Zoë Hyde

Cohort Profile: The Health In Men Study (HIMS)

The Health In Men Study (HIMS) arose out of a population-based randomized trial of screening for abdominal aortic aneurysms (AAAs) conducted in Perth, Western Australia in 1996–99. Only men aged 65 years and over were recruited into the trial as AAAs are uncommon below this age and are six times more common in men than women. The aim of the trial was to assess whether screening reduced mortality from AAA. Secondary outcomes included assessments of the impact of screening on all-cause mortality and quality of life and a study of the rates of expansion of screen-detected AAAs.

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.

Lower sex hormone-binding globulin is more strongly associated with metabolic syndrome than lower total testosterone in older men: the Health in Men Study.

BACKGROUND Reduced circulating testosterone and sex hormone-binding globulin (SHBG) are implicated as risk factors for metabolic syndrome. As SHBG increases with age while testosterone declines, we examined the relative contributions of SHBG and testosterone to the risk of metabolic syndrome in older men. METHODS We conducted a cross-sectional study of 2502 community-dwelling men aged > or = 70 years without known diabetes. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) criteria. Early morning fasting sera were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using mass action equations. RESULTS There were 602 men with metabolic syndrome (24.1%). The risk of metabolic syndrome increased for total testosterone < 20 nmol/l, SHBG < 50 nmol/l and free testosterone < 300 pmol/l. In univariate analyses SHBG was associated with all five components of metabolic syndrome, total testosterone was associated with all except hypertension, and free testosterone was associated only with waist circumference and triglycerides. In multivariate analysis, both total testosterone and especially SHBG remained associated with metabolic syndrome, with odds ratios of 1.34 (95% confidence interval (CI): 1.18-1.52) and 1.77 (95% CI: 1.53-2.06) respectively. Men with hypogonadotrophic hypogonadism (total testosterone < 8 nmol/l, LH < or = 12 IU/l) had the highest prevalence of metabolic syndrome (53%, P<0.001). CONCLUSIONS Lower SHBG is more strongly associated with metabolic syndrome than lower total testosterone in community-dwelling older men. SHBG may be the primary driver of these relationships, possibly reflecting its relationship with insulin sensitivity. Further studies should examine whether measures that raise SHBG protect against the development of metabolic syndrome in older men.

Lower serum testosterone is independently associated with insulin resistance in non-diabetic older men: the Health In Men Study.

OBJECTIVE Insulin resistance is associated with metabolic syndrome and type 2 diabetes, representing a risk factor for cardiovascular disease. This relationship may be modulated to some extent by age-related changes in sex hormone status. We examined whether lower testosterone or sex hormone-binding globulin (SHBG) levels in older men are associated with insulin resistance independently of measures of central obesity. DESIGN Cross-sectional analysis of 2470 community-dwelling non-diabetic men aged > or = 70 years. METHODS Age, body mass index (BMI) and waist circumference were measured. Early morning sera were assayed for total testosterone, SHBG, LH and insulin levels. Free testosterone was calculated using mass action equations, and insulin resistance was assessed using a homeostatic model (HOMA2-IR). RESULTS Total testosterone, free testosterone and SHBG declined progressively across increasing quintiles of HOMA2-IR (all P<0.001) and correlated inversely with log HOMA2-IR (r=-0.27, -0.14 and -0.24 respectively, all P<0.001). After adjusting for age, BMI, waist circumference, high-density lipoprotein and triglyceride levels, total testosterone was independently associated with log HOMA2-IR (beta=0.05, P<0.001), while SHBG was not. Serum total testosterone <8 nmol/l was associated with HOMA2-IR in the highest quintile (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.02-2.73) as was total testosterone > or = 8 and <15 nmol/l (OR 1.29, 95% CI 1.03-1.63). CONCLUSIONS In older men, lower total testosterone is associated with insulin resistance independently of measures of central obesity. This association is seen with testosterone levels in the low to normal range. Further studies are needed to evaluate interventions that raise testosterone levels in men with reduced insulin sensitivity.

Quality use of medicines and health outcomes among a cohort of community dwelling older men: an observational study.

AIM To determine the prevalence of potentially suboptimal medication use and association with adverse outcomes. METHODS A prospective, observational cohort study of 4260 community-dwelling older men from Perth, Western Australia (mean age of 77 ± 3.6 years) was conducted. Follow-up was for 4.5 years (or until death, if sooner). Cox proportional hazard models were used to explore associations between suboptimal medication use and prospective clinical outcomes. Logistic regression analyses were used to explore predictors of a fall in the previous 12 months. RESULTS Use of potentially inappropriate medicines (48.7%), polypharmacy (≥5 medications, 35.8%) and potential under-utilization (56.7%) were highly prevalent, and overall 82.3% of participants reported some form of potentially suboptimal medication use. A self-reported history of falls in the previous 12 months was independently associated with the number of medicines taken (odds ratio [OR]= 1.06, 95% confidence interval [CI] 1.02, 1.09) and use of one or more potentially inappropriate medicines (OR = 1.23, 95% CI 1.04, 1.45). After adjusting for age, co-morbidity, smoking status, body mass index, hypertension and educational attainment, the number of medicines reported was associated with admission to hospital (hazard ratio [HR]= 1.04, 95% CI 1.03, 1.06), cardiovascular events (HR = 1.09, 95% CI 1.06, 1.12) and all cause mortality (HR = 1.04, 95% CI 1.00, 1.07). Use of one or more potentially inappropriate medicines was associated with admission to hospital (HR = 1.16, 95% CI 1.08, 1.24). Potential under-utilization was associated with cardiovascular events (HR = 1.20, 95% CI 1.03, 1.40). CONCLUSIONS These data suggest that both medication over-use and under-use occur frequently among older men and may be harmful.

Higher serum free testosterone is associated with better cognitive function in older men, while total testosterone is not. The Health In Men Study.

Objective  To determine the relationship of total and free serum testosterone to cognitive performance in older men.

Healthier lifestyle predicts higher circulating testosterone in older men : the Health In Men Study

Objective  Circulating testosterone declines during male ageing, and low testosterone may predispose to ill health. We sought to determine whether greater participation in healthy behaviours predicted reduced risk of subsequent lower circulating testosterone in older men.

Prevalence and Predictors of Sexual Problems in Men Aged 75–95 Years: A Population-Based Study

INTRODUCTION Hypogonadism is associated with impaired libido and erectile dysfunction in young men, but the causes of sexual dysfunction in older men are less well understood. AIM To determine the prevalence and predictors of sexual problems in older men. MAIN OUTCOME MEASURE Sexual problems, as assessed by a self-reported questionnaire. METHODS This was a population-based, cohort study of 3,274 community-dwelling men aged 75-95 years (mean 82 years) from Perth, Western Australia. Questionnaires in 2001-2004 and 2008-2009 assessed social and medical risk factors. Sex hormones were measured in 2001-2004. Predictors of sexual problems, measured in 2008-2009, were assessed cross-sectionally in the entire sample, and longitudinally in a subset of 1,744 men with sex hormone data. RESULTS Sexual problems were highly prevalent, with 49.4% (95% confidence interval 47.7% to 51.1%) reporting erectile problems, 47.7% (45.9% to 49.4%) lacking interest in sexual activity, 38.7% (37.0% to 40.3%) unable to climax, and 20.4% (19.1% to 21.8%) anxious about their ability to perform sexually. Painful and unpleasurable sex were less common (<5%). Overall, 72.0% (70.5% to 73.6%) reported at least one problem. In multivariate binary logistic regression analyses, cardiovascular disease, diabetes, depression, prostate disorders, and insomnia were the factors most commonly associated with sexual problems. Low testosterone levels were associated with lack of interest in sex, but not with other complaints. CONCLUSIONS Sexual problems are common in elderly men. Chronic disease, depression, and insomnia appear to be the main modifiable risk factors. Androgen deficiency is unlikely to be a major cause of sexual problems in this age group.

Associations between Testosterone Levels and Incident Prostate, Lung, and Colorectal Cancer. A Population-Based Study

Background: The relationship between testosterone and cancer is relatively unexplored. We sought to examine whether testosterone and related hormones are associated with incident prostate, lung, and colorectal cancer. Methods: This was a population-based cohort study. Demographic and clinical predictors of cancer, and testosterone, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured between 2001 and 2004 in 3,635 community-dwelling men aged 70 to 88 years (mean 77 years). Cancer notifications were obtained via electronic record linkage until December 31, 2010. Results: During a mean follow-up period of 6.7 ± 1.8 years, there were 297, 104, and 82 cases of prostate, colorectal, and lung cancer. In adjusted competing risks proportional hazards models, each one SD increase in free testosterone was associated with a 9% increase in prostate cancer risk (95% confidence interval [CI], 1.00–1.18), but other hormones were not significantly associated. No significant associations were observed between hormonal parameters and colorectal cancer. Higher total testosterone was associated with lung cancer. Compared with the mean of 15 nmol/L, men with levels of 20 nmol/L were 1.38 times more likely to be cases (95% CI, 1.21–1.57), whereas those with levels of 30 nmol/L were 3.62 times more likely to be cases (95% CI, 2.53–5.18). Higher free testosterone was also associated with lung cancer, though SHBG and LH were not. Associations were maintained after exclusion of current smokers. Conclusions: Higher free testosterone was associated with incident prostate cancer. Higher testosterone levels may also be associated with lung cancer. Impact: Further studies should investigate whether these risks apply to men receiving testosterone therapy. Cancer Epidemiol Biomarkers Prev; 21(8); 1319–29. ©2012 AACR.

Higher Luteinizing Hormone is Associated with Poor Memory Recall: The Health in Men Study

Elevated levels of gonadotropins have been observed in patients with Alzheimers disease and have been associated with poorer cognition in women, but not men. The aim of this study was to explore the relationship between gonadotropins and cognition in a cohort of 585 healthy, community-dwelling men aged 70-87 years. Cognitive function was assessed with the California Verbal Learning Test Second Edition (CVLT-II) and the Standardized Mini-Mental State Examination (SMMSE). Testosterone, sex hormone binding globulin, and luteinizing hormone levels were assayed from early morning sera. Free testosterone was calculated using mass action equations. In linear regression analyses, neither total nor free testosterone levels were associated with measures of immediate or delayed recall. Higher levels of luteinizing hormone were associated with poorer performance on a measure of immediate recall (CVLT-II trials 1-5 total score) independent of total and free testosterone levels. The association remained after adjustment for age, educational attainment, and depression. In contrast, only total and free testosterone levels were associated with SMMSE score. These findings suggest a role for both androgens and gonadotropins in differing cognitive domains, and that gonadotropins may influence cognition independent of sex steroids.