Hyponatremia, hypernatremia and impairment of functional, psychological and sexual domains.

OBJECTIVE: To determine the influence of serum sodium on physical, psychologic and sexual function. METHODS: This is a cross-sectional survey on 3340 community-dwelling men aged 40-79 years from a prospective cohort study in eight European countries, the European Male Ageing Study (EMAS). Participants filled-out the Short Form-36 (SF-36), the Physical Activity Scale for the Elderly (PASE), and the EMAS sexual function questionnaire. For all the analyses, serum sodium corrected for glycaemia ([Na+]G) was used. RESULTS: The relationship between [Na+]G and SF-36 physical function score (F = 3.99; p = 0.01), SF-36 mental health score (F = 7.69; p < 0.001), and PASE score (F = 14.95; p < 0.001) were best described by a quadratic equation, with worse scores for [Na+]G in either the lowest or the highest ends of the range. After dividing the sample into [Na+]G < 136 mmol/L (n = 81), 136-147 mmol/L (n = 3223) and > 147 mmol/L (n = 36), linear regression analyses with linear spline functions adjusted for confounders did not confirm these relationships. Similarly, erectile dysfunction and [Na+]G, were in a quadratic relationship (F = 9.00; p < 0.001). After adjusting for confounders, the linear regression with spline functions denoted a significantly worsened erectile function for increases in serum [Na+]G > 147 mmol/L (B = 0.15 [0.04;0.26], p < 0.01) but no relationship with [Na+]G < 136 mmol/L. Likewise, the relationship of [Na+]G with concerns about sexual dysfunction was confirmed only for men with serum [Na+]G > 147 mmol/L. CONCLUSIONS: This is the first study supporting an association between [Na+]G and sexual function. A worsening of erection and concerns about sexual function were observed for the highest values of [Na+]G, independently of other relevant factors.

Salivary Testosterone Levels and Health Status in Men and Women in the British General Population: Findings from the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

CONTEXT: Salivary T (Sal-T) measurement by liquid chromatography-tandem mass spectroscopy resents the opportunity to examine health correlates of Sal-T in a large-scale population survey. OBJECTIVE: This study sought to examine associations between Sal-T and health-related factors in men and women age 18-74 years. DESIGN AND SETTING: Morning saliva samples were obtained from participants in a cross-sectional probability-sample survey of the general British population (Natsal-3). Self-reported health and lifestyle questions were administered as part of a wider sexual health interview. PARTICIPANTS: Study participants included 1599 men and 2123 women. METHODS: Sal-T was measured using liquid chromatography-tandem mass spectroscopy. Linear regression was used to examine associations between health factors and mean Sal-T. RESULTS: In men, mean Sal-T was associated with a range of health factors after age adjustment, and showed a strong independent negative association with body mass index (BMI) in multivariable analysis. Men reporting cardiovascular disease or currently taking medication for depression had lower age-adjusted Sal-T, although there was no association with cardiovascular disease after adjustment for BMI. The decline in Sal-T with increasing age remained after adjustment for health-related factors. In women, Sal-T declined with increasing age; however, there were no age-independent associations with health-related factors or specific heath conditions with the exception of higher Sal-T in smokers. CONCLUSIONS: Sal-T levels were associated, independently of age, with a range of self-reported health markers, particularly BMI, in men but not women. The findings support the view that there is an age-related decline in Sal-T in men and women, which cannot be explained by an increase in ill health. Our results demonstrate the potential of Sal-T as a convenient measure of tissue androgen exposure for population research.

Ethnic differences in bone geometry between White, Black and South Asian men in the UK.

Relatively little is known about the bone health of ethnic groups within the UK and data are largely restricted to women. The aim of this study was to investigate ethnic differences in areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), bone geometry and strength in UK men. White European, Black Afro-Caribbean and South Asian men aged over 40years were recruited from Greater Manchester, UK. aBMD at the spine, hip, femoral neck and whole body were measured by DXA. Bone geometry, strength and vBMD were measured at the radius and tibia using pQCT at the metaphysis (4%) and diaphysis (50% radius; 38% tibia) sites. Adjustments were made for age, weight and height. Black men had higher aBMD at the whole body, total hip and femoral neck compared to White and South Asian men independent of body size adjustments, with no differences between the latter two groups. White men had longer hip axis lengths than both Black and South Asian men. There were fewer differences in vBMD but White men had significantly lower cortical vBMD at the tibial diaphysis than Black and South Asian men (p<0.001). At the tibia and radius diaphysis, Black men had larger bones with thicker cortices and greater bending strength than the other groups. There were fewer differences between White and South Asian men. At the metaphysis, South Asian men had smaller bones (p=0.02) and lower trabecular vBMD at the tibia (p=0.003). At the diaphysis, after size-correction, South Asian men had similar sized bones but thinner cortices than White men; measures of strength were not broadly reduced in the South Asian men. Combining pQCT and DXA measurements has given insight into differences in bone phenotype in men from different ethnic backgrounds. Understanding such differences is important in understanding the aetiology of male osteoporosis.

Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study.

We examined cross-sectional associations of metabolic syndrome and its components with male bone turnover, density and structure. Greater bone mass in men with metabolic syndrome was related to their greater body mass, whereas hyperglycaemia, hypertriglyceridaemia or impaired insulin sensitivity were associated with lower bone turnover and relative bone mass deficits. INTRODUCTION: Metabolic syndrome (MetS) has been associated with lower bone turnover and relative bone mass or strength deficits (i.e. not proportionate to body mass index, BMI), but the relative contributions of MetS components related to insulin sensitivity or obesity to male bone health remain unclear. METHODS: We determined cross-sectional associations of MetS, its components and insulin sensitivity (by homeostatic model assessment-insulin sensitivity (HOMA-S)) using linear regression models adjusted for age, centre, smoking, alcohol, and BMI. Bone turnover markers and heel broadband ultrasound attenuation (BUA) were measured in 3129 men aged 40-79. Two centres measured total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD, n = 527) and performed radius peripheral quantitative computed tomography (pQCT, n = 595). RESULTS: MetS was present in 975 men (31.2 %). Men with MetS had lower ß C-terminal cross-linked telopeptide (ß-CTX), N-terminal propeptide of type I procollagen (PINP) and osteocalcin (P < 0.0001) and higher total hip, femoral neck, and lumbar spine aBMD (P ≤ 0.03). Among MetS components, only hypertriglyceridaemia and hyperglycaemia were independently associated with PINP and ß-CTX. Hyperglycaemia was negatively associated with BUA, hypertriglyceridaemia with hip aBMD and radius cross-sectional area (CSA) and stress-strain index. HOMA-S was similarly associated with PINP and ß-CTX, BUA, and radius CSA in BMI-adjusted models. CONCLUSIONS: Men with MetS have higher aBMD in association with their greater body mass, while their lower bone turnover and relative deficits in heel BUA and radius CSA are mainly related to correlates of insulin sensitivity. Our findings support the hypothesis that underlying metabolic complications may be involved in the bone's failure to adapt to increasing bodily loads in men with MetS.

Associations of obesity with socioeconomic and lifestyle factors in middle-aged and elderly men: European Male Aging Study (EMAS).

BACKGROUND: Social and lifestyle influences on age-related changes in body morphology are complex because lifestyle and physiological response to social stress can affect body fat differently. OBJECTIVE: In this study, we examined the associations of socioeconomic status (SES) and lifestyle factors with BMI and waist circumference (WC) in middle-aged and elderly European men. DESIGN AND SETTING: A cross-sectional study of 3319 men aged 40-79 years recruited from eight European centres. OUTCOMES: We estimated relative risk ratios (RRRs) of overweight/obesity associated with unfavourable SES and lifestyles. RESULTS: The prevalence of BMI ≥ 30 kg/m(2) or WC ≥ 102 cm rose linearly with age, except in the eighth decade when high BMI, but not high WC, declined. Among men aged 40-59 years, compared with non-smokers or most active men, centre and BMI-adjusted RRRs for having a WC between 94 and 101.9 cm increased by 1.6-fold in current smokers, 2.7-fold in least active men and maximal at 2.8-fold in least active men who smoked. Similar patterns but greater RRRs were observed for men with WC ≥ 102 cm, notably 8.4-fold greater in least active men who smoked. Compared with men in employment, those who were not in employment had increased risk of having a high WC by 1.4-fold in the 40-65 years group and by 1.3-fold in the 40-75 years group. These relationships were weaker among elderly men. CONCLUSION: Unfavourable SES and lifestyles associate with increased risk of obesity, especially in middle-aged men. The combination of inactivity and smoking was the strongest predictor of high WC, providing a focus for health promotion and prevention at an early age.

Late-onset hypogonadism and mortality in aging men.

CONTEXT: Late-onset hypogonadism (LOH) has recently been defined as a syndrome in middle-aged and elderly men reporting sexual symptoms in the presence of low T. The natural history of LOH, especially its relationship to mortality, is currently unknown. OBJECTIVE: The aim of this study was to clarify the associations between LOH, low T, and sexual symptoms with mortality in men. DESIGN, SETTING, AND PARTICIPANTS: Prospective data from the European Male Aging Study (EMAS) on 2599 community-dwelling men aged 40-79 years in eight European countries was used for this study. MAIN OUTCOME MEASURE(S): All-cause, cardiovascular, and cancer-related mortality was measured. RESULTS: One hundred forty-seven men died during a median follow-up of 4.3 years. Fifty-five men (2.1%) were identified as having LOH (31 moderate and 24 severe). After adjusting for age, center, body mass index (BMI), current smoking, and poor general health, compared with men without LOH, those with severe LOH had a 5-fold [hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.7, 11.4] higher risk of all-cause mortality. Compared with eugonadal men, the multivariable-adjusted risk of mortality was 2-fold higher in those with T less than 8 nmol/L (irrespective of symptoms; HR 2.3; 95% CI 1.2, 4.2) and 3-fold higher in those with three sexual symptoms (irrespective of serum T; compared with asymptomatic men; HR 3.2; 95% CI 1.8, 5.8). Similar risks were observed for cardiovascular mortality. CONCLUSIONS: Severe LOH is associated with substantially higher risks of all-cause and cardiovascular mortality, to which both the level of T and the presence of sexual symptoms contribute independently. Detecting low T in men presenting with sexual symptoms offers an opportunity to identify a small subgroup of aging men at particularly high risk of dying.

Salivary testosterone measurement by liquid chromatography tandem mass spectrometry in adult males and females.

BACKGROUND: Salivary testosterone (Sal-T) may be a useful surrogate of serum free testosterone. The study aims were to use a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) assay to determine whether Sal-T concentrations accurately reflect Sal-T concentrations in both sexes and to investigate practical aspects of sample collection. METHODS: Saliva and serum samples were collected in 104 male and 91 female subjects. A more sensitive LC-MS/MS assay was developed to enable Sal-T quantitation in the low concentrations found in females. Saliva (200 µL) was extracted with 1 mL of methyl-tert-butyl ether following the addition of D5-testosterone. Quantitation was performed using a Waters TQ-S mass spectrometer. RESULTS: The assay achieved a lower limit of quantification of 5 pmol/L, sufficiently sensitive to measure testosterone in female saliva. Sal-T showed a diurnal variation but samples taken at weekly and monthly intervals showed no significant differences. Sal-T was stable at ambient temperature for up to 5 days, after freeze-thawing and 3 years frozen storage. Reference intervals for Sal-T were 93-378 pmol/L in males and 5-46 pmol/L in females. Sal-T correlated significantly with serum calculated free-T in males (r = 0.71, P < 0.001) and in females (r = 0.39, P < 0.001). CONCLUSIONS: These results confirm that testosterone can be reliably and accurately measured by LC-MS/MS in both adult male and female saliva samples. These results lay the foundation for further exploration of the clinical application of Sal- T as a reliable alternative to serum testosterone in the diagnosis and management of androgen disorders and assessment of androgen status in clinical research.

Obesity and weight management in the elderly: a focus on men.

The rising rate of overweight/obesity among the ever-growing ageing population is imposing massive and rapidly changing burdens of ill health. The observation that the BMI value associated with the lowest relative mortality is slightly higher in older than in younger adults, mainly through its reduced impact on coronary heart disease, has often been misinterpreted that obesity is not as harmful in the elderly, who suffer a large range of disabling consequences of obesity. All medical consequences of obesity are multi-factorial and most alleviated by modest, achievable weight loss (5-10 kg) with an evidence-based maintenance strategy. But severe obesity, e.g. BMI >40 may demand greater weight loss e.g. >15 kg to reverse type 2 diabetes. Since relatively reduced physical activity and reduced muscle mass (sarcopenic obesity) are common in the elderly, combining exercise and modest calorie restriction optimally reduces fat mass and preserves muscle mass - age presents no obstacle and reducing polypharmacy is a valuable outcome. The currently licensed drug orlistat has no age-related hazards and is effective in a low fat diet, but the risks from bariatric surgery begin to outweigh benefits above age 60. For the growing numbers of obese elderly with diabetes, the glucagon-like peptide-1 (GLP-1) receptor analogue liraglutide appears a safe way to promote and maintain substantial weight loss. Obesity and sarcopenia should be prevented from younger age and during life-transitions including retiral to improve future health outcomes and quality of life, with a focus on those in "obese families".

The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines.

Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study.

OBJECTIVE: Health and lifestyle factors are associated with variations in serum testosterone levels in ageing men. However, it remains unclear how age-related changes in testosterone may be attenuated by lifestyle modifications. The objective was to investigate the longitudinal relationships between changes in health and lifestyle factors with changes in hormones of the reproductive endocrine axis in ageing men. DESIGN: A longitudinal survey of 2736 community-dwelling men aged 40-79 years at baseline recruited from eight centres across Europe. Follow-up assessment occurred mean (±S.D.) 4.4±0.3 years later. RESULTS: Paired testosterone results were available for 2395 men. Mean (±S.D.) annualised hormone changes were as follows: testosterone -0.1±0.95  nmol/l; free testosterone (FT) -3.83±16.8  pmol/l; sex hormone-binding globulin (SHBG) 0.56±2.5  nmol/l and LH 0.08±0.57  U/l. Weight loss was associated with a proportional increase, and weight gain a proportional decrease, in testosterone and SHBG. FT showed a curvilinear relationship to weight change; only those who gained or lost ≥15% of weight showed a significant change (in the same direction as testosterone). Smoking cessation was associated with a greater decline in testosterone than being a non-smoker, which was unrelated to weight change. Changes in number of comorbid conditions or physical activity were not associated with significant alterations in hypothalamic-pituitary-testicular (HPT) axis function. CONCLUSIONS: Body weight and lifestyle factors influence HPT axis function in ageing. Weight loss was associated with a rise, and weight gain a fall, in testosterone, FT and SHBG. Weight management appears to be important in maintaining circulating testosterone in ageing men, and obesity-associated changes in HPT axis hormones are reversible following weight reduction.

Frailty Is Associated with Impaired Quality of Life and Falls in Middle-Aged and Older European Men.

OBJECTIVES: Adapt a measure of frailty for use in a cohort study of European men and explore relationships with age, health related quality of life and falls. DESIGN: Longitudinal cohort study. SETTING: 8 European centers. PARTICIPANTS: 3047 men aged 40-79 participating in the European Male Ageing Study (EMAS). MEASUREMENTS: Frailty was assessed using an adaptation of the Cardiovascular Health Study criteria. Health related quality of life was evaluated using the Rand Short Form-36 (SF-36) questionnaire which comprises both mental and physical component scores. Self reported falls in the preceding 12 months were recorded at 2-year follow-up. RESULTS: 78 men (2.6%) were classified as frail (≥3 criteria) and 821 (26.9%) as prefrail (1-2 criteria). The prevalence of frailty increased from 0.1% in men aged 40-49 up to 6.8% in men aged 70-79. Compared to robust men, both prefrail and frail men had lower health related quality of life. Frailty was more strongly associated with the physical than mental subscales of the SF-36. Frailty was associated with higher risk of falls OR (95% CI) 2.92 (1.52, 5.59). CONCLUSIONS: Frailty, assessed by the EMAS criteria, increased in prevalence with age and was related to poorer health related quality of life and higher risk of falls in middle-aged and older European men. These criteria may help to identify a vulnerable subset of older men.

Thyroid hormones and male sexual function.

The role of thyroid hormones in the control of erectile functioning has been only superficially investigated. The aim of the present study was to investigate the association between thyroid and erectile function in two different cohorts of subjects. The first one derives from the European Male Ageing Study (EMAS study), a multicentre survey performed on a sample of 3369 community-dwelling men aged 40-79 years (mean 60 ± 11 years). The second cohort is a consecutive series of 3203 heterosexual male patients (mean age 51.8 ± 13.0 years) attending our Andrology and Sexual Medicine Outpatient Clinic for sexual dysfunction at the University of Florence (UNIFI study). In the EMAS study all subjects were tested for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Similarly, TSH levels were checked in all patients in the UNIFI study, while FT4 only when TSH resulted outside the reference range. Overt primary hyperthyroidism (reduced TSH and elevated FT4, according to the reference range) was found in 0.3 and 0.2% of EMAS and UNIFI study respectively. In both study cohorts, suppressed TSH levels were associated with erectile dysfunction (ED). Overt hyperthyroidism was associated with an increased risk of severe erectile dysfunction (ED, hazard ratio = 14 and 16 in the EMAS and UNIFI study, respectively; both p < 0.05), after adjusting for confounding factors. These associations were confirmed in nested case-control analyses, comparing subjects with overt hyperthyroidism to age, BMI, smoking status and testosterone-matched controls. Conversely, no association between primary hypothyroidism and ED was observed. In conclusion, erectile function should be evaluated in all individuals with hyperthyroidism. Conversely, assessment of thyroid function cannot be recommended as routine practice in all ED patients.

Do androgens play any role in the physical frailty of ageing men?

The term frailty describes an age-related state of vulnerable health. The aetiology of this condition is not well understood. A number of mechanisms may contribute to frailty. Amongst these is the possible influence of age-related perturbations of sex hormones, particularly, the fall in testosterone in ageing men. This declining androgenic function has been thought to contribute to the loss of muscle mass (sarcopaenia) and strength that occurs with ageing and thereby underpin the development of frailty. Testosterone replacement has therefore been suggested as a possible intervention to treat frailty. This review summarizes evidence from observational and interventional studies on the effects of testosterone on frailty and its key components including body composition, muscle strength and physical function. Evidence from these studies is considered against study design, methodological issues and in the context of the current understanding of frailty. The role of androgens in the development of frailty and their utility in treating this condition are evaluated. Future research directions for the use of androgens in the treatment of frailty are suggested. The potential interaction between testosterone and other frailty mechanisms and the possibility that secondary components of the sex hormone system may be appropriate frailty biomarkers are also discussed.

Influence of age and sex steroids on bone density and geometry in middle-aged and elderly European men.

SUMMARY: The influence of age and sex steroids on bone density and geometry of the radius was examined in two European Caucasian populations. Age-related change in bone density and geometry was observed. In older men, bioavailable oestradiol may play a role in the maintenance of cortical and trabecular bone mineral density (BMD). INTRODUCTION: To examine the effect of age and sex steroids on bone density and geometry of the radius in two European Caucasian populations. METHODS: European Caucasian men aged 40-79 years were recruited from population registers in two centres: Manchester (UK) and Leuven (Belgium), for participation in the European Male Ageing Study. Total testosterone (T) and oestradiol (E(2)) were measured by mass spectrometry and the free and bioavailable fractions calculated. Peripheral quantitative computed tomography was used to scan the radius at distal (4%) and midshaft (50%) sites. RESULTS: Three hundred thirty-nine men from Manchester and 389 from Leuven, mean ages 60.2 and 60.0 years, respectively, participated. At the 50% radius site, there was a significant decrease with age in cortical BMD, bone mineral content (BMC), cortical thickness, and muscle area, whilst medullary area increased. At the 4% radius site, trabecular and total volumetric BMD declined with age. Increasing bioavailable E(2) (bioE(2)) was associated with increased cortical BMD (50% radius site) and trabecular BMD (4% radius site) in Leuven, but not Manchester, men. This effect was predominantly in those aged 60 years and over. In older Leuven men, bioavailable testosterone (Bio T) was linked with increased cortical BMC, muscle area and SSI (50% radius site) and total area (4% radius site). CONCLUSIONS: There is age-related change in bone density and geometry at the midshaft radius in middle-aged and elderly European men. In older men bioE(2) may maintain cortical and trabecular BMD. BioT may influence bone health through associations with muscle mass and bone area.

Chronic widespread pain is associated with slower cognitive processing speed in middle-aged and older European men.

Evidence from clinic-based studies suggests that the fibromyalgia syndrome (FMS) is associated with impairment in cognitive function though the mechanism is unclear. The aim of this analysis was to determine whether there is a similar association between chronic widespread pain (CWP), a cardinal feature of FMS, and impaired cognition in a community setting. Men (n=3369, 40-79 years) were recruited from population registers in eight centres for participation in the European Male Ageing Study (EMAS). The subjects completed a pain questionnaire and pain manikin, with the presence of CWP defined using the American College of Rheumatology criteria. The cognitive functions measured were visuospatial-constructional ability and visual memory (Rey-Osterrieth Complex Figure [ROCF]); visual recognition (Camden Topographical Recognition Memory test [CTRM]); and psychomotor processing speed (Digit-Symbol Substitution test [DSST]). We restricted our analysis to those subjects reporting pain that satisfied the criteria for CWP and those who were pain free. Of these 1539 men [mean (SD) age 60 (11) years], 266 had CWP. All cognitive test scores declined cross-sectionally with age (P<0.05). In age-adjusted linear regressions men with CWP had a lower DSST score (ß=-2.4, P<0.001) compared to pain-free subjects. After adjustment for lifestyle and health factors the association between pain status and the DSST score was attenuated but remained significant (ß=-1.02, P=0.04). There was no association between CWP and the ROCF-copy, ROCF-recall or CTRM scores. CWP is associated with slower psychomotor processing speed among community-dwelling European men. Prospective studies are required to confirm this observation and explore possible mechanisms for the association.

Gonadal sex steroid status and bone health in middle-aged and elderly European men.

SUMMARY: The influence of sex steroids on calcaneal quantitative ultrasound (QUS) parameters was assessed in a population sample of middle-aged and elderly European men. Higher free and total E(2) though not testosterone, were independently associated with higher QUS parameters. INTRODUCTION: The aim of this study was to investigate the association between QUS parameters and sex steroids in middle-aged and elderly European men. METHODS: Three thousand one hundred forty-one men aged between 40 and 79 years were recruited from eight European centres for participation in a study of male ageing: the European Male Ageing Study. Subjects were invited by letter to attend for an interviewer-administered questionnaire, blood sample and QUS of the calcaneus (Hologic-SAHARA). Blood was assessed for sex steroids including oestradiol (E(2)), testosterone (T), free and bio-available E(2) and T and sex hormone binding globulin (SHBG). RESULTS: Serum total T was not associated with any of the QUS parameters. Free T and both free and total E(2) were positively related to all QUS readings, while SHBG concentrations were negatively associated. These relationships were observed in both older and younger (<60 years) men. In a multivariate model, after adjustment for age, centre, height, weight, physical activity levels and smoking, free E(2) and SHBG, though not free T, remained independently associated with the QUS parameters. After further adjustment for IGF-1, however, the association with SHBG became non-significant. CONCLUSION: Higher free and total E(2) are associated with bone health not only among the elderly but also middle-aged European men.

Activational effects of sex hormones on cognition in men.

BACKGROUND: Changing world demographic patterns, such as the increasing number of older people and the growing prevalence of cognitive impairment, present serious obstacles to preserving the quality of life and productivity of individuals. The severity of dementia varies from subclinical, mild cognitive impairment to neurodegenerative diseases such as Alzheimer's. In normally ageing men, these age-related cognitive declines are accompanied by gradual but marked decreases in androgen levels and changes in other hormone profiles. While developmental effects of sex hormones on cognition in the pre- and early postnatal period have been demonstrated, their activational effects in later life are still a focus of contemporary research. Although there is a plethora of published research on the topic, results have been inconsistent with different studies reporting positive, negative or no effects of sex hormones on various aspects of mental agility. METHODS: This review summarizes the evidence supporting the biological plausibility of the activational effects of sex hormones upon cognition and describes the mechanisms of their actions. It offers a comprehensive summary of the studies of the effects of sex hormones on fluid intelligence in men utilizing elements from the Cochrane Collaboration Guidelines for Reviews. The results of both observational (cross-sectional and longitudinal) and interventional studies published to date are collated in table form and further discussed in the text. Factors contributing to the difficulties in understanding the effects of sex hormones on cognition are also examined. CONCLUSIONS: Although there is convincing evidence that steroid sex hormones play an organizational role in brain development in men, the evidence for activational effects of sex hormones affecting cognition in healthy men throughout adult life remains inconsistent. To address this issue, a new multifactorial approach is proposed which takes into account the status of other elements of the sex hormones axis including receptors, enzymes and other hormones.

ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males.

The new ISA, ISSAM, EAU, EAA and ASA recommendations on the investigation, treatment and monitoring of late-onset hypogonadism in males provide updated evidence-based information for clinicians who diagnose and treat patients with adult onset, age related testosterone deficiency.