F. C Wu

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.

Musculoskeletal frailty: A geriatric syndrome at the core of fracture occurrence in older age

A progressive decline in physiologic reserves inevitably occurs with ageing. Frailty results from reaching a threshold of decline across multiple organ systems. By consequence, frail elderly experience an excess vulnerability to stressors and are at high risk for functional deficits and comorbid disorders, possibly leading to institutionalization, hospitalization and death. The phenotype of frailty is referred to as the frailty syndrome and is widely recognized in geriatric medical practice. Although frailty affects both musculoskeletal and nonmusculoskeletal systems, sarcopenia, which is defined as age-related loss of muscle mass and strength, constitutes one of the main determinants of fracture risk in older age and one of the main components of the clinical frailty syndrome. As a result, operational definitions of frailty and therapeutic strategies in older patients tend to focus on the consequences of sarcopenia.

Scavenger receptor of class B expressed by osteoblastic cells are implicated in the uptake of cholesteryl ester and estradiol from LDL and HDL3.

Lipoproteins transport many vitamins and hormones that have been shown to be necessary for bone formation. However, the metabolism of LDL and HDL3 by bone‐forming osteoblastic cells remains unknown. Here we report that osteoblastic cells express scavenger receptors of class B that are implicated in the uptake of cholesterol and estradiol from LDL and HDL3.

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.

The androgen receptor gene CAG repeat in relation to 4-year changes in androgen-sensitive endpoints in community-dwelling older European men

CONTEXT The androgen receptor (AR) gene exon 1 CAG repeat length has been proposed to be a determinant of between-individual variations in androgen action in target tissues, which might regulate phenotypic differences of human ageing. However, findings on its phenotypic effects are inconclusive. OBJECTIVE To assess whether the AR CAG repeat length is associated with longitudinal changes in endpoints that are influenced by testosterone (T) levels in middle-aged and elderly European men. DESIGN Multinational European observational prospective cohort study. PARTICIPANTS A total of 1887 men (mean ± s.d. age: 63 ± 11 years; median follow up: 4.3 years) from centres of eight European countries comprised the analysis sample after exclusion of those with diagnosed diseases of the hypothalamic-pituitary-testicular (HPT) axis. MAIN OUTCOME MEASURES Longitudinal associations between the AR CAG repeat and changes in androgen-sensitive endpoints (ASEs) and medical conditions were assessed using regression analysis adjusting for age and centre. The AR CAG repeat length was treated as both a continuous and a categorical (6-20; 21-23; 24-39 repeats) predictor. Additional analysis investigated whether results were independent of baseline T or oestradiol (E2) levels. RESULTS The AR CAG repeat, when used as a continuous or a categorical predictor, was not associated with longitudinal changes in ASEs or medical conditions after adjustments. These results were independent of T and E2 levels. CONCLUSION Within a 4-year time frame, variations in the AR CAG repeat do not contribute to the rate of phenotypic ageing, over and above, which might be associated with the age-related decline in T levels.

Investigating the role of pain-modulating pathway genes in musculoskeletal pain

The aim of this study was to determine if genetic variation in the pain‐modulating gene DREAM and its pathway genes influence susceptibility to reporting musculoskeletal pain in the population.

Re: Frailty and sexual health in older European men

PURPOSE The use of anabolic androgenic steroids has not been traditionally discussed in mainstream medicine. With the increased diagnosis of hypogonadism a heterogeneous population of men is now being evaluated. In this larger patient population the existence of anabolic steroid induced hypogonadism, whether transient or permanent, should now be considered. MATERIALS AND METHODS We performed an initial retrospective database analysis of all 6,033 patients who sought treatment for hypogonadism from 2005 to 2010. An anonymous survey was subsequently distributed in 2012 to established patients undergoing testosterone replacement therapy. RESULTS Profound hypogonadism, defined as testosterone 50 ng/dl or less, was identified in 97 men (1.6%) in the large retrospective cohort initially reviewed. The most common etiology was prior anabolic androgenic steroid exposure, which was identified in 42 men (43%). Because of this surprising data, we performed an anonymous followup survey of our current hypogonadal population of 382 men with a mean±SD age of 49.2±13.0 years. This identified 80 patients (20.9%) with a mean age of 40.4±8.4 years who had prior anabolic androgenic steroid exposure. Hypogonadal men younger than 50 years were greater than 10 times more likely to have prior anabolic androgenic steroid exposure than men older than 50 years (OR 10.16, 95% CI 4.90-21.08). Prior anabolic androgenic steroid use significantly correlated negatively with education level (ρ=-0.160, p=0.002) and number of children (ρ=-0.281, p<0.0001). CONCLUSIONS Prior anabolic androgenic steroid use is common in young men who seek treatment for symptomatic hypogonadism and anabolic steroid induced hypogonadism is the most common etiology of profound hypogonadism. These findings suggest that it is necessary to refocus the approach to evaluation and treatment paradigms in young hypogonadal men.