Kieran A. McCaul

Low Free Testosterone Predicts Frailty in Older Men: The Health in Men Study

CONTEXT The prevalence of frailty increases, whereas testosterone decreases, as men age. Low testosterone may be a risk factor for development of this syndrome. OBJECTIVE Our objective was to determine whether testosterone levels are associated with frailty. DESIGN We conducted a prospective cohort study. SETTING AND PARTICIPANTS Between 2001 and 2004, frailty was assessed in 3616 community-dwelling men aged 70-88 yr. Frailty was reassessed in 1586 men aged 76-93 yr in 2008-2009. MAIN OUTCOME MEASURES Frailty was assessed with the FRAIL scale, comprising five domains: fatigue, difficulty climbing a flight of stairs, difficulty walking more than 100 m, more than five illnesses present, or weight loss greater than 5%. Testosterone, SHBG, and LH were assayed at baseline. Free testosterone was calculated using mass action equations. RESULTS At baseline, 15.2% of men (n = 548) were frail (at least three deficits), increasing to 23.0% (n = 364) at follow-up. At baseline, each 1 sd decrease in total or free testosterone level was associated with increased odds of frailty [odds ratio (OR) = 1.23; 95% confidence interval (CI) = 1.11-1.38, and OR = 1.29; 95% CI = 1.15-1.44 for total and free testosterone, respectively]. Lower LH was associated with reduced odds of frailty (OR = 0.88; 95% CI = 0.81-0.95). Adjustments were made for age, body mass index, smoking, diabetes, social support, and other covariates. At follow-up, only lower free testosterone levels (OR = 1.22; 95% CI = 1.05-1.42) predicted frailty. CONCLUSIONS Lower free testosterone was independently associated with frailty at baseline and follow-up. Randomized trials should explore whether testosterone therapy can prevent the development of frailty.

Body mass index and survival in men and women aged 70 to 75

OBJECTIVES: To examine in an older population all‐cause and cause‐specific mortality associated with underweight (body mass index (BMI)<18.5), normal weight (BMI 18.5–24.9), overweight (BMI 25.0–29.9), and obesity (BMI≥30.0).

Homocysteine and Depression in Later Life

CONTEXT The prevalence of depression in later life increases with plasma total homocysteine concentration (tHcy). High tHcy accounts for about 15% of prevalent cases, but observational studies are prone to confounding and bias. Genetic association studies are not prone to the same sources of error and offer an opportunity to explore the consistency and external validity of this association. OBJECTIVE To determine if tHcy is causally related to depression in later life. DESIGN Cross-sectional study (Health in Men Study), systematic review, and meta-analysis. Patients Community sample of 3752 men aged 70 years or older (Health in Men Study). MAIN OUTCOME MEASURES Fifteen-Item Geriatric Depression Scale and self-reported past or current treatment for depression (Health in Men Study). RESULTS In the Health in Men Study, the odds ratio (OR) of prevalent depression increased 4% (OR, 1.04; 95% confidence interval [CI], 1.02-1.05) with every unit increase of tHcy (micromoles per liter). The tHcy was 0.19 mg/L higher among participants with the MTHFR C677T TT genotype compared with the CC genotype. The meta-analysis showed that older adults with high tHcy had increased risk of depression (OR, 1.70; 95% CI, 1.38-2.08) and TT carriers were 22% more likely than CC carriers to have current depression or a history of depression (OR, 1.22; 95% CI, 1.01-1.47). CONCLUSIONS The triangular association between the MTHFR genotype, tHcy, and depression implies that higher concentrations of tHcy increase the risk of depression and that lowering tHcy by 0.19 mg/L could reduce the odds of depression by about 20%. Confirmatory data from sufficiently powered randomized trials of homocysteine-lowering therapy are now required to test if the relationship between tHcy and depression is truly causal.

Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels

OBJECTIVE Bone-derived undercarboxylated osteocalcin regulates insulin secretion and sensitivity in mice, and reduced serum total osteocalcin (TOC) is associated with diabetes in humans. However, the relationship between TOC levels and other cardiovascular risk factors is uncertain. We sought to determine whether serum TOC is associated with metabolic syndrome and its components in older men. DESIGN Cross-sectional analysis from a population-based cohort of men aged >or=70 years. METHODS Early morning sera were assayed for TOC. Insulin resistance was estimated using a homeostatic model (HOMA2-IR). Metabolic syndrome was defined according to NCEP-ATPIII criteria. RESULTS TOC was assayed in 4047 men. Men who were not fasting and reported having bone fractures, Pagets disease, or bisphosphonate, glucocorticoid, or warfarin use were excluded, leaving 2765 men with metabolic syndrome present in 797 (28.8%). TOC was inversely associated with waist circumference, glucose, and triglyceride levels and HOMA2-IR (all P<0.001), and was lower in men with metabolic syndrome (mean+/-S.E.M.: 20.1+/-0.4 vs 21.4+/-0.2 microg/l, P=0.002). In multivariate analysis, men with TOC of 13.25-16.55 and <13.25 microg/l had 1.5- to 2-fold increased risk of metabolic syndrome compared with men with levels >or=30 microg/l. TOC remained associated with metabolic syndrome after adjustment for individual components, but not after adjusting for both waist circumference and glucose. CONCLUSIONS Increased waist circumference, reduced TOC, elevated glucose, and triglyceride levels are inter-related in aging men. Osteocalcin may lie in the causal pathway between central adiposity and insulin resistance. Further research is required to evaluate whether interventions which raise osteocalcin levels might decrease cardiovascular risk.

Low Free Testosterone Predicts Mortality from Cardiovascular Disease But Not Other Causes: The Health in Men Study

CONTEXT Low testosterone is associated with all-cause mortality, but the relationship with cause-specific mortality is uncertain. OBJECTIVE Our objective was to explore associations between testosterone and its related hormones and cause-specific mortality. DESIGN This was a population-based cohort study. SETTING AND PARTICIPANTS Demographic and clinical predictors of mortality, and testosterone, SHBG, and LH were measured from 2001-2004 in 3637 community-dwelling men aged 70-88 yr (mean, 77 yr). MAIN OUTCOME MEASURE Cause of death was obtained via electronic record linkage until December 31, 2008. RESULTS During a mean follow-up period of 5.1 yr, there were 605 deaths. Of these, 207 [34.2%; 95% confidence interval (CI) = 30.4-38.1%] were due to cardiovascular disease (CVD), 231 to cancer (38.2%; 95% CI = 34.3-42.1%), 130 to respiratory diseases (21.5%; 95% CI = 18.2-24.8%), and 76 to other causes (12.6%; 95% CI = 9.9-15.2%). There were 39 deaths attributable to both cancer and respiratory diseases. Lower free testosterone (hazard ratio = 1.62; 95% CI = 1.20-2.19, for 100 vs. 280 pmol/liter), and higher SHBG and LH levels were associated with all-cause mortality. In cause-specific analyses, lower free testosterone (sub-hazard ratio = 1.71; 95% CI = 1.12-2.62, for 100 vs. 280 pmol/liter) and higher LH predicted CVD mortality, while higher SHBG predicted non-CVD mortality. Higher total testosterone and free testosterone levels (sub-hazard ratio = 1.96; 95% CI = 1.14-3.36, for 400 vs. 280 pmol/liter) were associated with mortality from lung cancer. CONCLUSIONS Low testosterone predicts mortality from CVD but is not associated with death from other causes. Prevention of androgen deficiency might improve cardiovascular outcomes but is unlikely to affect longevity otherwise.

RESTRICTIONS ON SMOKING AT HOME AND URINARY COTININE LEVELS AMONG CHILDREN WITH ASTHMA

OBJECTIVES The purpose of this study was to determine the extent to which various levels of restrictions on smoking in the home may be associated with childrens exposure to environmental tobacco smoke (ETS). METHODS The methodology consisted of a cross-sectional survey involving 249 children with asthma aged 1 to 11 attending hospital outpatient clinics, with at least one parent who smoked, linked to the childs urinary cotinine to creatinine ratios (CCR). RESULTS After adjustment for childs age, mothers smoking status, and total parental daily cigarette consumption, a total ban was associated with significantly lower urinary CCR levels (7.6 nmol/mmol) than bans with exceptions or limited smoking in the home. Where exceptions to bans were made (14.9 nmol/mmol), childrens urinary CCR levels were no different from homes in which smoking was allowed in rooms the child rarely frequented (14.1 nmol/mmol). These two intermediate levels of restriction were in turn associated with significantly lower CCR levels than unrestricted smoking in the home (26.0 nmol/mmol). CONCLUSIONS Making exceptions to bans on smoking at home measurably undermines the protective effect of a ban. However, making some exceptions to a ban and limiting smoking to rooms where the child rarely goes may result in reduced exposure to ETS, compared with unrestricted smoking.

Physical activity and all-cause mortality in older women and men

Background Regular physical activity is associated with reduced risk of mortality in middle-aged adults; however, associations between physical activity and mortality in older people have been less well studied. The objective of this study was to compare relationships between physical activity and mortality in older women and men. Methods The prospective cohort design involved 7080 women aged 70–75 years and 11 668 men aged 65–83 years at baseline, from two Australian cohorts – the Australian Longitudinal Study on Womens Health and the Health in Men Study. Self-reported low, moderate and vigorous intensity physical activity, socio-demographic, behavioural and health characteristics were assessed in relation to all-cause mortality from the National Death Index from 1996 to 2009; the median follow-up of 10.4 (women) and 11.5 (men) years. Results There were 1807 (25.5%) and 4705 (40.3%) deaths in women and men, respectively. After adjustment for behavioural risk factors, demographic variables and self-reported health at baseline, there was an inverse dose – response relationship between physical activity and all-cause mortality. Compared with women and men who reported no activity, there were statistically significant lower hazard ratios for women who reported any activity and for men who reported activities equivalent to at least 300 metabolic equivalent.min/week. Risk reductions were 30–50% greater in women than in men in every physical activity category. Conclusions Physical activity is inversely associated with all-cause mortality in older men and women. The relationship is stronger in women than in men, and there are benefits from even low levels of activity.

Falls, injuries from falls, health related quality of life and mortality in older adults with vision and hearing impairment—Is there a gender difference?

BACKGROUND Vision and hearing decline with age. Loss of these senses is associated with increased risk of falls, injuries from falls, mortality and decreased health-related quality of life (HRQOL). Our objective was to determine if there are gender differences in the associations between visual and hearing impairment and these outcomes. METHODS 2340 men and 3014 women aged 76-81 years from the Health in Men Study and the Australian Longitudinal Study on Womens Health were followed for an average of 6.36 years. Dependent variables were self-reported vision and hearing impairment. Outcome variables were falls, injuries from falls, physical and mental components of HRQOL (SF-36 PCS and MCS) and all-cause mortality. RESULTS Vision impairment was more common in women and hearing impairment was more common in men. Vision impairment was associated with increased falls risk (odds ratio (OR)=1.77, 95% CI=1.35-2.32 in men; OR=1.82, 95% CI=1.44-2.30 in women), injuries from falls (OR=1.69, 95% CI=1.23-2.34 in men, OR=1.79, 95% CI=1.38-2.33 in women), and mortality (hazard ratio (HR)=1.44; 95% CI=1.17-1.77 in men; HR=1.50, 95% CI=1.24-1.82 in women) and declines in SF-36 PCS and MCS. Hearing impairment was associated with increased falls risk (OR=1.38, 95% CI=1.08-1.78 in men; OR=1.45, 95% CI=1.08-1.93 in women) and declines in SF-36 PCS and MCS. Overall there were no gender differences in the association between vision and hearing impairment and the outcomes. CONCLUSION In men and women aged 76-81 years, there were no gender differences in the association between self-reported vision and hearing impairment and the outcomes of falls, mortality and HRQOL.

Prevalence of sexual activity and associated factors in men aged 75 to 95 years: a cohort study.

BACKGROUND Knowledge about sexuality in elderly persons is limited, and normative data are lacking. OBJECTIVE To determine the proportion of older men who are sexually active and to explore factors predictive of sexual activity. DESIGN Population-based cohort study. SETTING Community-dwelling men from Perth, Western Australia, Australia. PARTICIPANTS 3274 men aged 75 to 95 years. MEASUREMENTS Questionnaires from 1996 to 1999, 2001 to 2004, and 2008 to 2009 assessed social and medical factors. Sex hormones were measured from 2001 to 2004. Sexual activity was assessed by questionnaire from 2008 to 2009. RESULTS A total of 2783 men (85.0%) provided data on sexual activity. Sex was considered at least somewhat important by 48.8% (95% CI, 47.0% to 50.6%), and 30.8% (CI, 29.1% to 32.5%) had had at least 1 sexual encounter in the past 12 months. Of the latter, 56.5% were satisfied with the frequency of activity, whereas 43.0% had sex less often than preferred. In cross-sectional analyses, increasing age, partners lack of interest, partners physical limitations, osteoporosis, prostate cancer, diabetes, antidepressant use, and β-blocker use were independently associated with reduced odds of sexual activity. Living with a partner and having a non-English-speaking background were associated with increased odds. In longitudinal analyses, higher testosterone levels were associated with increased odds of being sexually active. Other factors were similar to the cross-sectional model. LIMITATIONS Response bias may have influenced findings because sexuality can be a sensitive topic. Attrition may have resulted in a healthier-than-average sample of older men. CONCLUSION One half of elderly men consider sex important, and one third report being sexually active. Mens health problems were associated with lack of sexual activity. Key modifiable risk factors include diabetes, depression, and medication use. Endogenous testosterone levels predict sexual activity, but the role of testosterone therapy remains uncertain. PRIMARY FUNDING SOURCE National Health and Medical Research Council of Australia.

The effect of a smoke-free law on restaurant business in South Australia

Background: Despite evidence to the contrary from overseas research, the introduction of smoke‐free legislation in South Australia (SA), which required all restaurants to go smoke‐free in January 1999, sparked concerns among the hospitality industry about loss of restaurant business. This study aimed to determine whether the law had a detrimental impact on restaurant business in SA.