T h e ne w e ngl a nd jou r na l o f m e dic i ne n engl j med 363;2 nejm

Complex multiple alterations in the hypothalamic-pituitary-testicular axis function exist in aging men against a background of progressive age-related testicular impairment. These changes are differentially linked to specific risk factors. Some risk factors operate independently of but others interact with age, in contributing to the T decline. These potentially modifiable risk factors suggest possible preventative measures to maintain T during aging in men.

Symptomatic elderly men considered to have LOH can be differentiated on the basis of endocrine and clinical features and predisposing risk factors. Secondary hypogonadism is associated with obesity and primary hypogonadism predominately with age. Compensated hypogonadism can be considered a distinct clinical state associated with aging. Classification of LOH into different categories by combining LH with T may improve the diagnosis and management of LOH.

BackgroundBefore considering whether to use a multivariable (diagnostic or prognostic) prediction model, it is essential that its performance be evaluated in data that were not used to develop the model (referred to as external validation). We critically appraised the methodological conduct and reporting of external validation studies of multivariable prediction models.MethodsWe conducted a systematic review of articles describing some form of external validation of one or more multivariable prediction models indexed in PubMed core clinical journals published in 2010. Study data were extracted in duplicate on design, sample size, handling of missing data, reference to the original study developing the prediction models and predictive performance measures.Results11,826 articles were identified and 78 were included for full review, which described the evaluation of 120 prediction models. in participant data that were not used to develop the model. Thirty-three articles described both the development of a prediction model and an evaluation of its performance on a separate dataset, and 45 articles described only the evaluation of an existing published prediction model on another dataset. Fifty-seven percent of the prediction models were presented and evaluated as simplified scoring systems. Sixteen percent of articles failed to report the number of outcome events in the validation datasets. Fifty-four percent of studies made no explicit mention of missing data. Sixty-seven percent did not report evaluating model calibration whilst most studies evaluated model discrimination. It was often unclear whether the reported performance measures were for the full regression model or for the simplified models.ConclusionsThe vast majority of studies describing some form of external validation of a multivariable prediction model were poorly reported with key details frequently not presented. The validation studies were characterised by poor design, inappropriate handling and acknowledgement of missing data and one of the most key performance measures of prediction models i.e. calibration often omitted from the publication. It may therefore not be surprising that an overwhelming majority of developed prediction models are not used in practice, when there is a dearth of well-conducted and clearly reported (external validation) studies describing their performance on independent participant data.

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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 (GS.D.) 4.4G0.3 years later. Results: Paired testosterone results were available for 2395 men. Mean (GS.D.) annualised hormone changes were as follows: testosterone K0.1G0.95 nmol/l; free testosterone (FT) K3.83 G16.8 pmol/l; sex hormone-binding globulin (SHBG) 0.56G2.5 nmol/l and LH 0.08G0.57 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 R15% 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.

Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials.

Our population is ageing, and obesity is increasing in the elderly bringing massive and rapidly changing burdens of ill health related to increased body weights and fat as well as the main drivers of poor diet and inactivity. Overweight and obesity, and a static body mass index (BMI) commonly conceal sarcopenia (gain in body fat but loss of muscle mass and functional capacity) in older people, aggravated by inactivity. A systematic computerized literature search using an iterative manipulation process of the keywords: obesity, elderly, weight loss. The following databases were accessed on 20 October 2010: Medline, Cochrane Collaboration, Ovid and Scholar Google. A large number of clinical consequences of overweight and obesity are particularly problematic for elderly individuals, including type 2 diabetes mellitus, arthritis, urinary incontinence and depression. The observation that the BMI value associated with the lowest relative mortality is slightly higher in older than in younger adults has often been misinterpreted that obesity is not as harmful in the elderly. BMI may be a less appropriate index in the elderly. All the medical consequences of obesity are multi-factorial but all are alleviated by modest, achievable weight loss (5-10 kg) with an evidence-based maintenance strategy. Since sarcopenic obesity is common in the elderly, a combination of exercise and modest calorie restriction appears to be the optimal method of reducing fat mass and preserving muscle mass. Reduction in polypharmacy is a valuable target for weight management. Age is not an obstacle to weight management interventions using moderate calorie restriction and exercise, and the currently licensed drug orlistat appears to have no age-related hazards. Overall balance of clinical outcomes has not been evaluated. In older people the risks from bariatric surgery outweigh benefits. Obesity, and specifically sarcopenic obesity, should also be prevented not only from younger age, but also during major life transitions including retirement, to improve better health outcomes and quality of life in later years, with a focus on those in 'obese families', where the main increases in obesity are located. Randomized controlled trials to determine health benefits and risks from long-term weight management in obese elderly are necessary.