Insulin-like peptide 3 (INSL3) as an indicator of leydig cell insufficiency (LCI) in Middle-aged and older men with hypogonadism: reference range and threshold.

Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential primary hypogonadism. Using results from large cohort studies we explore sources of biological and technical variance, and establish a reference range for adult men. It is constitutively secreted with little within-individual variation and reflects testicular capacity to produce testosterone.

Does testosterone influence the association between sleep and frailty in men: results from the European Male Aging Study.

Background: Previous studies have suggested an association between sleep disturbance and frailty. The mechanism is unknown, although it has been suggested that hormonal factors may play a role.

Methods: The aim was to determine the association between sleep duration, sleep quality and frailty, and to determine whether testosterone influenced this association.

Reproductive hormone levels, androgen receptor CAG repeat length and their longitudinal relationships with decline in cognitive subdomains in men: The European Male Ageing Study.

Objective: It has been proposed that endogenous sex hormone levels may present a modifiable risk factor for cognitive decline. However, the evidence for effects of sex steroids on cognitive ageing is conflicting. We therefore investigated associations between endogenous hormone levels, androgen receptor CAG repeat length, and cognitive domains including visuoconstructional abilities, visual memory, and processing speed in a large-scale longitudinal study of middle-aged and older men.

European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: Endorsing organization: European Society of Endocrinology.

Background: Evidence regarding functional hypogonadism, previously referred to as 'late-onset' hypogonadism, has increased substantially during the last 10 year.

Objective: To update the European Academy of Andrology (EAA) guidelines on functional hypogonadism.

Methods: Expert group of academicians appointed by the EAA generated a series of consensus recommendations according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system.

Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.

Objective: To update the "Testosterone Therapy in Men With Androgen Deficiency Syndromes" guideline published in 2010.

Participants: The participants include an Endocrine Society-appointed task force of 10 medical content experts and a clinical practice guideline methodologist.

Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence.

Ethnic differences in male reproductive hormones and relationships with adiposity and insulin resistance in older men.

Objectives: To assess ethnic differences in male reproductive hormone levels and to determine whether any differences are explained by adiposity, insulin resistance (IR) or comorbidities in older men.

Design: Multi-ethnic cross-sectional observational study.

Participants: Community dwelling middle-aged and elderly men residing in the UK aged 40-84 years of South Asian (SA; n = 180), White European (WE; n = 328) or African Caribbean (AC; n = 166) origin.

Frailty and bone health in European men.

Background: frailty is associated with an increased risk of fragility fractures. Less is known, however, about the association between frailty and bone health.

Methods: men aged 40-79 years were recruited from population registers in eight European centres for participation in the European Male Aging Study.

Does Pain Predict Frailty in Older Men and Women? Findings From the English Longitudinal Study of Ageing (ELSA).

Background: Pain has been suggested to act as a stressor during aging, potentially accelerating declines in health and functioning. Our objective was to examine the longitudinal association between self-reported pain and the development, or worsening, of frailty among older men and women.

Methods: The study population consisted of 5,316 men and women living in private households in England, mean age 64.

Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men.

Context: The development of a safe and effective reversible method of male contraception is still an unmet need.

Objective: Evaluation of suppression of spermatogenesis and contraceptive protection by coadministered im injections of progestogen and testosterone.

Design: Prospective multicentre study.

Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME).

Aims: The aim of this study was to assess cardiovascular (CV) safety of testosterone replacement therapy (TRT) in a large, diverse cohort of European men with hypogonadism (HG).

Methods: The Registry of Hypogonadism in Men (RHYME) was designed as a multi-national, longitudinal disease registry of men diagnosed with hypogonadism (HG) at 25 clinical sites in six European countries. Data collection included a complete medical history, physical examination, blood sampling and patient questionnaires at multiple study visits over 2-3 years.

Changes in prevalence of obesity and high waist circumference over four years across European regions: the European male ageing study (EMAS).

Diversity in lifestyles and socioeconomic status among European populations, and recent socio-political and economic changes in transitional countries, may affect changes in adiposity. We aimed to determine whether change in the prevalence of obesity varies between the socio-politically transitional North-East European (Łódź, Poland; Szeged, Hungary; Tartu, Estonia), and the non-transitional Mediterranean (Santiago de Compostela, Spain; Florence, Italy) and North-West European (Leuven, Belgium; Malmö, Sweden; Manchester, UK) cities. This prospective observational cohort survey was performed between 2003 and 2005 at baseline and followed up between 2008 and 2010 of 3369 community-dwelling men aged 40-79 years.

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.

Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men.

Objectives: To evaluate the effects of testosterone-replacement therapy (TRT) on prostate health indicators in hypogonadal men, including rates of prostate cancer diagnoses, changes in prostate-specific antigen (PSA) levels and lower urinary tract symptoms (LUTS) over time.

Patients And Methods: The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry of treated and untreated, newly-diagnosed hypogonadal men (n = 999). Follow-up assessments were performed at 3-6, 12, 24, and 36 months.

Natural history, risk factors and clinical features of primary hypogonadism in ageing men: Longitudinal Data from the European Male Ageing Study.

Objective: In ageing men, the incidence and clinical significance of testosterone (T) decline accompanied by elevated luteinizing hormone (LH) are unclear. We describe the natural history, risk factors and clinical features associated with the development of biochemical primary hypogonadism (PHG, T < 10·5 nmol/l and LH>9·4U/l) in ageing men.

Design, Patients And Measurements: A prospective observational cohort survey of 3,369 community-dwelling men aged 40-79 years, followed up for 4·3 years.

A frailty index based on laboratory deficits in community-dwelling men predicted their risk of adverse health outcomes.

Background: abnormal laboratory test results accumulate with age and can be common in people with few clinically detectable health deficits. A frailty index (FI) based entirely on common physiological and laboratory tests (FI-Lab) might offer pragmatic and scientific advantages compared with a clinical FI (FI-Clin).

Objectives: to compare the FI-Lab with the FI-Clin and to assess their individual and combined relationships with mortality and other adverse health outcomes.

Interactions Between Depression and Lower Urinary Tract Symptoms: The Role of Adverse Life Events and Inflammatory Mechanisms. Results From the European Male Ageing Study.

Objectives: Depression and lower urinary tract symptoms (LUTSs) have been found to co-occur among aging men. The present study attempted to clarify the nature of this relationship, considering adverse life events as potential moderators and the inflammation as an underlying biological mechanism.

Methods: The relationship between depression and LUTS was evaluated using data from the European Male Ageing Study, the largest multicenter population-based study of aging in European men.

Low Free Testosterone Is Associated with Hypogonadal Signs and Symptoms in Men with Normal Total Testosterone.

Context: During aging, total testosterone (TT) declines and SHBG increases, resulting in a greater decrease in calculated free T (cFT). Currently, guidelines suggest using TT to diagnose androgen deficiency and to reserve cFT only for men with borderline TT.

Objective: Our objective was to investigate if either low cFT or low TT is more strongly associated with androgen-related clinical endpoints.

Low vitamin D and the risk of developing chronic widespread pain: results from the European male ageing study.

Background: The association between low levels of vitamin D and the occurrence of chronic widespread pain (CWP) remains unclear. The aim of our analysis was to determine the relationship between low vitamin D levels and the risk of developing CWP in a population sample of middle age and elderly men.

Methods: Three thousand three hundred sixty nine men aged 40-79 were recruited from 8 European centres for a longitudinal study of male ageing, the European Male Ageing Study.

Chronic widespread pain is associated with worsening frailty in European men.

Background: we hypothesised that chronic widespread pain (CWP), by acting as a potential stressor, may predispose to the development of, or worsening, frailty.

Setting: longitudinal analysis within the European Male Ageing Study (EMAS).

Participants: a total of 2,736 community-dwelling men aged 40-79.

A direct assay for the routine measurement of testosterone, androstenedione, dihydrotestosterone and dehydroepiandrosterone by liquid chromatography tandem mass spectrometry.

Background: The measurement of androgens in many laboratories is often limited to testosterone. To more accurately determine the androgen status in both sexes, the measurement of other androgens such as dihydrotestosterone, the more potent metabolite of testosterone, and androstenendione and dehydroepiandrosterone, the most abundant circulating androgens in women would be informative. We report a combined liquid chromatography tandem mass spectrometry method for the measurement of these androgens.

Socioeconomic conditions across life related to multiple measures of the endocrine system in older adults: Longitudinal findings from a British birth cohort study.

Background: Little is known about how socioeconomic position (SEP) across life impacts on different axes of the endocrine system which are thought to underlie the ageing process and its adverse consequences. We examined how indicators of SEP across life related to multiple markers of the endocrine system in late midlife, and hypothesized that lower SEP across life would be associated with an adverse hormone profile across multiple axes.

Methods: Data were from a British cohort study of 875 men and 905 women followed since their birth in March 1946 with circulating free testosterone and insulin-like growth factor-I (IGF-I) measured at both 53 and 60-64 years, and evening cortisol at 60-64 years.

Endocrine determinants of incident sarcopenia in middle-aged and elderly European men.

Background: In men, the long-term consequences of low serum levels of sex steroids, vitamin D metabolites, and insulin-like growth factor 1 (IGF-1) on the evolution of muscle mass, muscle strength, or physical performance are unclear. Moreover, there are no data about the relationship between these hormones and incident sarcopenia defined as low muscle mass and function. The aim of this study was to determine whether the baseline levels of sex hormones, vitamin D metabolites, and IGF-1 predict changes in muscle mass, muscle strength, physical performance, and incident sarcopenia.

Low heel ultrasound parameters predict mortality in men: results from the European Male Ageing Study (EMAS).

Background: low bone mineral density measured by dual-energy x-ray absorptiometry is associated with increased mortality. The relationship between other skeletal phenotypes and mortality is unclear. The aim of this study was to determine the relationship between quantitative heel ultrasound parameters and mortality in a cohort of European men.

Changes in testosterone related to body composition in late midlife: Findings from the 1946 British birth cohort study.

Objective: Randomized trials in men with testosterone deficiency have provided evidence of short-term effects of testosterone therapy on muscle and fat mass but it is unclear whether this persists over a longer period or how testosterone affects women. We examined whether the midlife decline in testosterone relates to fat and lean mass in both sexes.

Methods: Data were collected from 440 men and 560 women participating in the 1946 British birth cohort study with testosterone measured at 53 and/or 60-64 years.