Search

The aim of this study was to determine whether testicular volume is correlated with clinical and biochemical markers of hypothalamic-pituitary-testicular (HPT) axis function. This was a cross-sectional substudy of a larger randomized controlled trial including obese men, body mass index (BMI) ≥30 kg m -2 , with a total testosterone level <12 nmol l -1 . Testicular volume was measured by orchidometer, testosterone by liquid chromatography/tandem mass spectrometry, and body composition by dual-energy X-ray absorptiometry. Men completed the Aging Males' Symptoms (AMS) score, International Index of Erectile Function-5 (IIEF-5), physical function, and handgrip dynamometer testing. Eighty-nine men participated with a median (interquartile range [IQR]) age of 53.1 (47.6, 59.2) years, BMI of 37.0 (34.6, 40.5) kg m -2 , and a total testosterone of 7.0 (6.1, 7.9) nmol l -1 . Median testicular volume was 18 (IQR: 10, 20) ml. Testicular volume was negatively correlated with BMI (τ = -0.1952, P = 0.010) and total fat mass (τ = -0.2115, P = 0.005) independent of age and testosterone. When BMI, testosterone, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were present in a multivariable model, only BMI (-0.38 ml change in testicular volume per 1 kg m -2 BMI; 95% CI: -0.74, -0.02; P = 0.04) and LH (-0.92 ml change in testicular volume per 1 IU l -1 LH; 95% CI: -1.75, -0.095; P = 0.03) remained independent significant predictors of testicular volume. Testicular volume was positively correlated with IIEF-5 (τ = 0.2092, P = 0.021), but not related to handgrip strength, physical function tests, or AMS. In obese men, testicular volume is inversely and independently associated with measures of adiposity, but not with most clinical or biochemical markers of HPT axis action. From a clinical perspective, this suggests that obesity might compromise the reliability of reduced testicular volume as a sign of androgen deficiency in men., Competing Interests: None

Background: Male hypogonadism, caused by intrinsic pathology of the hypothalamic-pituitary-testicular (HPT) axis, is an under-diagnosed condition not to be missed. By contrast, late onset hypogonadism (LOH), due to functional suppression of the HPT axis from age-related comorbidities, may be less common than previously believed., Objective: This article outlines the aetiology, clinical features, investigation and management of male hypogonadism and discusses the more controversial area of LOH., Discussion: Pathologically based hypogonadism is, after a thorough diagnostic work-up, treated with testosterone replacement therapy, unless fertility is desired. LOH with modest reductions in testosterone levels should primarily be managed by attention to lifestyle measures, especially weight loss, and optimisation of comorbidities. Clear treatment goals should be identified, and efficacy and safety should be monitored according to published clinical practice guidelines.

With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT) axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen defi ciency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials.

Aim: We aimed to compare the precipitants of acute decompensated heart failure (ADHF) among patients admitted with diagnoses inclusive of ADHF (community patients) and patients admitted without ADHF but who developed it during their stay (hospital patients)., Methods: This was a prospective, analytical, observational study undertaken in the Austin Hospital, a major metropolitan teaching hospital (September 2008-February 2010). Consecutive patients admitted to a general medicine unit, and diagnosed and treated for ADHF were enrolled. The unit medical staff completed a specifically designed data collection document., Results: Three hundred and fifty-nine patients were enrolled (42.9% male, mean age 81.9 years). The community (n=312) and hospital (n=47) patient groups did not differ in age, gender, risk variables (living alone, cognitive impairment, multiple medications, compliance), cardiac failure medication use or cause of known heart failure (ischaemia, hypertension, valve dysfunction, 'other') (p>0.05). The ADHF precipitants comprised infection (39.8% patients), myocardial ischaemia (17.3%), tachyarrhythmia (16.2%), non-compliance with fluid and salt restriction (9.2%), non-compliance with medication (6.7%), renal failure (5.8%), medication reduction (5.0%), intravenous fluid complication (3.9%) and 'other' causes (13.9%). Significantly more hospital patients had their ADHF precipitated by intravenous fluid complications (25.5% versus 0.6%, p<0.001). Hospital patients also had a significantly greater death rate (25.5% versus 9.3%, p<0.01)., Conclusion: Acute decompensated heart failure precipitated in hospital is a dangerous condition with a high mortality. While infection and myocardial ischaemia are the common precipitants, complications of intravenous fluid use, an iatrogenic condition, may be considerable and are potentially avoidable., (Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Kennedy's disease (KD) or spinobulbar muscular atrophy is a hereditary X-linked, progressive neurodegenerative condition caused by an expansion of the CAG triplet repeat in the first exon of the androgen receptor gene. The phenotype in its full form is only expressed in males and presents as weakness and wasting of the upper and lower limbs and bulbar muscles associated with absent reflexes. Sensory disturbances are present. Various endocrine abnormalities including decreased fertility and gynecomastia are common and amongst the first features of KD. Animal models of KD have demonstrated improvement on withdrawal of testosterone, indicating that this agonist of the androgen receptor is required for the toxic effect. Potential therapies based on testosterone withdrawal in humans have shown some promise, but efficacy remains to be proven. Potential clinical factors, pathogenesis and future approaches to therapy are reviewed in this chapter.

Objective: NADPH oxidases are important sources of reactive oxygen species (ROS) in the vasculature. In phagocytic cells, the catalytic subunit of NADPH oxidase is a glycoprotein, gp91phox. However, vascular smooth muscle cells (VSMCs), which show prominent NADPH oxidase activity, lack gp91phox. Hence, we examined the role of Nox4, a gp91phox homologue, in superoxide production in mouse-cultured VSMCs., Methods and Results: Incubation of VSMCs with NADPH increased ROS production whether detected by lucigenin-enhanced chemiluminescence or dichlorofluorescein. Superoxide production was inhibited by the NADPH oxidase inhibitors, diphenyleneiodonium and apocynin, but not by inhibitors of other potential sources of superoxide. In unstimulated VSMCs, phosphorothioate antisense oligonucleotides against Nox4 down-regulated mRNA expression of the subunit by 65% and attenuated superoxide production by 41% without affecting Nox1 expression. Interleukin-1beta (IL-beta) thrombin and platelet-derived growth factor (PDGF) also reduced Nox4 mRNA expression after 3 h without affecting Nox1 levels. Of these stimuli, only IL-beta reduced superoxide, but this effect was more rapid (< or =30 min) than its actions on Nox4., Conclusions: Under resting conditions, NADPH oxidase activity in VSMCs is largely dependent upon Nox4 expression. Proinflammatory mediators down-regulated Nox4 but did not affect Nox1 expression, so other factors must compensate to regulate superoxide production.