Matthew T. Haren

Frailty and the aging male

Frailty occurs in aging males for a variety of reasons. It is less common in males than females. Diseases which are particularly associated with frailty are diabetes mellitus, atherosclerosis, anemia and chronic obstructive pulmonary disease. Insulin resistance syndrome plays a pathogenetic role in the “fat-frail” syndrome. Sarcopenia occurs predominantly because of hormone deficiency and cytokine excess. Pain and anorexia are also associated with frailty. Stem cell research represents a potential promise for the treatment of frailty.

Frailty and hormones.

“To the three agencies of frugality, fresh air and no worries we would like to add. . . the great importance of the functions of the glands with internal secretion as a means of freeing our body from poisonous products, and thus preventing premature old age. . . on the reinforcement of their functions, if changed by age or disease, by means of extracts obtained from similar organs of healthy animals.”

Testosterone modulates gene expression pathways regulating nutrient accumulation, glucose metabolism and protein turnover in mouse skeletal muscle

Testosterone regulates energy metabolism and skeletal muscle mass in males, but the molecular mechanisms are not fully understood. This study investigated the response of skeletal muscle to castration and testosterone replacement in 8-week-old male mice. Using microarray analyses of mRNA levels in gastrocnemius muscle, 91 genes were found to be negatively regulated by testosterone and 68 genes were positively regulated. The mRNA levels of the insulin signalling suppressor molecule Grb10 and the glycogen synthesis inhibitors, protein phosphatase inhibitor-1 and phosphorylase kinase-γ, were negatively regulated by testosterone. The insulin-sensitive glucose and amino acid transporters, Glut3 and SAT2, the lipodystrophy gene, Lpin1 and protein targeting to glycogen were positively regulated. These changes would be expected to increase nutrient availability and sensing within skeletal muscle, increase metabolic rate and carbohydrate utilization and promote glycogen accumulation. The observed positive regulation of atrogin-1 (Fbxo32) by testosterone could be explained by the phosphorylation of Akt and Foxo3a, as determined by Western blotting. Testosterone prevented the castration-induced increase in interleukin-1α, the decrease in interferon-γ and the atrophy of the levator ani muscle, which were all correlated with testosterone-regulated gene expression. These findings identify specific mechanisms by which testosterone may regulate skeletal muscle glucose and protein metabolism.

Prevalence and factors associated with uncomplicated storage and voiding lower urinary tract symptoms in community-dwelling Australian men

PurposeTo determine the prevalence of, and associated risk factors for, voiding and storage lower urinary tract symptoms (LUTS) in a population-based sample of Australian men.MethodsData were collected from 1,103 men randomly selected, community-dwelling men, as part of the Florey Adelaide Male Ageing Study, after exclusion of men with prostate or bladder cancer or prior surgery to either organ. The presence of LUTS was assessed using the International Prostate Symptom Score. Urine flow was measured via flow meter. Demographic, clinical, and bio-psychosocial data were collected by questionnaire.ResultsThe prevalence of total, storage, and voiding LUTS was 18.1, 28.0 and 12.6%, respectively. The most common storage symptoms were frequency (12.3%), nocturia (9.9%) and urgency (8.1%), and voiding symptoms were weak stream (8.5%), intermittency (5.4%), incomplete emptying (5.1%) and straining (2.4%). There were linear associations between storage LUTS and increased abdominal fat mass, plasma glucose and low HDL cholesterol (components of the metabolic syndrome), obstructive sleep apnoea (OSA) risk, and retirement. Voiding symptoms were associated with a previous diagnosis of benign prostatic enlargement (BPH), mean peak urine flow, total energy intake, elevated risk of OSA, erectile dysfunction, physician-diagnosed thyroid dysfunction and higher household income.ConclusionsThe close association of storage LUTS with the metabolic syndrome, and of both storage and voiding LUTS with OSA, suggest that these conditions should be considered in men presenting with LUTS.

Risk Factors for Progression or Improvement of Lower Urinary Tract Symptoms in a Prospective Cohort of Men

PURPOSE We determined the metabolic, lifestyle and physical factors associated with progression or improvement of storage and voiding lower urinary tract symptoms in a population based cohort of men. MATERIALS AND METHODS After the exclusion of men with prostate or bladder cancer and/or surgery from the study, progression and improvement of storage and voiding lower urinary tract symptoms was assessed using the AUA-SI (American Urological Association symptom index) in 780 men, age 35 to 80 years at baseline, who attended 5-year followup clinics. RESULTS Storage and voiding lower urinary tract symptoms progressed in 39.8% (308) and 32.3% (250) of men, and improved in 33.1% (256) and 23.4% (181), respectively. In final adjusted regression models greater bother and physical activity at baseline predicted improvement in storage and voiding lower urinary tract symptoms, while greater income, high-density lipoprotein cholesterol and lower triglycerides predicted improvement of storage lower urinary tract symptoms only. Being widowed, higher plasma estradiol and depression at baseline predicted the progression of storage and voiding lower urinary tract symptoms, while greater abdominal fat mass and obstructive sleep apnea risk predicted the progression of storage lower urinary tract symptoms only. Older age, lower high-density lipoprotein cholesterol, testosterone, income, previous benign prostatic hyperplasia and erectile dysfunction at baseline predicted the progression of voiding lower urinary tract symptoms only. The initiation or continued use of α-blockers or anticholinergics (storage lower urinary tract symptoms), and 5α-reductase inhibitors (voiding lower urinary tract symptoms), were associated with symptom improvement. CONCLUSIONS Lower urinary tract symptoms may progress or remit. Even accounting for medication use, progression may be associated with modifiable disease, or metabolic or behavioral factors, which are also risk factors for type 2 diabetes and cardiovascular disease. These factors should be looked for and managed.

Defining 'relative' androgen deficiency in aging men: how should testosterone be measured and what are the relationships between androgen levels and physical, sexual and emotional health?

In men, bioavailable and free testosterone levels decline by about 1.0 and 1.2% per year, respectively, after the age of 40. The definition of clinically relevant androgen deficiency in the aging male remains uncertain. Clinical features common to both aging and androgen deficiency include decreased muscle mass and strength, and increased fatigue, increased fat mass, loss of libido, erectile dysfunction, impaired cognitive function and depression. It is, however, difficult to separate the effect on plasma testosterone of concomitant disease, compared with the effects of a decrease in testosterone levels alone. Testosterone supplementation has been shown to be effective in improving many of the clinical features of androgen deficiency in the older male, and is safe, at least in the short term. The maximum benefit occurs in those men with the lowest testosterone levels.

The Florey Adelaide Male Ageing Study (FAMAS): Design, procedures & participants

BackgroundThe Florey Adelaide Male Ageing Study (FAMAS) examines the reproductive, physical and psychological health, and health service utilisation of the ageing male in Australia. We describe the rationale for the study, the methods used participant response rates, representativeness and attrition to date.MethodsFAMAS is a longitudinal study involving approximately 1200 randomly selected men, aged 35–80 years and living in the north – west regions of Adelaide. Respondents were excluded at screening if they were considered incapable of participating because of immobility, language, or an inability to undertake the study procedures. Following a telephone call to randomly selected households, eligible participants were invited to attend a baseline clinic measuring a variety of biomedical and socio-demographic factors. Beginning in 2002, these clinics are scheduled to reoccur every five years. Follow-up questionnaires are completed annually. Participants are also invited to participate in sub-studies with selected collaborators.ResultsOf those eligible to participate, 45.1% ultimately attended a clinic. Non-responders were more likely to live alone, be current smokers, have a higheevalence of self-reported diabetes and stroke, and lower levels of hypercholesterolemia. Comparisons with the Census 2001 data showed that participants matched the population for most key demographics, although younger groups and never married men were under-represented and elderly participants were over-represented. To date, there has been an annual loss to follow-up of just over 1%.ConclusionFAMAS allows a detailed investigation into the effects of bio-psychosocial and behavioural factors on the health and ageing of a largely representative group of Australian men.

Food environment, walkability, and public open spaces are associated with incident development of cardio-metabolic risk factors in a biomedical cohort

We investigated whether residential environment characteristics related to food (unhealthful/healthful food sources ratio), walkability and public open spaces (POS; number, median size, greenness and type) were associated with incidence of four cardio-metabolic risk factors (pre-diabetes/diabetes, hypertension, dyslipidaemia, abdominal obesity) in a biomedical cohort (n=3205). Results revealed that the risk of developing pre-diabetes/diabetes was lower for participants in areas with larger POS and greater walkability. Incident abdominal obesity was positively associated with the unhealthful food environment index. No associations were found with hypertension or dyslipidaemia. Results provide new evidence for specific, prospective associations between the built environment and cardio-metabolic risk factors.

Demographic, physical and lifestyle factors associated with androgen status: the Florey Adelaide Male Ageing Study (FAMAS)

Objective  Plasma androgen levels are inversely associated with health in men, the age‐related decline of which may result from factors other than ageing per se. This study aimed to determine the effects of demographic, physical and lifestyle factors on age‐related androgen status in men.

Clinical and Biopsychosocial Determinants of Sexual Dysfunction in Middle‐Aged and Older Australian Men

INTRODUCTION Erectile dysfunction (ED) and other related sexual dysfunctions in men have recently been shown to associate with a range of conditions and biopsychosocial factors. However, few studies have been able to control for these related factors simultaneously. AIM To determine the prevalence of and associated risk factors for ED and low solitary and dyadic sexual desire. MAIN OUTCOME MEASURES Erectile function (International Index of Erectile Function-erectile function) and sexual desire (Sexual Desire Inventory 2), as well as associated sociodemographic, lifestyle, biological, and clinical risk factors. METHODS Data were collected from 1,195 randomly selected, community-dwelling men as part of the Florey Adelaide Male Ageing Study. RESULTS The prevalence of ED, low solitary, and dyadic sexual desire was 17.7%, 67.7%, and 13.5%, respectively. Increasing age, abdominal fat mass, obstructive sleep apnea risk, and the absence of a regular partner were associated with both degrees of ED severity. Insufficient physical activity, low alcohol consumption, and hypertension were associated with mild ED only, and voiding lower urinary tract symptoms, diabetes, and lower plasma testosterone were independently associated with moderate to severe ED. Increasing age, lower alcohol consumption, insufficient physical activity, and a diagnosis of depression, anxiety, or insomnia were associated with both low dyadic and solitary sexual desire. Postschool qualifications and lower plasma testosterone were associated with low dyadic desire, whereas lower education and income, unemployment, and migration were associated with low solitary sexual desire. The absence of a regular partner and postschool qualifications were associated with higher solitary sexual desire. CONCLUSIONS While ED and low dyadic and solitary sexual desire share some risk factors, we were able to demonstrate that unique factors exist for each of these domains. Attention should first be given to addressing these modifiable risk factors.