotic neurons into the cell cycle. Cell cycle abnormalities appear very early in the disease, prior to the appearance of plaques and tangles, and explain the biochemical, neuropathological and cognitive changes observed with disease progression. Intriguingly, a recent animal study has demonstrated that induction of adult neurogenesis results in the loss of previously encoded memories while decreasing neurogenesis after memory formation during infancy mitigated forgetting. Here we review the biochemical, epidemiological and clinical evidence that alterations in sex hormone signaling associated with menopause and andropause drive the aberrant re-entry of post-mitotic neurons into an abortive cell cycle that leads to neurite retraction, neuron dysfunction and neuron death. When the reproductive axis is in balance, gonadotropins such as luteinizing hormone (LH), and its fetal homolog, human chorionic gonadotropin (hCG), promote pluripotent human and totipotent murine embryonic stem cell and neuron proliferation. However, strong evidence supports menopausal/andropausal elevations in the LH:sex steroid ratio as driving aberrant mitotic events. These include the upregulation of tumor necrosis factor; amyloid-ß precursor protein processing towards the production of mitogenic Aß; and the activation of Cdk5, a key regulator of cell cycle progression and tau phosphorylation (a cardinal feature of both neurogenesis and neurodegeneration). Cognitive and biochemical studies confirm the negative consequences of a high LH:sex steroid ratio on dendritic spine density and human cognitive performance. Prospective epidemiological and clinical evidence in humans supports the premise that rebalancing the ratio of circulating gonadotropins:sex steroids reduces the incidence of AD. Together, these data support endocrine dyscrasia and the subsequent loss of cell cycle control as an important etiological event in the development of neurodegenerative diseases including AD, stroke and Parkinson's disease.

Are andropause symptoms related to depression?

BACKGROUND: Andropause is a middle-age condition in which men experience changes in their physical, spiritual and emotional health. The association between andropause and psychological symptoms such as depression are not very clear yet. AIMS: The objective of this study was therefore to determine the association between the 'Aging Males Symptoms Scale' (AMS) and depression. METHODS: A cross sectional study was conducted among 521 old men. To collect data, the AMS and the Patient Health Questionnaires 2 and 9 were used to screen depression, in addition to questions on background and fertility. Multiple linear regression analysis was used to assess the association between andropause symptoms and depression. RESULTS: Based on our results and the AMS score, 51.5% of the study population had clinical symptoms of androgen disorder, 3.7% of which had severe symptoms. There was a strong correlation between the AMS score and depression. Depression, diabetes, cigarette smoking and spousal age retained their significant associations even after entering the relevant demographic, anthropometric, smoking and disease variables in the multivariable model. As a positive predictive factor, depression had the strongest association with AMS. CONCLUSIONS: Based on our results, there is a direct association between andropause symptoms and depression, where the increasing AMS score corresponds with the severity of depression. DISCUSSION: Our results show the need of screening for depression when evaluating andropause symptoms.