Testosterone and obesity in men under the age of 40 years

The study assessed anthropometric and laboratory variables, in particular testosterone (T) in a group of obese men of <40 years. Of 60 men with a body mass index (BMI) of >27 kg m^?2, 34 met the criteria of the metabolic syndrome (MS). Twenty men <40 years (with a BMI <25 kg m^?2) were studied for comparison. It was found that with increasing BMI, levels of serum leptin, triglycerides, insulin, the ratio high‐density lipoprotein (HDL) cholesterol/low‐density liporotein (LDL) cholesterol, the waist circumference (WC), the area of visceral fat and systolic/diastolic blood pressure were higher, whereas insulin sensitivity (HOMA) and serum T were lower. Obesity (BMI 27–30 kg m^?2) was associated with a decline in plasma T, but not with a decline in plasma sex hormone‐binding globulin (SHBG). The latter was the case in more severe obesity (>30 kg m^?2) qualifying as MS. In patients with MS, 58% variability of T levels could be predicted by combination of independent factors – SHBG, ratio LDL/HDL, insulin and leptin. On the other hand, in men with MS, 80% variance of concentrations of SHBG were predicted by triglycerides, HDL, glucose, leptin and surface of visceral adipose tissue. It is concluded that plasma T is significantly correlated with a number of features of the MS and, therefore, plasma T could serve as a marker of the MS.     

Recent topics related to testosterone deficiency syndrome in Japan

Androgens, the levels of which decrease with ageing, play many physiological roles in various organs. Testosterone deficiency syndrome (TDS) has received widespread attention in the last several years. First-line treatment for TDS should be testosterone replacement therapy (TRT), which is reported to improve several TDS symptoms. Recently, a clinical practice manual for TDS was written and published by a collaborative team from the Japanese Urological Association and the Japanese Society for the Study of the Aging Male to recommend standard procedures for the diagnosis, treatment, prevention and monitoring of adverse reactions to TRT and for post-treatment assessment. In this manual, intramuscular injection of testosterone enanthate or human chorionic gonadotropin and the testosterone gel 'Glowmin' were recommended as TRT. Currently, two topics related to TDS are being focused on in Japan: the relationship between TDS and metabolic syndrome and treatment options for eugonadal patients with TDS symptoms. In this review, the possibility of TRT for metabolic syndrome as well as the relationship between testosterone and adiponectin, which is a key molecule in metabolic syndrome, is discussed. Finally, the possibility of herbal medicines as a treatment option for patients with TDS is addressed, especially for eugonadal patients, because eugonadal men with TDS symptoms account for approximately 30% of the general population. The increase in the levels of several cytokines, such as IL-8, IL-13, interferon-γ and tumor necrosis factor-α, after herbal medicine treatment may be the reason for this efficacy.     

Effects of testosterone replacement therapy on metabolic syndrome among Japanese hypogonadal men: A subanalysis of a prospective randomised controlled trial (EARTH study)

We investigated the effects of testosterone replacement therapy (TRT) on metabolic factors among hypogonadal men with a metabolic syndrome. From the study population of the EARTH study, which was a randomised controlled study in Japan, 65 hypogonadal patients with a metabolic syndrome, comprising the TRT group (n = 32) and controls (n = 33), were included in this study analysis. The TRT group was administered 250 mg of testosterone enanthate as an intramuscular injection every 4 weeks for 12 months. Waist circumference, body mass index, body fat volume and blood pressure were measured in all patients at baseline and at 12 months. In addition, blood biochemical data, including total cholesterol, triglyceride (TG), HDL cholesterol, fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) levels, were also evaluated. Changes in these categories from baseline to 12 months were compared between the TRT and control groups, with significant differences observed in waist circumference, body fat percentage, FPG, TG and HbA1c levels. No significant differences were observed in other parameters. TRT for 1 year was associated with improvements in some metabolic factors among Japanese men with hypogonadism and metabolic syndrome.     

Testosterone and Testosterone Binding Globulin (TeBG) in Young Men during Prolonged Stress

The effect of prolonged physical and psychological stress on the testicular function was studied in 8 students (age 22–25 years) of the Norwegian Academy of War during a combat course of 5 days' duration. The average urinary excretion of free cortisol and 17-ketogenic steroids was 81 and 129% higher than the respective control values one week after the course. Plasma cortisol levels increased from 21.7 μg/100 ml at 8 a. m. before the course to 24.6 ( P < 0.05), and serum HGH rose from undetectable levels, < 0.08 ng/ml, to an average value of 12.9 ng/ml ± 3.7 (SD) at 8 a. m. during the course.
A marked suppressive effect on plasma testosterone levels from 5.6 ng/ml ± 1.4 to 0.9 ± 0.5, and no adjustment to stress was observed over a 5 day period. TeBG increased gradually from 26.9 nmol/l ± 9.9 to 52.7 ± 17.7 on day 6, followed by a slow decrease without reaching control values on day 12, suggesting that the decreased plasma testosterone levels probably reflect reduced production and not increased metabolism of testosterone. LH fluctuated during the course, but was significantly higher in the morning immediately following the end of the course than at the start ( P < 0.02). It is postulated that the effect of stress on the plasma testosterone levels is mediated via an action both on the hypothalamus-pituitary level and on the testis.     

Is serum sex hormone-binding globulin a dominant risk factor for metabolic syndrome?

This multi-center, cross-sectional study investigated the association between serum testosterone (T) levels, serum sex hormone-binding globulin (SHBG) levels, and the risk of metabolic syndrome (MS) in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T (TT) and SHBG than those without MS (P < 0.001). There was no significant difference in serum free T (FT) levels between subjects with and without MS (P = 0.627). In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index (BMI), smoking and drinking status, and serum TT (odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954−0.969, P< 0.01). However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status (OR 0.981, 95% CI 0.960−1.007). Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.     

Screening for metabolic syndrome and testosterone deficiency in patients with erectile dysfunction: results from the first UK prospective study

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b

OBJECTIVE

To screen patients with erectile dysfunction (ED) for the presence of metabolic syndrome (MetS), testosterone deficiency and cardiovascular (CV) risk factors, in a secondary referral centre in the UK, as men with ED have a high incidence of CV risk factors that might amount to MetS, with obesity, increased risk of coronary heart disease and type II diabetes; testosterone deficiency has also been associated with both ED and MetS.

PATIENTS AND METHODS

We assessed 124 men presenting with ED between March 2007 and August 2008. Data were collected prospectively for patient demographics, risk factors associated with MetS, and hypogonadism. MetS was assessed using the National Cholesterol Education Program Adult Treatment Panel III Criteria 2005 (based on three or more of five criteria: waist circumference, high triglycerides, low levels of high‐density lipoprotein cholesterol, hypertension and impaired glucose tolerance).

RESULTS

The mean (range) age of the men was 50 (16–76) years; 50 of 124 (40%) patients had MetS and 27% had hypogonadism. The latter was also associated with a low testicular volume and decreased libido. Ninety‐seven patients (82%) were either overweight or obese, and 64 (52%) were current or ex‐smokers.

CONCLUSIONS

Our audit confirms a high incidence of MetS and hypogonadism in patients with ED in the UK. We recommend routine screening for CV risk factors, MetS and testosterone deficiency in all patients in the UK with ED.     

Influence of ageing and some lifestyle factors on male gonadal function: a study in Bulgaria

There are few systematic studies on the relationship between blood testosterone concentrations and the symptoms of androgen deficiency in ageing males. To assess the changes in sex hormone levels with age in relation with some lifestyle factors, the serum levels of total testosterone (TT), sex-hormone binding globulin (SHBG), luteinising hormone (LH) and follicle stimulating hormone (FSH) were measured in 33 men, age range 40-89 years. In addition, free testosterone (FT) and the free androgen index (FAI) were calculated. Seventeen healthy men under 40 years were involved as controls. The men over 40 years revealed significantly decreased TT, FT and FAI, and in the subgroup of men over 60 years, FSH and SHBG were significantly increased. Pearson's analysis showed that TT levels were significantly correlated with body mass index (BMI) (r = -0.464, P < 0.01) and body weight (r = -0.413, P < 0.05). SHBG levels were significantly correlated not only with age (r = +0.407, P < 0.05), but also with LH (r = +0.605, P < 0.001) and alcohol consumption (r = +0.382, P < 0.05). In conclusion, the TT, FT and FAI decreased in males over 40 years, but the alterations in hormone levels with age are more pronounced in men over 60 years. The important determinants of sex hormones are age, BMI and some lifestyle factors.     

Relationship of testosterone, sex hormone binding globulin, and calculated free testosterone to subsequent clinical progress in patients with carcinoma of the prostate treated with bilateral orchidectomy or estrogens

The concentration in serum of testosterone, sex hormone binding globulin (SHBG), and albumin has been measured, and from these measurements free testosterone has been calculated in 75 patients with carcinoma of the prostate treated with either bilateral orchidectomy, stilbestrol, or estramustine phosphate (Estracyt). After exclusion of 3 noncompliant patients, total testosterone did not differ significantly between treatments, but free testosterone was lower in estrogen-treated patients (5.9 +/- 0.9 (SEM) pmol/l, n = 28) compared with the orchidectomized patients (23 +/- 1.4 pmol/l, n = 44) (P less than 0.001); all of the estrogen-treated patients falling in the lower third of the range of the orchidectomized patients. Free testosterone did not change systematically during several years of treatment and there was no evidence of a rise with clinical deterioration. In the 33 patients with metastatic cancer treated with orchidectomy, the third with the lowest free testosterone or total testosterone showed a better survival over 2 years than the two-thirds with higher free or total testosterone; thereafter, the advantage was lost.     

Hypogonadism, ED, metabolic syndrome and obesity: a pathological link supporting cardiovascular diseases

Hypogonadism, erectile dysfunction (ED), visceral adiposity, insulin resistance and metabolic syndrome (MetS) often coexist in the same subjects. This cluster of abnormalities is associated with an increased risk of diabetes and cardiovascular diseases (CVD), affecting not only quality of life but also life expectancy. Longitudinal studies have also demonstrated that ED and male hypogonadism could be considered surrogate markers of incident CVD and MetS. However, how androgens signal fat depots and lessen them is still a matter of active research and whether or not low testosterone could play a pathogenetic role in CVD is still under debate. Hence, pathogenetic mechanisms linking hypogonadism with obesity and insulin resistance appear to be complex and often multi-directional. Visceral obesity can probably be considered a relevant cause of hypogonadism but at the same time, hypogonadism could be a cause of obesity and insulin resistance, consequently establishing a vicious cycle. To provide a critical analysis of these issues, a comprehensive literary search was carried out to discuss the relationship between insulin resistance ED, visceral adiposity, MetS and hypogonadism focusing on their possible involvement in the development of CVD.     

Quantifying cardiovascular risks in patients with metabolic syndrome undergoing total joint arthroplasty

The coexistence of diabetes, hypertension, obesity, and dyslipidemia is defined as metabolic syndrome. Studies show substantial cardiovascular risks among these patients. The risk of patients with metabolic syndrome undergoing total joint arthroplasty (TJA) is unknown. Patients with and without metabolic syndrome undergoing TJA during a 3-year period were analyzed for postoperative complications. Metabolic syndrome was defined by having 3 of the following 4 criteria: obesity (body mass index ≥30 kg/m(2)), dyslipidemia, hypertension, and diabetes. Patients with metabolic syndrome had a significantly higher risk of cardiovascular complications compared with controls (P = .017). The risk of an adverse event increased by 29% and 32%, respectively, when there were 3 or 4 syndrome components. Patients with metabolic syndrome undergoing TJA have increased risk for cardiovascular complications. Our results show that metabolic syndrome may have a clustering effect and pose increased risk when individual risks factors are combined.     

Insulin resistance and sex hormone‐binding globulin are independently correlated with low free testosterone levels in obese males

Male obesity is associated with decreased testosterone levels but the pathophysiological mechanisms behind this association are not completely understood. This study aimed to investigate the impact of hyperglycaemia/insulin resistance and sex hormone‐binding globulin (SHBG) levels on testosterone levels in a population of obese men. We investigated the impact of several clinical, anthropometric and analytic measures on testosterone levels in 150 obese males. Testosterone deficiency was present in 52.0% of the enrolled patients. This percentage dropped to 17.6% when only calculated free testosterone (FT) was accounted, as SHBG levels were correlated negatively with body mass index (r = ?.20; p < .05). Older age (p < .05) and higher homoeostasis model assessment of insulin resistance (HOMA‐IR) (p < .01) and lower SHBG levels (p < .05) were independently correlated with lower FT. Weight and fasting plasma glucose lost their statistical significance after multivariate adjustment. Patients with type 2 diabetes mellitus and pre‐diabetes had lower FT than those with normal glucose tolerance (p < .05 and p < .01 respectively). Insulin resistance, and not hyperglycaemia and weight per se, seems to be the main determinant of low testosterone levels in obese males. Low SHBG levels are correlated with low FT even after HOMA‐IR adjustment. This suggests that SHBG can be associated with testosterone deficiency beyond the influence of insulin resistance unlike previously reported.     

Early development of metabolic syndrome in patients subjected to lung transplantation

Cardiovascular disease is a common cause of morbidity and mortality after solid organ transplantation, due to a combination of pre‐existing cardiovascular risk factors and immunosuppressive drug toxicity. The prevalence of new‐onset hypertension, dyslipidemia, diabetes mellitus, and metabolic syndrome was assessed after lung transplantation in a cohort of 67 patients (mean age: 48 ± 14 yr). The prevalence of hypertension increased from 19.4% to 70.1% at the three‐yr follow‐up visit (p < 0.01). The concomitant prevalence of diabetes and dyslipidemia raised from 13.4% to 31.3%, and from 6.0% to 40.3%, respectively (p < 0.01 for both), and body mass index increased from 22.4 ± 3.7 to 26.1 ± 3.9 kg/m² (p < 0.01). The prevalence of metabolic syndrome increased from 3.0% to 23.9% after the first year, to remain stable thereafter, associated with a strict control of cardiovascular risk factors. A large number of lung transplant recipients develop new‐onset hypertension, diabetes, dyslipidemia after transplantation, and in more than one‐fifth metabolic syndrome can be diagnosed after the first year. The increased cardiovascular risk of these patients should be taken into account during follow‐up, to better define a proper and timely cardiovascular prevention. Adequate control of cardiovascular risk factors, preventing further metabolic syndrome development, is recommended and feasible in lung transplant recipients.     

Serum globulin assay of estrogen-binding ability during endocrine treatment of postmenopausal advanced breast cancer

Estrogen-binding ability of sex hormone binding globulin (SHBG) was assayed in sera of 18 postmenopausal patients with advanced breast cancer during the treatment of diethylstilbestrol by agar gel electrophoresis at low temperature. In eight cases showing high level of SHBG, seven cases (88 per cent) responded to the estrogen therapy. On the contrary, only one case (13 per cent) responded out of eight patients with low level of SHBG. This results may indicate that the level of estrogen binding ability of SHBG (SEBA) is an useful tool in predicting response to estrogen therapy for breast cancer.     

Testosterone therapy has positive effects on anthropometric measures,metabolic syndrome components (obesity,lipid profile,Diabetes Mellitus control), blood indices,liver enzymes,and prostate health indicators in elderly hypogonadal men

To alleviate late‐onset hypogonadism, testosterone treatment is offered to suitable patients. Although testosterone treatment is commonly given to late‐onset hypogonadism patients, there remains uncertainty about the metabolic effects during follow‐ups. We assessed the associations between testosterone treatment and wide range of characteristics that included hormonal, anthropometric, biochemical features. Patients received intramuscular 1,000 mg testosterone undecanoate for 1 year. Patient anthropometric measurements were undertaken at baseline and at each visit, and blood samples were drawn at each visit, prior to the next testosterone undecanoate. Eighty‐eight patients (51.1 ± 13.0 years) completed the follow‐up period. Testosterone treatment was associated with significant increase in serum testosterone levels and significant stepladder decrease in body mass index, total cholesterol, triglycerides and glycated haemoglobin from baseline values among all patients. There was no significant increase in liver enzymes. There was an increase in haemoglobin and haematocrit, as well as in prostate‐specific antigen and prostate volume, but no prostate biopsy intervention was needed for study patients during 1‐year testosterone treatment follow‐up. Testosterone treatment with long‐acting testosterone undecanoate improved the constituents of metabolic syndrome and improved glycated haemoglobin in a stepladder fashion, with no adverse effects.     

Low testosterone levels and unimpaired melatonin secretion in young males with metabolic syndrome

The interrelations between testosterone, insulin and melatonin levels in males with metabolic syndrome (MS) are still not clarified, especially in young age groups. The aim of the present study was to compare the testosterone serum levels in young men with MS to those in healthy controls, and to determine the possible changes in their melatonin rhythm, as well as the relation between melatonin, insulin and lipid profile. Fasting insulin and testosterone concentrations were measured in 10 healthy nonobese and 10 MS patients. Blood samples for melatonin, insulin and luteinizing hormone (LH) were collected at 19.00, 03.00 and 11.00 hours. A significant difference was found between the testosterone levels in controls and patients. Luteinizing hormone levels in both groups were similar, however, higher night LH levels in MS patients were observed. No changes in the melatonin concentrations of the two groups were found. In conclusion, total testosterone levels were significantly lower in young men with MS compared with healthy age-matched controls. Mild hypoandrogenia in hyperinsulinaemic patients was not related with changes in their melatonin levels. No alterations in the endogenous melatonin rhythm of the MS patients were found.     

血清睾酮水平和代谢综合征的关联分析

目的:探讨男性血清睾酮水平和代谢综合征(MS)的关联。方法:2008年11月至2009年2月对北京社区1006例30～60岁男性进行调查,分别检测腰围、血压、空腹血糖、甘油三酯、高密度脂蛋白胆固醇(HDL-C)、血清睾酮等。采用《2007中国成人血脂异常防治指南》推荐的MS诊断标准,分为MS组和非代谢综合征(NMS)两组,比较两组间各项指标水平差异,分析引起MS不同危险因素中血清睾酮水平以及血清睾酮和MS的相关性。结果:两组之间年龄无统计学差异(P>0.05),腰围、收缩压、舒张压、空腹血糖、甘油三酯、HDL-C、血清睾酮比较有显著性差异(P<0.001)。MS成分增多,血清睾酮水平则明显降低(P<0.01)。血清睾酮水平和年龄、腰围、收缩压、甘油三酯呈负相关(P<0.05)。结论:低血清睾酮水平在一定程度上能预示MS的发展。     

Hypogonadism and metabolic syndrome: implications for testosterone therapy

PURPOSE: Metabolic syndrome, characterized by central obesity, insulin resistance, dyslipidemia and hypertension, is highly prevalent in the United States. When left untreated, it significantly increases the risk of diabetes mellitus and cardiovascular disease. It has been suggested that hypogonadism may be an additional component of metabolic syndrome. This has potential implications for the treatment of metabolic syndrome with testosterone. We reviewed the available literature on metabolic syndrome and hypogonadism with a particular focus on testosterone therapy. MATERIALS AND METHODS: A comprehensive MEDLINE review of the world literature from 1988 to 2004 on hypogonadism, testosterone and metabolic syndrome was performed. RESULTS: Observational data suggest that metabolic syndrome is strongly associated with hypogonadism in men. Multiple interventional studies have shown that exogenous testosterone has a favorable impact on body mass, insulin secretion and sensitivity, lipid profile and blood pressure, which are the parameters most often disturbed in metabolic syndrome. CONCLUSIONS: Hypogonadism is likely a fundamental component of metabolic syndrome. Testosterone therapy may not only treat hypogonadism, but may also have tremendous potential to slow or halt the progression from metabolic syndrome to overt diabetes or cardiovascular disease via beneficial effects on insulin regulation, lipid profile and blood pressure. Furthermore, the use of testosterone to treat metabolic syndrome may also lead to the prevention of urological complications commonly associated with these chronic disease states, such as neurogenic bladder and erectile dysfunction. Physicians must be mindful to evaluate hypogonadism in all men diagnosed with metabolic syndrome as well as metabolic syndrome in all men diagnosed with hypogonadism. Future research in the form of randomized clinical trials should focus on further defining the role of testosterone for metabolic syndrome.