Visceral obesity,androgens and the risks of cardiovascular disease and diabetes mellitus

The sex difference in cardiovascular morbidity is traditionally ascribed to the effects of testosterone on the lipid profile. Epidemiological studies show, however, that men with cardiovascular disease have low rather than high circulating testosterone. The factor responsible for both the higher prevalence of cardiovascular disease and the low testosterone might be visceral obesity. Men and women differ in their pattern of fat distribution. Women have predominantly gluteofemoral fat depots and men preferential abdominal/visceral depots. In puberty testosterone favors abdominal/visceral fat deposition. Visceral fat has a high metabolic turnover and the free fatty acids drain on the portal vein. With a large visceral fat depot the liver is flooded with free fatty acids inducing high levels of triglycerides and low high-density lipoprotein cholesterol, impairment of insulin metabolism and reducing insulin sensitivity. These factors contribute to the development of cardiovascular disease and diabetes type II. High insulin levels suppress sex hormone-binding globulin thus lowering circulating testosterone. The fat cell produces leptin signalling to the brain to reduce food intake and increase energy expenditure. High leptin levels suppress testosterone. Some studies suggest that testosterone supplementation reduces visceral obesity and improves cardiovascular risks but more evidence is needed.     

Why can patients with erectile dysfunction be considered lucky? The association with testosterone deficiency and metabolic syndrome

Metabolic syndrome (MetS) is a diagnostic category, based on a cluster of risk factors (hyperglycemia/diabetes, abdominal obesity, hypertriglyceridaemia, low HDL cholesterol and hypertension), which identifies subjects at high risk for forthcoming type 2 diabetes mellitus and cardiovascular (CV) diseases. Recently, a close association between MetS, erectile dysfunction (ED) and male hypogonadism has been reported. In patients with MetS, hypogonadism can exacerbate sexual dysfunction and arteriogenic ED because of its typical symptoms, such as decreased sexual desire and mood disturbances. On the other hand, hypogonadism per se has been associated with an increased risk of CV and overall mortality. Obesity and in particular central obesity is nowadays considered the most important determinant of MetS-induced hypogonadism whereas hypertension and diabetes play a major role in ED associated with MetS. This review analyses the current literature regarding the relationship between ED, MetS and hypogonadism emphasising the epidemiological and psychopathological aspects and stressing the concept that ED subjects are ‘lucky’, because ED offers a unique chance to undergo medical examination and therefore to improve not only their sexual but, most importantly, their overall health.     

Testosterone deficiency and the metabolic syndrome

Evidence is presented to link components of the metabolic syndrome to testosterone deficiency and obesity. Testosterone deficiency in hypogonadism or testosterone deprivation in normo-gonadotropic men increases fat mass as well as fasting insulin levels. Testosterone supplementation (TS) in a dose dependent manner, increase lean body mass (LBM), reduces fat mass, body mass index (BMI) and waist hip ratio in both young and elderly hypogonadal men. A negative association between T and insulin resistance as well as impaired glucose intolerance has been demonstrated and in type 2 diabetic men TS improves metabolic parameters. TS improves most components of the metabolic syndrome and also reduces inflammatory cytokines.     

Association of general and abdominal obesity with age,endocrine and metabolic factors in Asian men

Objective: This study made use of the percent abdominal fat to define abdominal obesity (AbO) and examined the differential associations of general obesity (GOb) and AbO with age, metabolic and endocrine factors.

Methods: Metabolic, endocrine and anthropometric factors and body composition were measured in 481 Asian men.

Results: A DEXA-derived ≥25% abdominal fat (PAbdF) was used to define men with AbO. Age was directly associated with PAbdF and percent total body fat (PBF). Exercise intensity was negatively associated with PBF. Both PBF and PAbdF were associated with HDL and LDL, but have opposite correlation with triglyceride. Furthermore, both PBF and PAbdF were associated with the number of metabolic syndrome (MetS) risk factors. Men with GOb had lower levels of percent lean mass (PLM), testosterone and bioavailable testosterone, and higher insulin and glucose levels. Men with AbO had lower arm and leg fat, higher insulin levels and triglycerides.

Conclusions: Men with GOb and AbO had different pattern of body composition. Age may be a contributory factor in AbO and a sedentary lifestyle may contribute to GOb. Both GOb and AbO are associated with an increased risk of MetS, with GOb more predispose to risk of diabetes, while AbO more at risk for cardiovascular diseases.     

Metabolic syndrome and the menopause

The metabolic syndrome consists of a combination of risk factors that include abdominal obesity, atherogenic dyslipidaemia, hypertension and insulin resistance. It increases the risk of cardiovascular disease and type 2 diabetes. The increased risk of cardiovascular disease is higher in women than in men. The first manifestation of metabolic syndrome may occur in pregnancy presenting as gestational diabetes or preeclampsia. Both conditions are associated with increased insulin resistance. Also metabolic syndrome is more common in polycystic ovarian syndrome. It has been suggested that there is a metabolic syndrome resulting from the menopause due to estrogen deficiency, as many of the risk factors are more prevalent in postmenopausal women. Also estrogen replacement improves insulin sensitivity and reduces the risk of diabetes. The key elements in managing the metabolic syndrome are weight reduction, increasing physical activity and diet modification. If blood pressure, lipid and glycaemic control are not achieved through these interventions then pharmacological therapy will be required.     

Epidemiology and risk factors of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction

Benign prostatic hyperplasia (BPH) is very common in aging men and causes lower urinary tract symptoms (LUTS), which decrease health-related quality of life. A number of evidence suggests that other than ageing, modifiable factors, such as increasing prostate volume, obesity, diet, dyslipidemia, hormonal imbalance, hypertension, metabolic syndrome, alcohol, and smoking, also contribute to the development of BPH and/or LUTS. More recently, erectile dysfunction (ED) has been linked to LUTS/BPH as a part of this syndrome, suggesting that patients with BPH or LUTS easily develop ED, and that LUTS/BPH symptoms often coexist with ED. This article focuses on the epidemiology and risk factors of the combined phenotype LUTS/BPH – ED.     

Increased visceral adiposity index associated with sexual dysfunction in men

Objective: Visceral adipose index (VAI) is a novel parameter for the evaluation of visceral obesity. As we know that obesity is a risk factor for erectile dysfunction (ED). So, in this study, we compared the VAI levels between the men with ED and without ED.

Materials and method: A total of 177 men were included in the study. Ninety-five men with ED and 82 men without ED (control). All men were evaluated for ED by Index of Erectile Function-5 items (IIEF-5). VAI levels were calculated using body mass index, high density lipoprotein and tryglyceride levels.

Results: Mean age was 53.5 (38–69) in men who have ED and 53.1 (34–69) in control. The men with ED had higher body mass index (BMI), triglyceride (TG) levels, higher waist circumference (WC) and lower high-density lipoprotein-cholesterol (HDL-C) levels. Mean VAI level was 5.18?±?2.50 in study group and 3.47?±?1.76 in control goup, respectively. VAI levels were statistically higher in men with ED (p?Discussion: The simplicity of WC and BMI measurement and TG and HDL assessment, make VAI an easily applicable index for the evaluation of visceral fat dysfunction. VAI can be useful index for the evaluation and calculation of erectile dysfunction risk.     

Lower urinary tract symptoms and its potential relation with late-onset hypogonadism

The study of the health status of the aging male takes presently a more integrative approach and it appears that ailments typical of male aging, such as lower urinary tract symptoms (LUTS), (visceral) obesity, metabolic syndrome and erectile failure are significantly interrelated. A common denominator of the above ailments is lower-than-normal testosterone levels occurring in a significant proportion of elderly men. This review addresses the potential connections between LUTS and late-onset hypogonadism. In animal studies there appear to be androgen and estrogen receptors in the urothelium and smooth muscle cells of the urethra and bladder of the rat and rabbit, as well as in the neurons in the autonomic ganglia of the prostatic plexus of the male rat. Upon castration electrically evoked relaxations of the smooth muscle of the prostatic urethra were decreased. There is a Rho-kinase activation/endothelin pathway; possibly involved in the increased smooth muscle activity found in both LUTS/benign prostate hyperplasia. Nitric oxide (NO) appears to have a smooth muscle relaxing effect in the urogenital organs. Studies in humans have convincingly shown that phosphodiestererase inhibitors have a beneficial effect on LUTS. More intervention studies should be undertaken to test the clinical validity of the theoretically plausible interrelationship between LUTS and late-onset hypogonadism.     

Infants' Transitions out of a Fussing/Crying State Are Modifiable and Are Related to Weight Status

Currently, about 10% of infants have a weight for length greater than the 95th percentile for their age and sex, which puts them at risk for obesity as they grow. In a pilot obesity prevention study, primiparous mothers and their newborn infants were randomly assigned to a control group or a Soothe/Sleep intervention. Previously, it has been demonstrated that this intervention contributed to lower weight‐for‐length percentiles at 1 year; the aim of the present study was to examine infant behavior diary data collected during the intervention. Markov modeling was used to characterize infants' patterns of behavioral transitions at ages 3 and 16 weeks. Results showed that heavier mothers were more likely to follow their infants' fussing/crying episodes with a feeding. The intervention increased infants' likelihood of transitioning from a fussing/crying state to an awake/calm state. A shorter latency to feed in response to fussing/crying was associated with a higher subsequent weight status. This study provides preliminary evidence that infants' transitions out of fussing/crying are characterized by inter‐individual differences, are modifiable, and are linked to weight outcomes, suggesting that they may be promising targets for early behavioral obesity interventions, and highlighting the methodology used in this study as an appropriate and innovative tool to assess the impact of such interventions.     

Metabolic impact of shift work

In developing countries, shift work represents a considerable contingent workforce. Recently, studies have shown that overweight and obesity are more prevalent in shift workers than day workers. In addition, shift work has been associated with a higher propensity for the development of many metabolic disorders, such as insulin resistance, diabetes, dislipidemias and metabolic syndrome. Recent data have pointed that decrease of the sleep time, desynchronization of circadian rhythm and alteration of environmental aspects are the main factors related to such problems. Shortened or disturbed sleep is among the most common health-related effects of shift work. The plausible physiological and biological mechanisms are related to the activation of the autonomic nervous system, inflammation, changes in lipid and glucose metabolism, and related changes in the risk for atherosclerosis, metabolic syndrome, and type II diabetes. The present review will discuss the impact of shift work on obesity and metabolic disorders and how disruption of sleep and circadian misalignment may contribute to these metabolic dysfunctions.     

Metabolic Syndrome,Obesity, and Related Risk Factors Among College Men and Women

Abstract

Objectives: The primary objective of this study was to characterize the prevalence of overweight/obesity, metabolic syndrome (MbS) and its criteria, and nutrient intakes of college-age men and women via a large-scale screening. Participants and Methods: From August 2005 to July 2008, 2,722 subjects were recruited for the ongoing, cross-sectional Young Adult Health Risk Screening Initiative project. Anthropometric, biochemical, clinical, and dietary data were collected. Results: Approximately one-half of men and more than one-quarter of women were overweight or obese. MbS was identified in 9.9% of men and 3.0% of women; 77% of men and 54% of women had at least 1 MbS criterion. Intakes of saturated fat, magnesium, and fiber, as well as body mass index and reported physical activity levels were related to MbS. Conclusions: Because of high rates of overweight/obesity and MbS, college-age adults are at risk for developing chronic diseases including diabetes mellitus and cardiovascular disease     

Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) age-related withdrawal is very likely to be involved in the aging process and the onset of age-related diseases, giving rise to the question of whether preventing or compensating the decline of these steroids may have endocrine and clinical benefits. The aim of the present trial was to evaluate the endocrine, neuroendocrine and clinical consequences of a long-term (1 year), low-dose (25?mg/day) replacement therapy in a group of aging men who presented the clinical characteristics of partial androgen deficiency (PADAM). Circulating DHEA, DHEAS, androstenedione, total testosterone and free testosterone, dihydrotestosterone (DHT), progesterone, 17-hydroxyprogesterone, allopregnanolone, estrone, estradiol, sex hormone binding globulin (SHBG), cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were evaluated monthly to assess the endocrine effects of the therapy, while β-endorphin values were used as a marker of the neuroendocrine effects. A Kupperman questionnaire was performed to evaluate the subjective symptoms before and after treatment.

The results showed a great modification of the endocrine profile; with the exception of cortisol levels, which remained unchanged, DHEA, DHEAS, androstenedione, total and free testosterone, DHT, progesterone, 17-hydroxyprogesterone, estrone, estradiol, GH, IGF-1 and β-endorphin levels increased significantly with respect to baseline values, while FSH, LH and SHBG levels showed a significant decrease. The Kupperman score indicated a progressive improvement in mood, fatigue and joint pain.

In conclusion, the present study demonstrates that 25?mg/day of DHEA is able to cause significant changes in the hormonal profile and clinical symptoms and can counteract the age-related decline of endocrine and neuroendocrine functions. Restoring DHEA levels to young adult values seems to benefit the age-related decline in physiological functions but, however promising, placebo-controlled trials are required to confirm these preliminary results.     

Insulin resistance and management of the menopause: a clinical hypothesis in practice

Insulin resistance (IR) is associated with a number of metabolic abnormalities including glucose intolerance, dyslipidemia and central obesity (the metabolic syndrome), which predispose to cardiovascular disease, diabetes mellitus and some cancers. The incidence of many of these conditions increases after the menopause, a time when IR also increases. Medical intervention to help alleviate menopausal symptoms, frequently vasomotor in origin, usually involves hormone replacement therapy (HRT), but some women may only experience partial symptom relief. We have hypothesized that this may be due to concurrent IR. Our approach is therefore to manage menopausal symptoms in conjunction with the treatment of any concurrent IR, achieved through a combination of hormone replacement, dietary intervention and, if necessary, an insulin sensitizer. We suggest that this approach may not only improve symptom relief but may also reduce the risk of developing more serious health complaints in the future.     

Testosterone metabolism,dose–response relationships and receptor polymorphisms: selected pharmacological/toxicological considerations on benefits versus risks of testosterone therapy in men

In this review selected toxicological problems related to testosterone therapy in hypogonadal men are discussed. Applying ‘classical’ pharmacological/toxicological findings (e.g. animal studies on short- and long-term toxicity) to clinical situations is not very helpful. Molecular biological knowledge and especially evaluation of epidemiological studies, as well as intervention studies, on testosterone therapy in hypogonadal men are more useful. Potential risks include overdosage for lifestyle reasons, e.g. excessive muscle building and reduction of visceral obesity, when erythrocytosis occurs concomitantly. Modern galenic formulations of testosterone administration (e.g. transdermal gel, suitable testosterone esters for intramuscular application and newer oral preparations) avoid supraphysiological serum concentrations, therefore significantly reducing the toxicological risk. A hypothetical model of the toxicological risks of testosterone therapy is given that is based on the influence of testosterone metabolism (aromatization vs. reduction) of the respective parameter/target chosen. Finally, the great influence of polymorphisms of the androgen receptor on the assessment of toxicological risk and on the individualization of androgen therapy is shown. Already existing national, continental and international guidelines or recommendations for the testosterone therapy should be harmonized.     

Does Metabolic Syndrome Impair Sexual Functioning in Adults With Overweight and Obesity?

Objectives: Obesity is a growing public health concern worldwide, and results in increased risk of cardiovascular disease, type 2 diabetes, metabolic syndrome, insulin resistance, dyslipidemia, hypertension, and reduced sex hormone production. Previous research suggests that obesity may contribute to sexual dysfunction. This review aims to determine the relationship between obesity and sexual dysfunction, and ascertain the associated cardiometabolic conditions that may contribute to impaired sexual functioning in individuals with obesity. Methods: Literature searches were conducted through PubMed and Embase from 1980 to 2016, to identify original research articles, reviews including systematic reviews and meta-analyses, using the search terms: obese, obesity, overweight, sexual function, sexual dysfunction, metabolic syndrome, CVD, T2D, hormones and weight loss. Results: This review found that individuals with obesity and cardiometabolic comorbidities were more likely to report the greatest degree or sexual dysfunction and/or reduction in sexual quality of life, compared to those without. Conclusions: Current evidence supports an association between sexual dysfunction and factors associated with obesity, such as reduced insulin sensitivity, dyslipidaemia, hypertension, and low oestrogen or testosterone. To establish efficacious treatments, research examining the impact of weight loss on the conditions associated with obesity, such as hypertension, reduced insulin sensitivity, dyslipidaemia, and low sex hormones and sexual functioning in individuals with overweight and obesity should be a priority.     

Physical exercise,nutrition and hormones: three pillars to fight sarcopenia

Background: Sarcopenia is a pathophysiological condition diffused in elderly people; it represents a social issue due to the longer life expectancy and the growing aging population. It affects negatively quality of life and it represents a risk factor for other pathologies, such as diabetes, cardiovascular disease, and obesity. No silver bullet exists to hinder sarcopenia, but it may be counteracted by physical exercise, nutrition, and a proper endocrine milieu. Indeed, we aim to analyze the scientific literature to give to clinician effective advices to counteract sarcopenia.

Main text: Physical exercise, proper nutrition, optimized hormonal homeostasis represent the three pillars to fight sarcopenia. Physical exercise represents the most effective remedy to face sarcopenia, in particular if it is combined with a proper diet and with an adequate endocrine milieu. Consistency in training, adequate daily protein intake and eugonadism seems to be the keys to fight sarcopenia. The combination of these three pillars might act synergistically.

Conclusions: Optimization of these factors may increase their efficiency; however, scientific data may be sometimes confusing so far. Therefore, we aim to give practical advices to clinician to identify and to highlight the most important aspects in each of these three factors that should be addressed.     

The environmental account of obesity: a case for feminist skepticism

There is an emerging consensus among public health advocates that combating obesity is best done by restructuring the environment rather than by stigmatizing individuals. Although feminist scholars have not been major participants in debates over antiobesity policy, recently there has been a move toward adopting the environmental account of obesity as a feminist solution because of its potential to respond to health inequalities along race, class, and gender lines. This article aims to trouble the embrace of the environmental approach by feminist scholars, however, and to resurrect and redirect feminist criticism toward attendant problems of moralism, backlash, and the surveillance and rehabilitation of poor women of color. Despite its overwhelming popularity among policy elites and health researchers, I argue that the environmental account of obesity is not likely to promote structural change and broad redistributions. Rather it makes problematic assumptions about the relationship between health and fat and about the efficacy of intervention strategies, masks moralism with health discourse, and legitimizes punitive, ineffective, and patronizing interventions.     

Overview of the physiological changes and optimal diet in the golden age generation over 50

Basically, our lifespan is determined genetically. However, several other parameters such as the environment, lifestyle and diet have a high impact on living in the best of health. Many older persons suffer from various diseases, which often cannot be avoided; however, their development can be postponed and symptoms can be mitigated by a balanced diet, moderate physical activity as well as a healthy lifestyle. These diseases are, for example, sarcopenia (degenerative loss of muscle mass), osteoporosis (decomposition of bone structure), digestive restrictions, sensory impairment, water imbalance or a compromised immune system. Psychological modifications, obesity and loss of weight also commonly occur in older adults. To define an adequate diet for elderly between the ages 50 and 80 is difficult, even impossible, because the nutritional requirements differ between the dynamic quinquagenarian and the frailer eighty-year-old. However, several studies have shown that sufficient consumption of high-quality proteins, calcium, vitamin D, anti-oxidative food compounds, water as well as adapted energy values and nourishment with high-nutrient density in combination with physical activity especially help one to remain healthy to a great age. The cornerstone of healthy ageing is the maintenance of normal bodyweight in order to prevent the development of diseases such as osteoporosis, coronary heart disease or diabetes type 2. This publication will review the physiological changes that occur with advanced age and consequential nutritional recommendations for elderly persons.     

Hypogonadotrophic hypogonadism in type 2 diabetes

Recent work shows a high prevalence of low testosterone and inappropriately low luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity in patients with type 2 diabetes. However, the duration of diabetes or HbA1c are not related to HH. Furthermore, recent data show that HH is not associated with type 1 diabetes. C-reactive protein concentrations have been shown to be elevated in patients with HH and are inversely related to plasma testosterone concentrations. This inverse relationship between plasma free testosterone and C- reactive protein concentrations in patients with type 2 diabetes suggests that inflammation may play an important role in the pathogenesis of this syndrome. This is of interest since inflammatory mechanisms may have a cardinal role in the pathogenesis of insulin resistance. It is also relevant that in the mouse, deletion of the insulin receptor in neurons leads to HH in addition to a state of systemic insulin resistance. It has also been shown that insulin facilitates the secretion of gonadotrophin releasing hormone (GnRH) from neuronal cell cultures. Thus, HH may be the result of insulin resistance at the level of the GnRH secreting neuron. Low testosterone concentrations are also related to an increase in total and regional adiposity. This review discusses these issues and attempts to make the syndrome relevant as a clinical entity. Clinical trials are required to determine whether testosterone replacement alleviates insulin resistance and inflammation. In addition, low testosterone levels are associated with an increase in cardiovascular events. Testosterone therapy may therefore, reduce cardiovascular risk. This important aspect requires further investigation.