Search

Refereed/Peer-reviewed Background: Isolation and social distancing restrictions due to COVID-19 have the potential to impact access to healthcare services. Aims: To assess the use of pathology services during the COVID-19 pandemic initial restrictions. Methods: Repeated cross-sectional study of pathology tests utilisation during a baseline time period early in 2020 compared with pre-lockdown and lockdown due to COVID-19 in South Australia. The outcome measure was changed in a number of pathology tests compared to baseline period, particularly change in the number of troponin tests to determine potential impacts of lockdown on urgent care presentations. Results: In the community setting, the ratio of a number of pathology tests pre-lockdown and post-lockdown versus baseline period decreased from 1.02 to 0.53 respectively. The exception was microbiology molecular tests, where the number of tests was more than three times higher in the lockdown period. The number of troponin tests in emergency departments decreased in the lockdown period compared to the baseline time period; however, there was no evidence of an association between tests result (positive vs negative) and time period (odds ratio (OR) 1.09; 95% confidence interval (CI) 0.97–1.22). There was an inverse relationship between age and time period (OR 0.995; 95% CI 0.993–0.997), indicating that fewer troponin tests were conducted in older people during the lockdown compared with the baseline period. Conclusion: COVID-19 restrictions had a significant impact on the use of pathology testing in both urgent and non-urgent care settings. Further studies are needed to investigate the effect on health outcomes as a result of the COVID-19 restrictions.

Background: Multimorbidity has been identified as a serious challenge on global health system, closely associated with lower quality of life, poorer health outcomes, and higher utilisation of health services. However, there are major gaps in our knowledge around multimorbidity, especially its effect on primary care services and the burden of comorbid mental health conditions on multimorbidity patterns. This study sought to determine patterns of multimorbidity and quantify their impact on use of primary health services in the presence and absence of anxiety and depression among a cohort of urban community-dwelling men. Methods: This was a prospective cohort study with Australian population. The study population consisted of 2,039 men aged ≥40, who were enrolled either in the Florey Adelaide Male Ageing Study (FAMAS) Stage 2 between 2007-2010 or in the North-West Adelaide Health Study (NWAHS) Stage 3 between 2008-2010. Data have been collected on the prevalence of 8 chronic conditions and linked Medicare data about individual health service utilization information on annual GP visits. Multinomial logistic regression was adopted to quantify the impact of anxiety and depression on the frequencies of GP visits, with adjustment for participant’s demographic and lifestyle characteristics. Results: Obesity and cardiovascular disease (CVD) were associated with the highest number of comorbid conditions. Two non-random multimorbidity “clusters” emerged: (CVD, Obesity, Diabetes) and (CVD, Obesity, Osteoarthritis). Participants with conditions comorbid with CVD were more likely to have 10 or more annual GP visits, compared to multimorbidity involving other conditions. Comparing to participants without CVD, the presence of CVD increased the chance of having 10 or more annual GP visits (adjusted risk ratio: 3.7; 95% CI: 2.8-4.8). When CVD was comorbid with anxiety and depression having 10 or more annual GP visits was more common (adjusted risk ratio: 1.8; 95% CI: 1.2-2.5). Conclusions: In Australian, community-dwelling men, multimorbidity is associated with a high use of GP services; especially for multimorbidity that includes CVD with comorbid anxiety and depression. Multimorbidity patterns involving CVD should be considered in developing clinical trials to better inform medical decision making and care for patients with CVD and comorbid conditions.

ContextSex hormone–binding globulin (SHBG) levels are associated with cardiovascular disease (CVD) risk factors. However, prospective data on the association between SHBG levels and CVD events are sparse, with conflicting results.ObjectivesTo examine associations between serum SHBG, total testosterone (TT), and incident CVD and CVD-related mortality in middle-aged to elderly men.Design and MethodsData on 2563 community-dwelling men (35 to 80 years) were obtained from participants in the Men Androgen Inflammation Lifestyle Environment and Stress cohort. The analytic sample included 1492 men without baseline (2002 to 2007) CVD and with fasted morning serum SHBG and TT available at both baseline and follow-up (2007 to 2010) and without medications affecting TT or SHBG. Associations of baseline SHBG and TT, with incident CVD and CVD mortality, were analyzed using logistic regression for incident CVD and Cox proportional hazard regression for CVD mortality, adjusting for established CVD risk factors.ResultsIn multivariable models, elevated baseline SHBG and lower baseline TT were independently associated with incident CVD (SHBG: OR, 1.54; 95% CI, 1.15 to 2.06 per SD increase in SHBG, P = 0.003; TT: OR, 0.71; 95% CI, 0.52 to 0.97 per SD decrease in TT; P = 0.03). A decrease in TT between time points was associated with incident CVD (OR, 0.72; 95% CI, 0.56 to 0.92; P = 0.01). Neither SHBG nor TT was significantly associated with all-age CVD mortality [hazard ratio (HR), 0.69; 95% CI, 0.29 to 1.63; P = 0.40; and HR, 0.60; 95% CI, 0.28 to 1.26; P = 0.18, respectively].ConclusionsAmong all men and men >65 years, elevated SHBG and lower TT were independently associated with both a greater risk of CVD and an increased CVD mortality risk.

Objective: Contrasting findings exist regarding the associations between circulating sex hormone-binding globulin (SHBG) and total testosterone (TT) with type 2 diabetes (T2D) and cardiovascular diseases (CVD) in men. We examined prospective associations of SHBG and TT with incident T2D and CVD, in a cohort of community-dwelling men. Methods: Participants were aged 35 years and over at enrolment (n=2563) and followed for an average of 4.95 years. This analysis included men without T2D (1597) or CVD (1492) at baseline, and with fasted morning serum SHBG (chemiluminescent immunoassay) and TT (LCMSMS) at both time points, and without meds affecting TT or SHBG. T2D was identified by either self-report, fasting glucose (≥7.0 mmol/L), HbA1c (≥ 6.5%) and/or prescriptions for diabetes medications. CVD was ascertained by self-report and/or hospital data linkage. Logistic binomial regressions were used to assess associations between SHBG and incident T2D & CVD, adjusting for self-reported psycho-social, demographic and health status and related behavioural factors; measured waist circumference, HBA1c and plasma glucose, triglycerides, high-sensitivity C-reactive protein. Sensitivity analyses assessed mediation effects of anxiety, sleep duration, shift work ≥3years, and obstructive sleep apnoea (OSA). Results: During an average follow-up of 4.95 years, 14.5% (n=232) and 6.7% (n=101) of men developed T2D and CVD, respectively. Baseline TT was independently associated with incident T2D (odds ratio (OR) =0.72, 95%CI= [0.57, 0.92], P=0.01). An inverse association of baseline SHBG levels with incident T2D (OR=0.77 [0.62, 0.95], P=0.02), was insignificant after adjustment for TT (OR=0.91 [0.71, 1.17], P=0.48 for SHBG. Baseline TT (OR=0.71 [0.52, 0.98], P=0.04) and SHBG (OR=1.54 [1.15, 2.06], P=0.003) were independently associated with incident CVD. A decrease in TT between time points was associated with incident T2D (OR=0.81 [0.68, 0.97], P=0.02) and CVD (OR=0.72 [0.56,0.92], P=0.01). There was no association between ΔSHBG and incident T2D and CVD. In the sensitivity analyses there was evidence for mediation effects of shift-work on the association of TT, but not SHBG with CVD (both baseline &change models), and of longer sleep duration, OSA and shift work on the association of TT with T2D (change TT model only). Conclusions Shift-work mediates associations of TT with CVD. All sleep parameters had mediation effects on the association of decreasing TT with T2D. Funding: NH&MRC Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Contrasting findings exist regarding the association between circulating sex hormone-binding globulin (SHBG) and testosterone levels and type 2 diabetes (T2D) in men. We examined prospective associations of SHBG and sex steroids with incident T2D in a cohort of community-dwelling men. Participants were from a cohort study of community-dwelling (n = 2563), middle-aged to elderly men (35–80 years) from Adelaide, Australia (the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study). The current study included men who were followed for 5 years and with complete SHBG and sex steroid levels (total testosterone (TT), dihydrotestosterone (DHT) and oestradiol (E2)), but without T2D at baseline (n = 1597). T2D was identified by either self-report, fasting glucose (≥ 7.0 mmol/L), HbA1c (≥ 6.5%/48.0 mmol/mol), and/or prescriptions for diabetes medications. Logistic binomial regression was used to assess associations between SHBG, sex steroids and incident T2D, adjusting for confounders including age, smoking status, physical activity, adiposity, glucose, triglycerides, symptomatic depression, SHBG and sex steroid levels. During an average follow-up of 4.95 years, 14.5% (n = 232) of men developed new T2D. Multi-adjusted models revealed an inverse association between baseline SHBG, TT, and DHT levels, and incident T2D (odds ratio (OR) = 0.77, 95% CI [0.62, 0.95], p = 0.02; OR 0.70 [0.57, 0.85], p

Despite its widespread clinical use, there is little data available from population-based studies on the determinants of serum sex hormone binding globulin (SHBG). We aimed to examine multifactorial determinants of circulating SHBG levels in community-dwelling men. Study participants comprised randomly selected 35–80 y.o. men (n = 2563) prospectively-followed for 5 years (n = 2038) in the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study. After excluding men with illness or medications known to affect SHBG (n = 172), data from 1786 men were available at baseline, and 1476 at follow-up. The relationship between baseline body composition (DXA), serum glucose, insulin, triglycerides, thyroxine (fT4), sex steroids (total testosterone (TT), oestradiol (E2)), and pro-inflammatory cytokines and serum SHBG level at both baseline & follow-up was determined by linear and penalized logistic regression models adjusting for age, lifestyle & demographic, body composition, metabolic, and hormonal factors. Restricted cubic spline analyses was also conducted to capture possible non-linear relationships. At baseline there were positive cross-sectional associations between age (β = 0.409, p

Introduction The progress and determinants of sexual dysfunction in middle‐aged and elderly men remain unclear. Aim To describe the incidence or remission and biopsychosocial predictors of erectile dysfunction (ED) and low sexual desire (SD). Main Outcome Measures Erectile function (International Index of Erectile Function) and sexual desire (Sexual Desire Inventory 2) were assessed at follow‐up. Sociodemographic, lifestyle, and health‐related factors were examined in multivariate models of ED and low SD. Methods Data were collected from 810 randomly selected men residing in northern and western Adelaide, Australia, and aged 35–80 years at baseline, who made clinic visits 5 years apart. Results At baseline, 23.2% (n = 123) of men had ED. ED incidence and remission were observed in 31.7% (n = 179) and 29.0% (n = 71) of eligible men, respectively. At baseline, 19.2% (n = 165) had low solitary sexual desire, and 6.0% (n = 50) had low dyadic sexual desire; incidence of low sexual desire occurred in 17.6% (n = 83) (solitary) and 8.3% (n = 51) (dyadic), while remission occurred in 15.4% (n = 68) (solitary) and 22.6% (n = 40) (dyadic) of men. In the final regression models, predictors of incident ED were higher age, lower income, higher abdominal fat mass, low alcohol intake, higher risk of obstructive sleep apnea (OSA) risk, voiding lower urinary tract symptoms (LUTS), depression, and diabetes. Predictors of ED remission were lower age, current employment, and absence of voiding LUTS, angina, diabetes, and dyslipidemia. Predictors of low dyadic SD incidence included higher age, never having been married, widowhood, being unemployed, being retired, insufficient physical activity, and low alcohol intake. Predictors of low dyadic SD remission were being married, not being widowed, higher income, lower abdominal fat mass, lower OSA risk, and higher plasma testosterone. Predictors of low solitary SD included never having been married, being unemployed, low alcohol intake, lower testosterone, storage LUTS, and hypertension. Predictors of low solitary SD remission were being married, being employed, higher income, higher physical activity, moderate alcohol intake, and depression. Conclusions Sexual dysfunction in aging men is a dynamic disorder whose incidence and remission are predicted by a range of modifiable risk factors. Martin SA, Atlantis E, Lange K, Taylor AW, O'Loughlin P, Wittert GA, and members of the Florey Adelaide Male Ageing Study (FAMAS). Predictors of sexual dysfunction incidence and remission in men. J Sex Med 2014;11:1136–1147.

Background Effective prevention of type 2 diabetes (T2D) requires early identification of high-risk individuals who might benefit from intervention. We sought to determine whether low serum testosterone, a novel risk factor for T2D in men, adds clinically meaningful information beyond current T2D risk models. Methods The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study population consists of 2563 community-dwelling men aged 35–80 years in Adelaide, Australia. Of the MAILES participants, 2038 (80.0 %) provided information at baseline (2002–2006) and follow-up (2007–2010). After excluding participants with diabetes (n = 317), underweight (n = 5), and unknown BMI status (n = 11) at baseline; and unknown diabetes status (n = 50) at follow-up; 1655 participants were followed for 5 years. T2D at baseline and follow-up was defined by self-reported diabetes, or fasting plasma glucose (FPG) ≥7.0 mmol/L (126.1 mg/dL), or glycated haemoglobin (HbA1c) ≥6.5 %, or diabetes medications. Risk models were tested using logistic regression models. Sensitivity, specificity, positive predictive values (PPV) were used to identify the optimal cut-off point for low serum testosterone for incident T2D and the area under the receiver operating characteristic (AROC) curve was used to summarise the predictive power of the model. 15.5 % of men had at least one missing predictor variable; addressed through multiple imputation. Results The incidence rate of T2D was 8.9 % (147/1655) over a median follow-up of 4.95 years (interquartile range: 4.35-5.00). Serum testosterone level predicted incident T2D (relative risk 0.96 [95 % CI: 0.92,1.00], P = 0.032) independent of current risk models including the AUSDRISK, but did not improve corresponding AROC statistics. A cut-off point of

Purpose: To define specific medical conditions associated with clinically significant depressive symptoms in men. Methods: A cross-sectional study was conducted in a community-based sample of Australian men (N = 1,195, aged 35–80 years; for 2002–2005). Depression was defined by: (1) symptomatic depression (current symptoms) or (2) current prescription for antidepressant(s) or (3) previously diagnosed depression. Logistic regression was used to determine prevalence odds ratios (OR) for depression independently associated with an extensive range of demographic, lifestyle, and clinical factors. Adjusted population attributable risk (PAR%) estimates were also computed. Results: Depression was significantly (ORs at P < 0.05) associated with previously diagnosed anxiety (12.0) and insomnia (4.4), not married (1.7), current smoker (1.7), low muscle strength tertile (1.7, P = 0.059), high triglycerides (1.6), high storage lower urinary tract symptoms (LUTS) tertile (1.8), past year general practitioner visits 5–9 (1.9), middle energy density tertile (0.4), and high systolic blood pressure (0.5). Significant PAR% estimates (at P < 0.05) were for previous anxiety (27.0%) and insomnia (16.1%), middle energy density tertile (−17.2%), high SBP (−23.5%), high triglycerides (15.2%), and high storage LUTS tertile (12.6%). Results strengthened when depression-related factors (previous anxiety and insomnia, psycholeptics, and cognition) were omitted, and became significant for CVD (OR 1.6; PAR 13.9%). Conclusions: Medical conditions associated with depression in men include high triglycerides, low muscle strength, CVD, and LUTS. Depressed men are likely to use health services frequently, be current smokers, not be married, eat unhealthily, and report previous diagnosis of anxiety and insomnia; which has important implications for clinicians managing male patients. Refereed/Peer-reviewed

The association between increased risk of hip fracture and low vitamin D status has long been recognized. However, the level of vitamin D required to maintain bone strength is controversial. We used a rodent model of vitamin D depletion to quantify the 25-hydroxyvitamin D (25D) levels required for normal mineralization. Six groups of 10-wk-old male Sprague-Dawley rats (n = 42) were fed a diet containing 0.4% calcium and various levels of dietary vitamin D(3) for 4 mo to achieve stable mean serum 25D levels ranging between 10 and 115 nM. At 7 mo of age, animals were killed, and the histomorphometry of distal and proximal femora and L(2) vertebra was analyzed. Total RNA was extracted from whole femora for real-time RT-PCR analyses. In the distal femoral metaphysis, trabecular bone mineral volume (BV/TV) showed a significant positive association with circulating 25D levels (r(2) = 0.42, p < 0.01) in the animals with serum 25D levels between 20 and 115 nM. Osteoclast surface (Oc.S) levels were positively associated with RANKL:OPG mRNA ratio, higher in groups with lower serum 25D levels, and were independent of serum 1,25D levels. Serum 25D levels 80 nM are needed for optimal bone volume. These data indicate that serum 25D levels are a major determinant of osteoclastogenesis and bone mineral volume and are consistent with the levels of 25D recommended to reduce the risk of fracture in humans.

Summary Objective To determine the effects of menopause on bone-related variables in Indonesian women and to compare them with corresponding data in Caucasian Australian women. Design A study of bone-related variables in women aged 45 ‐55 years in Jakarta compared with corresponding historical data from Caucasian Australian women. Measurements Dietary intakes, bone mineral density (BMD) and calcium-related variables in blood and urine. Results Dietary calcium, phosphorus and protein intakes were significantly lower in the women from Jakarta than in those from Adelaide (all P < 0·001), probably because of lower milk consumption, but energy intake was similar in the two cities. Indonesian women were shorter and lighter than Australian women ( P < 0·001) but had a comparable body mass index (BMI). The Indonesians also had a lower spinal BMD than the Australians but this was accounted for by the differences in height and weight between the two populations. The differences in serum and urinary calcium and phosphate and serum alkaline phosphatase across the menopause were comparable in Indonesian and Australian women but creatinine excretion was 25% lower in Jakarta than in Adelaide ( P < 0·001) and this was probably sufficient to account for higher ratios of some urinary solutes to urinary creatinine in the Indonesians. Serum 25-hydroxyvitamin D (25OHD) levels were significantly lower ( P < 0·001) and serum PTH levels significantly higher ( P = 0·0045) in Jakarta than in Adelaide. Conclusions The differences in bone-related biochemical variables across the menopause were similar in the two populations, but calcium and protein intake and urine creatinine were lower in Indonesian than in Australian women. Serum 25OHD was lower and PTH higher in the Indonesian women, probably because of their darker skin, their practice of avoiding direct sunlight and the heavy atmospheric pollution in Jakarta.

To study the role of vitamin D to optimise bone architecture, we have developed an animal model to investigate the effects of frank vitamin D-deficiency as well as graded depletion of circulating 25-hydroxyvitamin D(3) (25D) levels on the skeleton. Rats fed on dietary vitamin D levels from 0 to 500 ng/day achieved diet-dependent circulating levels of 25D ranging from 11 to 115 nmol/L. Levels of serum 1,25-dihydroxyvitamin D(3) (1,25D) increased as dietary vitamin D increased between 0 and 200 ng/day at which point a maximum level was achieved and retained with higher vitamin D intakes. The renal levels of 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1) mRNA were highest in animal groups fed on vitamin D between 0 and 300 ng/day. In contrast, renal 25-hydroxyvitamin D 24-hydroxylase (CYP24) mRNA levels increased as dietary vitamin D increased achieving maximum levels in animals receiving 500 ng vitamin D/day. This animal model of vitamin D depletion is suitable to provide invaluable information on the serum levels of 25D and dietary calcium intake necessary for optimal bone structure. Such information is essential for developing nutritional recommendations to reduce the incidence of osteoporotic hip fractures.

Background The relationship between lower urinary tract symptoms (LUTS) and common mental health disorders such as depression and anxiety in men remains unclear. Inflammation has recently been identified as an independent risk factor for LUTS and depression. This study aimed to assess the association between depression, anxiety and LUTS, and the moderating influence of systemic inflammation, in the presence of other biopsychosocial confounders. Methods Participants were randomly-selected from urban, community-dwelling males aged 35–80 years at recruitment (n = 1195; sample response rate:67.8%). Of these, 730 men who attended baseline (2002–5) and follow-up clinic visits (2007–10), with complete outcome measures, and without prostate or bladder cancer and/or surgery, neurodegenerative conditions, or antipsychotic medications use, were selected for the present study. Unadjusted and multi-adjusted regression models of incident storage and voiding LUTS and incident depression and anxiety were combined with serum inflammatory markers (high-sensitive C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-α), interleukin–6 (IL–6), myeloperoxidase (MPO), soluble e-selectin (e-Sel)) and socio-demographic, lifestyle, and health-related factors. Hierarchical multiple regression was used to assessed the moderating effect of inflammatory markers. Results The incidence of storage, voiding LUTS, depression and anxiety was 16.3% (n = 108), 12.1% (n = 88), 14.5% (n = 108), and 12.2% (n = 107). Regression models demonstrated that men with depression and anxiety at baseline were more likely to have incident storage, but not voiding LUTS (OR: 1.26, 99%CI: 1.01–4.02; and OR:1.74; 99%CI:1.05–2.21, respectively). Men with anxiety and storage LUTS at baseline were more likely to have incident depression (OR: 2.77, 99%CI: 1.65–7.89; and OR:1.45; 99%CI:1.05–2.36, respectively), while men with depression and voiding LUTS were more likely to have anxiety at follow-up (OR: 5.06, 99%CI: 2.81–9.11; and OR:2.40; 99%CI:1.16–4.98, respectively). CRP, TNF-α, and e-Sel were found to have significant moderating effects on the development of storage LUTS (1.06, 0.91–1.96, R2 change: 12.7%), depression (1.17, 1.01–1.54, R2 change: 9.8%), and anxiety (1.35, 1.03–1.76, R2 change: 10.6%), respectively. Conclusions There is a bidirectional relationship between storage, but not voiding, LUTS and both depression and anxiety. We observed variable moderation effects for selected inflammatory markers on the development of depression, anxiety and storage LUTS.

OBJECTIVE: Because it has been reported that vitamin D, given to mother or infant, can prevent type I diabetes in children, that diabetes is more common in adults with low serum vitamin D and that insulin secretion and action are related to vitamin D levels in healthy young adults we examined the relationship between serum vitamin D metabolites and fasting serum glucose in patients attending our outpatient clinics. DESIGN: Retrospective examination of convenience sample of postmenopausal women attending our osteoporosis clinics. PATIENTS: A total of 753 postmenopausal women attending a university hospital outpatient clinic and not on any treatment known to affect glucose metabolism. MEASUREMENTS: Body weight and height, serum 25-hydroxyvitamin D [25(OH)D], serum 1,25-dihydroxyvitamin D [1,25(OH)2D], serum PTH and fasting serum glucose. RESULTS: On simple correlation fasting serum glucose was a positive function of age (P < 0.05), weight (P < 0.001) and body mass index (BMI) (P < 0.001) and a negative function of serum 25(OH)D (P < 0.001), but it was not significantly related to either serum 1,25(OH)2D, PTH or creatinine. When fasting serum glucose was regressed simultaneously on age, BMI and 25(OH)D, glucose was still an inverse function of 25(OH)D (P = 0.006). CONCLUSIONS: Fasting serum glucose increased as 25(OH)D levels fell throughout the range of serum 25(OH)D measured but the greatest increase was observed in those with 25(OH)D below 40 nmol/l.

Intestinal calcium absorption accounts for 60% of the variance in calcium balance and is therefore a potentially very important determinant of bone status. Whether measured by the balance technique or with radiocalcium, it is known to be significantly reduced in postmenopausal women with vertebral and hip fractures. By contrast, there is very little information about calcium absorption in other types of postmenopausal fracture. We now report a series of 549 untreated, Caucasian postmenopausal women in whom we recorded prevalent fractures, measured radiocalcium absorption, and obtained radiographs of the lateral thoracic and lumbar spine. Of these women, 172 had no prevalent fractures, showed normal spine radiographs, and served as controls; 72 had one or more peripheral fractures but normal spine radiographs; 147 had one or more wedged or crushed vertebrae but no peripheral fractures; and 158 had a history of peripheral fracture and one or more fractured vertebrae. Age-adjusted radiocalcium absorption was significantly lower in the two groups with spinal fractures than in the controls ( P

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.

Objective The role of endogenous testosterone in the pathogenesis of type 2 diabetes mellitus remains vague. We investigated whether associations between endogenous testosterone and diabetes prevalence in men could be partially explained by modifiable risk factors. Study design A random population-based cross-sectional study of 1195 men aged 35–80 years living in the north-west regions of Adelaide, Australia. Data collections occurred between 2002 and 2005, and response rate was 45.1%. Materials and methods Diabetes (non-specific) was classified by either: (1) self-report for doctor diagnosis of diabetes; (2) prescription medication for diabetes; (3) fasting plasma glucose ≥7 mmol/L; or (4) glycosylated haemoglobin ≥6.2%. Logistic regressions were used to estimate odds ratios (OR [with 95% confidence intervals]) for diabetes, with stepwise adjustments for demographic, lifestyle, and clinical factors. Results Diabetes prevalence was positively associated with age groups 45–54 years (2.8 [1.4, 5.8]), 55–64 years (3.9 [1.9, 8.3]) and ≥65 years (4.0 [1.8, 8.9]), lowest income group (1.8 [1.0, 3.4]), ex-smoker (1.8 [1.2, 2.9]), lowest (3.2 [1.9, 5.5]) and middle (1.9 [1.1, 3.4]) alcohol tertiles, cardiovascular disease (1.9 [1.2, 2.8]), metabolic syndrome (4.0 [2.6, 6.1]), and lowest plasma total testosterone tertile (1.8 [1.1, 3.0]), but negatively associated with middle (0.5 [0.3, 0.8]) and highest (0.4 [0.3, 0.7]) sugar intake tertiles, arthritis (0.6 [0.3, 1.0]), and elevated LDL cholesterol (0.5 [0.3, 0.8]); ORs showed an inverted ‘U’ shape for middle and highest voiding lower urinary tract symptoms tertiles. Body composition, muscle strength, and cardio-metabolic factors partially explained the association between low plasma total testosterone and diabetes. Conclusions Plasma total testosterone was inversely and independently associated with diabetes prevalence, that might have been partially explained by several modifiable risk factors.

We have previously shown that vitamin D deficiency in young male rats results in significant reduction in femoral trabecular bone volume (BV/TV). However, the effects of vitamin D deficiency and its impact on other relevant skeletal sites remain unclear. Ten week old male Sprague-Dawley rats were fed various levels of vitamin D3 (2, 4, 8, and 12 IU/day) with standard Ca (0.4%) until 30 weeks of age and achieved stable serum 25-hydroxyvitamin D3 (25D) levels between 16 and 117 nmol/L. At time of death, femora, L2 vertebrae and tibiae were processed for bone histomorphometric analyses and tibial cortical strength by 3-point mechanical testing. A significant association between serum 25D and trabecular bone occurred for both the distal femoral metaphysis (R2 = 0.34, P < 0.05) and L2 vertebrae (R2 = 0.24, P < 0.05). Tibia mid-shaft cortical bone was not, however, changed in terms of total volume, periosteal surface or endosteal surface as a function of vitamin D status. Furthermore, no changes to mechanical and intrinsic properties of the cortices were observed. We conclude that cortical bone is maintained under conditions of vitamin D deficiency in preference to cancellous bone in young growing rats. Refereed/Peer-reviewed

We wanted to measure forearm mineral density and bone-related biochemical variables in patients with Klinefelter's syndrome.Measurements made in patients with Klinefelter's syndrome were compared to those obtained in age-matched normal male volunteers.We studied 22 patients with Klinefelter's syndrome (12 of whom had received sex hormone therapy) and 22 control subjects.We measured forearm mineral density, forearm fat content, fat-corrected forearm mineral density, plasma calcium and ionized calcium, serum osteocalcin, testosterone and dehydroepiandrosterone sulphate, and urinary hydroxyproline/creatinine ratio.Forearm mineral density was lower in the Klinefelter's group than in the control subjects (P less than 0.05) and below the control range in 5 patients. The fat content of the forearm was greater in the Klinefelter's group (P less than 0.002). Serum osteocalcin and testosterone were lower, while ionized calcium and the urinary hydroxyproline/creatinine ratio were higher in the Klinefelter's group (P less than 0.002). Serum dehydroepiandrosterone sulphate and testosterone were significantly related in the Klinefelter's group (r = 0.64, P less than 0.001), but not in the controls (r = 0.22, NS). Forearm mineral density and fat-corrected forearm mineral density were significantly related to serum testosterone in the Klinefelter's group (r less than 0.63; P less than 0.01), but not in the control subjects (r less than 0.03, NS).Decreased bone density occurs in about 25% of patients with Klinefelter's syndrome and probably reflects both decreased bone formation and increased bone resorption.

The plasma cell (PC) malignancy, multiple myeloma (MM), is unique among hematological malignancies in its capacity to cause osteoclast (OC)-mediated skeletal destruction. We have previously shown that elevated plasma levels of PC-derived CXCL12 are associated with presence of X-ray detectable osteolytic lesions in MM patients. To further investigate this relationship, plasma levels of CXCL12 and betaCrossLaps, a marker of bone loss, were measured. A strong correlation between levels of CXCL12 and OC-mediated bone resorption was identified. To confirm the OC-activating potential of MM PC-derived CXCL12 in vivo, we established a model of MM-mediated focal osteolysis, wherein MM PC lines, such as RPMI-8226, were injected into the tibias of nude mice. Implanting RPMI-8226 gave rise to osteolytic lesions proximal to the tumor, resulting in a 5% decrease in bone volume (BV) compared with vehicle control. Importantly, bone loss was significantly inhibited with systemic administration of the CXCL12/CXCR4 antagonist T140. Furthermore, implanting CXCL12-overexpressing RPMI-8226 cells resulted in a 13% decrease in BV and was associated with increased OC recruitment proximal to the tumor, increased serum matrix metalloproteinase activity, and increased levels of collagen I degradation products. These findings confirm our hypothesis that MM PC-derived CXCL12 stimulates the recruitment and activity of OC, thereby contributing to the formation of MM osteolytic lesions.

Summary 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. Design An observational survey of a regionally representative male population residing in the North West regions of Adelaide, Australia. Participants Study sample includes 1195 men aged 35–81 years with a response rate of 45·1%. Measurements Plasma levels of total testosterone (TT), bioavailable testosterone (BT), SHBG, insulin-like peptide 3 (INSL3), and gonadotrophins were measured along with an extensive list of demographic, physical and lifestyle factors including body composition, muscle strength and biomarkers of chronic diseases, physical activity, nutrition and smoking behaviour. Results Low TT was mostly associated with high abdominal fat and triglycerides and low muscle strength rather than ageing per se. Low BT was associated with increased age followed by high whole body fat percentage. BT and TT levels were higher in unmarried men and smokers. SHBG levels increased with age, but were also inversely associated with insulin and triglycerides. The Leydig cell specific factor INSL3 was the strongest biomarker associated with both TT and BT. Conclusions Factors associated with low androgen status variably include high body fat percentage, low muscle strength and biomarkers of the metabolic syndrome. Reducing exposure to factors that adversely affect androgen status may improve the general health of ageing men by mechanisms yet to be defined.

It has been known for many years that serum PTH rises with age, and it has been suggested that this rise may contribute to bone loss in postmenopausal women. It has been variously attributed to declining renal function, declining calcium absorption efficiency, and declining serum 25-hydroxyvitamin D [25(OH)D] levels. We studied the effects of age, weight, renal function, radiocalcium absorption, serum ionized calcium, and serum 25(OH)D on serum PTH levels in 918 postmenopausal women attending an osteoporosis center. On simple linear regression, serum PTH was a positive function of age (P = 0.003) and weight (P < 0.001) and an inverse function of serum 25(OH)D (P < 0.001) and serum ionized calcium (P = 0.002). On stepwise regression, serum 25(OH)D was the most significant (negative) determinant of serum PTH, followed in decreasing order of significance by serum ionized calcium (negative) and body weight and age (positive). Serum PTH was not related to radiocalcium absorption. The reciprocal relation between serum PTH and serum 25(OH)D could not be explained by the serum concentration of 1,25-dihydroxyvitamin D, which did not change with age. After adjustment for serum ionized calcium, body weight, and age, the rise in serum PTH appeared to start when serum 25(OH)D fell less than 80 nmol/liter.

OBJECTIVE To evaluate the effects of the menopause on bone-related biochemical variables in a longitudinal study. DESIGN Recruitment by advertisement of premenopausal women over the age of 44 for measurement of selected variables and collection of blood and urine samples for deep freezing, followed by annual check of menopausal status and repeat collection of blood and urine samples for deep freezing after the menopausal transition. PATIENTS A total of 104 women with confirmed premenopausal status and on no treatment likely to affect calcium or bone metabolism were admitted to the study over a period of 2 years. After 8 years, 43 of the volunteers had passed through the menopause and the study was closed. MEASUREMENTS Radiocalcium absorption was measured at the first attendance and again after the menopausal transition. Calcium and other relevant variables were measured consecutively on paired thawed-out samples of blood and urine. RESULTS The data were complete in 34 subjects. In these women, there were highly significant correlations between the first and second measurements of most variables - serum calcium and fractions, radiocalcium absorption, vitamin D metabolites, PTH and others - indicating significant 'tracking' of these variables across the menopause. Within that framework there were significant rises in serum total and calculated ionized calcium (both P < 0.001) without change in mean serum parathyroid hormone (PTH). Radiocalcium absorption fell (P < 0.001) without change in serum 1,25D. There was a rise in fasting urinary calcium (P < 0.001) which could not be explained by the rise in filtered load and therefore represented a fall in TmCa (P < 0.001). There were significant rises in urinary bone resorption markers, pyridinoline and deoxypyridinoline (P < 0.001). CONCLUSIONS We conclude that the menopausal rise in calculated serum ionized calcium without fall in PTH, indicates a change in PTH set-point, and that the falls in gastrointestinal absorption and renal tubular reabsorption of calcium reflect the loss of an oestrogen action at these two sites. Although these changes are sufficient to explain the rise in calcium requirement at the menopause, the association of high bone resorption with normal serum PTH suggests also an increased sensitivity of bone to the action of parathyroid hormone. There is significant 'tracking' of many variables across the menopause despite very significant changes in their absolute values.

We have examined the relation between radiocalcium absorption and serum 1,25-dihydroxy-vitamin D [1,25(OH)2D3] levels in a set of 60 postmenopausal women on corticosteroid therapy (29 with and 31 without vertebral compression fractures) and compared these results with those from 31 normal postmenopausal women age-matched with the “normal” corticosteroid-treated women. Radiocalcium absorption was a function of serum 1,25(OH)2D3 in both corticosteroid-treated groups and in the set as a whole, but the impaired calcium absorption in the corticosteroid-treated patients with osteoporosis was not accounted for by their slightly reduced serum 1,25(OH)2D3 levels. This apparent resistance to the intestinal action of 1,25(OH)2D3 was quantified by a Z score which expresses, in standard deviation units, the difference between the measured calcium absorption and that predicted from the 1,25(OH)2D3 level. The Z score was significantly reduced in the osteoporotic group. Vertebral mineral density (VMD) was measured by quantitative computed tomography in 43 of the corticosteroid-treated cases and in all the normal postmenopausal women; analysis by VMD yielded similar conclusions.