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Non‐surgical (reversible) male contraception methods, when approved for general clinical application, should be made available to all interested men aged 18 50 years in good general health regardless of their semen parameters. In the preliminary workup, a complete personal and family history aimed at identifying specific conditions that may potentially increase the risks for adverse effects (associated with testosterone replacement) is advisable but a general or andrological examination is not required, unless indicated by the history. Baseline body weight, blood pressure and haemoglobin should be recorded for the purpose of future monitoring. While risks and benefits of vasectomy have been well established, appropriately nuanced patient counselling and assessment are essential for ensuring a satisfactory outcome of vasectomy. [ABSTRACT FROM AUTHOR]

Backgrounds: Despite a wide spectrum of contraceptive methods for women, the unintended pregnancy rate remains high (45% in the US), with 50% resulting in abortion. Currently, 20% of global contraceptive use is male‐directed, with a wide variation among countries due to limited availability and lack of efficacy. Worldwide studies indicate that >50% of men would opt to use a reversible method, and 90% of women would rely on their partner to use a contraceptive. Additional reasons for novel male contraceptive methods to be available include the increased life expectancy, sharing the reproductive risks among partners, social issues, the lack of pharma industry involvement and the lack of opinion makers advocating for male contraception. Aim: The present guidelines aim to review the status regarding male contraception, the current state of the art to support the clinical practice, recommend minimal requirements for new male contraceptive development and provide and grade updated, evidence‐based recommendations from the European Society of Andrology (EAA) and the American Society of Andrology (ASA). Methods: An expert panel of academicians appointed by the EAA and the ASA generated a consensus guideline according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. Results: Sixty evidence‐based and graded recommendations were produced on couple‐centered communication, behaviors, barrier methods, semen analysis and contraceptive efficacy, physical agents, surgical methods, actions before initiating male contraception, hormonal methods, non‐hormonal methods, vaccines, and social and ethical considerations. Conclusion: As gender roles transform and gender equity is established in relationships, the male contribution to family planning must be facilitated. Efficient and safe male‐directed methods must be evaluated and introduced into clinical practice, preferably reversible, either hormonal or non‐hormonal. From a future perspective, identifying new hormonal combinations, suitable testicular targets, and emerging vas occlusion methods will produce novel molecules and products for male contraception. [ABSTRACT FROM AUTHOR]

Objective: Older men on an average have lower testosterone concentrations, compared with younger men, and more age-related comorbidities. Whether lower testosterone concentrations contribute to biological ageing remains unclear. Shorter telomeres are a marker for biological age. We tested the hypothesis that testosterone concentrations are associated with leucocyte telomere length (LTL), in middle- to older-aged men. Design: Cross-sectional analysis of the UK Biobank study, involving community-dwelling men aged 40-69 years. Methods: Serum testosterone and sex hormone-binding globulin (SHBG) were assayed. Free testosterone was calculated (cFT). Leucocyte telomere length was measured using polymerase chain reaction. Multivariable models were used to assess associations of hormones with standardised LTL. Results: In 167 706 men, median age 58 years, adjusting for sociodemographic, lifestyle, and medical factors, total testosterone was inversely associated with standardised LTL, which was 0.09 longer (95% confidence interval [CI], 0.08-0.10, P < .001) in men with total testosterone at median of lowest quintile [Q1] vs highest [Q5]. This relationship was attenuated after additional adjustment for SHBG (0.03 longer, CI = 0.02-0.05, P = .003). The association between cFT and LTL was similar in direction but lower in magnitude. In multivariable analysis, SHBG was inversely associated with standardised LTL, which was 0.12 longer (CI = 0.10-0.13, P < .001) for SHBG at median Q1 vs Q5. Results were similar with testosterone included in the model (0.10 longer, CI = 0.08-0.12, P < .001). Conclusions: Total testosterone and SHBG were independently and inversely associated with LTL. Men with higher testosterone or SHBG had shorter telomeres, arguing against a role for testosterone to slow biological ageing in men. [ABSTRACT FROM AUTHOR]

Background: Insulin-like peptide 3 (INSL3) is a constitutive hormone secreted in men by the mature Leydig cells of the testes. It is an accurate biomarker for Leydig cell functional capacity, reflecting their total cell number and differentiation status. Objectives: To determine the ability of INSL3 to predict hypogonadismand agerelated morbidity using the EMAS cohort of older community-dwelling men. Materials & methods: Circulating INSL3 was assessed in the EMAS cohort and its cross-sectional and longitudinal relationships to hypogonadism, here defined by testosterone (T) <10.5nmol/l, and a range of age-related morbidities determined by correlation and regression analysis. Results & discussion: While INSL3 is an accurate measure of primary hypogonadism, secondary and compensated hypogonadism also indicate reduced levels of INSL3, implying that testicular hypogonadism does not improve even when LH levels are increased, and that ageing-related hypogonadism may combine both primary and secondary features. Unadjusted, serum INSL3, like calculated free testosterone (cFT), LH, or the T/LH ratio reflects hypogonadal status and is associated with reduced sexual function, bone mineral density, and physical activity, as well as increased occurrence of hypertension, cardiovascular disease, cancer, and diabetes. Using multiple regression analysis to adjust for a range of hormonal, anthropometric, and lifestyle factors, this relationship is lost for all morbidities, except for reduced bone mineral density, implying that INSL3 and/or its specific receptor, RXFP2, may be causally involved in promoting healthy bone metabolism. Elevated INSL3 also associates with hypertension and cardiovascular disease. When unadjusted, INSL3 in phase 1 of the EMAS study was assessed for its association with morbidity in phase 2 (mean 4.3 years later); INSL3 significantly predicts 7 out of 9 morbidity categories, behaving as well as cFT in this regard. In contrast, total T was predictive in only 3 of the 9 categories. Conclusion: Together with its low within-individual variance, these findings suggest that assessing INSL3 in men could offer important insight into the later development of disease in the elderly. [ABSTRACT FROM AUTHOR]

Background: Aging in men is accompanied by a broad range of symptoms, including sexual dysfunction, cognitive and musculoskeletal decline, obesity, type 2 diabetes, cardiovascular disease and hypertension, organ degeneration/failure, and increasing neoplasia, some of which are associated with declining levels of Leydig cell‐produced testosterone. High natural biological variance, together with multiple factors that can modulate circulating testosterone concentration, may influence its interpretation and clinical implications. Insulin‐like peptide 3 is a biomarker of Leydig cell function that might provide complementary information on testicular health and its downstream outcomes. Objectives: To characterize insulin‐like peptide 3 as a biomarker to assess gonadal status in aging men. Methods and materials: A large European multicenter (European Male Aging Study) cohort of community‐dwelling men was analyzed to determine how insulin‐like peptide 3 relates to a range of hormonal, anthropometric, and lifestyle parameters. Results and discussion: Insulin‐like peptide 3 declines cross‐sectionally and longitudinally within individuals at approximately 15% per decade from age 40 years, unlike testosterone (1.9% per decade), which is partly compensated by increasing pituitary luteinizing hormone production. Importantly, lower insulin‐like peptide 3 in younger men appears to persist with aging. Multiple regression analysis shows that, unlike testosterone, insulin‐like peptide 3 is negatively dependent on luteinizing hormone and sex hormone‐binding globulin and positively dependent on follicle‐stimulating hormone, suggesting a different mechanism of gonadotropic regulation. Circulating insulin‐like peptide 3 is negatively associated with increased body mass index or waist circumference and with smoking, and unlike testosterone, it is not affected by weight loss in obese individuals. Geographic variation in mean insulin‐like peptide 3 within Europe appears to be largely explained by differences in these parameters. The results allowed the establishment of a European‐wide reference range for insulin‐like peptide 3 (95% confidence interval) adjusted for increasing age. Conclusion: Insulin‐like peptide 3 is a constitutive biomarker of Leydig cell functional capacity and is a robust, reliably measurable peptide not subject to gonadotropin‐dependent short‐term regulation and within‐individual variation in testosterone. [ABSTRACT FROM AUTHOR]

Objective: Men are at greater risk from COVID-19 than women. Older, overweight men, and those with type 2 diabetes, have lower testosterone concentrations and poorer COVID-19-related outcomes. We analysed the associations of premorbid serum testosterone concentrations, not confounded by the effects of acute SARS-CoV-2 infection, with COVID-19-related mortality risk in men. Design: This study is a United Kingdom Biobank prospective cohort study of community-dwelling men aged 40-69 years. Methods: Serum total testosterone and sex hormone-binding globulin (SHBG) were measured at baseline (2006-2010). Free testosterone values were calculated (cFT). the incidence of SARS-CoV-2 infections and deaths related to COVID-19 were ascertained from 16 March 2020 to 31 January 2021 and mode lled using time-stratified Cox regression. Results: In 159 964 men, there were 5558 SARS-CoV-2 infections and 438 COVID-19 deaths. Younger age, higher BMI, non-White ethnicity, lower educational attainment, and socioeconomic deprivation were associated with incidence of SARS-CoV-2 infections but total testosterone, SHBG, and cFT were not. Adjusting for potential confounders, higher total testosterone was associated with COVID-19-related mortality risk (overall trend P = 0.008; hazard ratios (95% CIs) quintile 1, Q1 vs Q5 (reference), 0.84 (0.65-1.12) Q2:Q5, 0.82 (0.63-1.10); Q3:Q5, 0.80 (0.66-1.00); Q4:Q5, 0.82 (0.75-0.93)). Higher SHBG was also associated with COVID-19 mortality risk (P = 0.008), but cFT was not (P = 0.248). Conclusions: Middle-aged to older men with the highest premorbid serum total testosterone and SHBG concentrations are at greater risk of COVID-19-related mortality. Men could be advised that having relatively high serum testosterone concentrations does not protect against future COVID-19-related mortality. Further investigation of causality and potential underlying mechanisms is warranted. [ABSTRACT FROM AUTHOR]

Background erectile dysfunction is associated with mortality, whereas the association between low testosterone (T) and higher mortality remains controversial. Sexual dysfunction and low T often coexist, but the relative importance of sexual symptoms versus low T in predicting mortality is not known. We studied the interrelationships between sex steroids and sexual symptoms with all-cause mortality in a large prospective cohort of European men. Design survival status was assessed in 1,788 community-dwelling men, aged 40–79, who participated in the European Male Ageing Study (EMAS). Sexual symptoms were evaluated via a validated questionnaire (EMAS-SFQ). Sex steroids were measured by mass spectrometry. Cox proportional hazard models were used to study the association between hormones, sexual symptoms and mortality. Results about 420 (25.3%) men died during a mean follow-up of 12.6 ± 3.1 years. Total T levels were similar in both groups, but free T was lower in those who died. Men with three sexual symptoms (erectile dysfunction, reduced morning erections and lower libido) had a higher mortality risk compared with men with none of these symptoms (adjusted hazard ratio (HR) and 95% confidence intervals: 1.75 (1.28–2.40, P  = 0.001)). Particularly, erectile dysfunction and poor morning erections, but not lower libido, were associated with increased mortality (HR 1.40 (1.13–1.74, P  = 0.002), 1.28 (1.04–1.59, P  = 0.023) and 1.12 (0.90–1.39, P  = 0.312), respectively). Further adjusting for total T, free T or oestradiol did not influence the observed risk. Conclusions sexual symptoms, in particular erectile dysfunction, predict all-cause mortality independently of sex steroids and can be an early warning sign of a poor health status. [ABSTRACT FROM AUTHOR]

Summary: Objective: Testosterone and sex hormone‐binding globulin (SHBG) concentrations are reported to decline during male ageing, but whether these changes reflect physiological ageing or age‐related comorbidities remains uncertain. We examined longitudinal changes in serum testosterone and SHBG concentrations in middle‐aged to older men, concordance between baseline and follow‐up values and relationships with concomitant changes in lifestyle and medical factors. Design: Population‐based longitudinal cohort study. Participants: Community‐dwelling men aged 40–69 years. Measurements: Immunoassay serum total testosterone (n = 7812) and SHBG (n = 6491) at baseline (2006–2010) and follow‐up (2012–2013). Free testosterone (cFT) was calculated. Bland–Altman analyses and concordance correlation of repeated measurements were conducted. Associations of changes in hormone concentrations with lifestyle and medical factors were explored using Spearman's rank correlation. Results: Over 4.3 years follow‐up, there was a negligible mean change (±SE) in serum total testosterone concentration (+0.06 ± 0.03 nmol/L), whereas mean SHBG concentration increased (+3.69 ± 0.12 nmol/L) and cFT decreased (−10.7 ± 0.7 pmol/L). Concordance estimates were 0.67 (95% confidence interval [CI]: 0.66–0.69) for total testosterone, 0.83 (CI = 0.82–0.84) for SHBG and 0.56 (CI = 0.54–0.58) for cFT. Changes in serum total testosterone correlated with changes in SHBG (Spearman's rank ρ = 0.33, CI = 0.30–0.35), and inversely with changes in body mass index (BMI) (ρ = −0.18, CI = −0.20 to −0.16) and waist circumference (ρ = −0.13, CI = −0.15 to −0.11) and in SHBG with changes in BMI (ρ = −0.34, CI = −0.36 to −0.32) and waist circumference (ρ = −0.21, CI = −0.24 to −0.19). Conclusion: In relatively healthy middle‐aged to older men, mean serum total testosterone concentration is stable with ageing, while mean SHBG concentration increases. Both total testosterone and SHBG concentrations were highly concordant over time. [ABSTRACT FROM AUTHOR]

Context: Low total 25-hydroxyvitamin D (25(OH)D) has been associated with mortality. Whether vitamin D in its free form or 1,25-dihydroxyvitamin D (1,25(OH)2D), provide any additional information is unclear. Objective: To determine what level of 25(OH)D is predictive for mortality and if free 25(OH)D or 1,25(OH) 2 D concentrations have any added value. Methods: This prospective cohort comprised 1915 community-dwelling men, aged 40 to 79 years. Intervention included determination of association of total and free 25(OH)D and 1,25(OH) 2 D concentrations with survival status. Vitamin D results were grouped into quintiles. For total 25(OH)D, specific cutoff values were also applied. Cox proportional hazard models were used adjusted for center, body mass index, smoking, alcohol, physical activity, season of blood sample, kidney function, and number of comorbidities. Results: A total of 469 (23.5%) men died during a mean follow-up of 12.3 ± 3.4 years. Compared to those with normal vitamin D values (> 30 µg/L), men with a total 25(OH)D of less than 20 µg/L had an increased mortality (hazard ratio [HR] 2.03 [95% CI, 1.39-2.96]; P < .001). Likewise, men in the lowest 3 free 25(OH)D quintiles (< 4.43 ng/L) had a higher mortality risk compared to the highest quintile (HR 2.09 [95% CI, 1.34-3.25]; P < .01). Mortality risks were similar across all 1,25(OH)2D and vitamin D binding protein quintiles. Conclusion: Aging men with vitamin D deficiency have a 2-fold increased mortality risk. Determinations of either the free fractions of vitamin D or measurement of its active form offer no additional information on mortality risks. [ABSTRACT FROM AUTHOR]

Male hypogonadism (MH) is a common endocrine disorder. However, uncertainties and variations in its diagnosis and management exist. There are several current guidelines on testosterone replacement therapy that have been driven predominantly by single disciplines. The Society for Endocrinology commissioned this new guideline to provide all care providers with a multidisciplinary approach to treating patients with MH. This guideline has been compiled using expertise from endocrine (medical and nursing), primary care, clinical biochemistry, urology and reproductive medicine practices. These guidelines also provide a patient perspective to help clinicians best manage MH. [ABSTRACT FROM AUTHOR]

Objective: Serum testosterone concentrations are affected by factors unrelated to hypothalamo‐pituitary‐testicular axis pathology. We evaluated the impact of sociodemographic, lifestyle and medical factors, on serum testosterone and sex hormone–binding globulin (SHBG) in men aged 40‐69 years. Design: Cross‐sectional analysis of 208,677 community‐dwelling men from the UK Biobank. Measurements: We analysed associations of different factors with serum testosterone and SHBG (immunoassays) and calculated free testosterone (cFT), using smoothed centile plots, linear mixed models and effect size estimates. Results: Median (interquartile range) for serum testosterone was 11.6 (9.4‐14.1) nmol/L, SHBG 36.9 (27.9‐48.1) nmol/L and cFT 213 (178‐255) pmol/L. Age and BMI were inversely associated with testosterone and cFT, while SHBG was associated with age and inversely with BMI (all P <.001). Living with a partner, (South) Asian ethnicity, never or previous smoker and some medical conditions were associated with lower testosterone. Poultry or fish eater, and higher physical activity were associated with higher testosterone (all P <.001). Testosterone was lowered by ~0.5 nmol/L across ages, ~1.5 nmol/L for BMI 30 vs 25 kg/m2, ~2 nmol/L for (South) Asian ethnicity, living with partner, college/university qualifications, low red meat eater, insufficient physical activity and 0.3‐1.0 nmol/L with cardiovascular disease or diabetes. Different combinations of these factors varied serum testosterone by ~4 nmol/L, SHBG by ~30 nmol/L and cFT by ~60 pmol/L. Conclusions: The identified modifiable risk factors support lifestyle‐based interventions in men with low testosterone concentrations. Considering sociodemographic, lifestyle and medical factors facilitates more personalized interpretation of testosterone testing results with respect to existing reference ranges. [ABSTRACT FROM AUTHOR]

Summary: Objective: The purpose of this narrative review was to summarize available data on testosterone levels in normal, healthy adult males and females, to provide a physiologic reference framework to evaluate testosterone levels reported in males and females with conditions that elevate androgens, such as disorders of sex development (DSD), and to determine the separation or overlap of testosterone levels between normal and affected males and females. Methods: A literature review was conducted for published papers, from peer reviewed journals, reporting testosterone levels in healthy males and females, males with 46XY DSD, and females with hyperandrogenism due to polycystic ovary syndrome (PCOS). Papers were selected that had adequate characterization of participants, and description of the methodology for measurement of serum testosterone and reporting of results. Results: In the healthy, normal males and females, there was a clear bimodal distribution of testosterone levels, with the lower end of the male range being four‐ to fivefold higher than the upper end of the female range(males 8.8‐30.9 nmol/L, females 0.4‐2.0 nmol/L). Individuals with 46XY DSD, specifically those with 5‐alpha reductase deficiency, type 2 and androgen insensitivity syndrome testosterone levels that were within normal male range. Females with PCOS or congenital adrenal hyperplasia were above the normal female range but still below the normal male range. Conclusions: Existing studies strongly support a bimodal distribution of serum testosterone levels in females compared to males. These data should be considered in the discussion of female competition eligibility in individuals with possible DSD or hyperandrogenism. [ABSTRACT FROM AUTHOR]

Summary: Objective: Limited evidence supports the use of free testosterone (FT) for diagnosing hypogonadism when sex hormone–binding globulin (SHBG) is altered. Low total testosterone (TT) is commonly encountered in obesity where SHBG is typically decreased. We aimed to assess the contribution of FT in improving the diagnosis of symptomatic secondary hypogonadism (SH), identified initially by low total testosterone (TT), and then further differentiated by normal FT (LNSH) or low FT (LLSH). Design: Prospective observational study with a median follow‐up of 4.3 years. Patients: Three thousand three hundred sixty‐nine community‐dwelling men aged 40‐79 years from eight European centres. Measurements: Subjects were categorized according to baseline and follow‐up biochemical status into persistent eugonadal (referent group; n = 1880), incident LNSH (eugonadism to LNSH; n = 101) and incident LLSH (eugonadism to LLSH; n = 38). Predictors and clinical features associated with the transition from eugonadism to LNSH or LLSH were assessed. Results: The cumulative incidence of LNSH and LLSH over 4.3 years was 4.9% and 1.9%, respectively. Baseline obesity predicted both LNSH and LLSH, but the former occurred more frequently in younger men. LLSH, but not LNSH, was associated with new/worsened sexual symptoms, including low desire [OR = 2.67 (1.27‐5.60)], erectile dysfunction [OR = 4.53 (2.05‐10.01)] and infrequent morning erections [OR = 3.40 (1.48‐7.84)]. Conclusions: These longitudinal data demonstrate the importance of FT in the diagnosis of hypogonadism in obese men with low TT and SHBG. The concurrent fall in TT and FT identifies the minority (27.3%) of men with hypogonadal symptoms, which were not present in the majority developing low TT with normal FT. [ABSTRACT FROM AUTHOR]

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 64.5 years, participating in the English Longitudinal Study of Ageing (ELSA). Data from Waves 2 and 6 of ELSA were used in this study with 8 years of follow-up. At Wave 2, participants were asked whether they were "often troubled with pain" and for those who reported yes, further information regarding the intensity of their pain (mild, moderate, or severe) was collected. Socioeconomic status (SES) was assessed using information about the current/most recent occupation and also net wealth. A frailty index (FI) was generated, with the presence of frailty defined as an FI >0.35. Among those without frailty at Wave 2, the association between pain at Wave 2 and frailty at Wave 6 was examined using logistic regression. We investigated whether pain predicted change in FI between Waves 2 and 6 using a negative binomial regression model. For both models adjustments were made for age, gender, lifestyle factors, depressive symptoms, and socioeconomic factors.Results: At Wave 2, 455 (19.7%) men and 856 (28.7%) women reported they often experienced moderate or severe pain. Of the 5,159 participants who were nonfrail at Wave 2, 328 (6.4%) were frail by Wave 6. The mean FI was 0.11 (standard deviation [SD] = 0.1) at Wave 2 and 0.15 (SD = 0.1) at Wave 6. After adjustment for age, gender, body mass index, lifestyle factors, and depressive symptoms, compared to participants reporting no pain at Wave 2 those reporting moderate (odds ratio [OR] = 3.08, 95% confidence interval [CI] = 2.28, 4.16) or severe pain (OR = 3.78, 95% CI = 2.51, 5.71) were significantly more likely to be frail at Wave 6. This association persisted after further adjustment for either occupational class and/or net wealth level. Compared to those without pain, those with mild, moderate, or severe pain were also more likely to develop worsening frailty, as assessed using the FI, and this association persisted after adjustment for SES. There was no evidence that the association between pain and frailty was influenced by gender.Conclusion: Pain is associated with an increased risk and intensity of frailty in older men and women. Socioeconomic factors contribute to the occurrence of frailty; though in our study do not explain the relationship between pain and frailty. [ABSTRACT FROM AUTHOR]

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. Design and subjects: secondary analysis of the eight-centre, longitudinal European Male Ageing Study (EMAS) of community-dwelling men aged 40-79 at baseline. Follow-up assessment occurred 4.4 ± 0.3 (mean ± SD) years later. Methods: we constructed a 23-item FI using common laboratory tests, blood pressure and pulse (FI-Lab), compared it with a previously validated 39-item FI using self-report and performance-based measures (FI-Clin) and finally combined both FIs to create a 62-item FI-Combined. Outcomes were all-cause mortality, institutionalisation, doctor visits, medication use, self-reported health, falls and fractures. Results: the mean FI-Lab score was 0.28 ± 0.11, the FI-Clin was 0.13 ± 0.11 and FI-Combined was 0.19 ± 0.09. Age-adjusted models demonstrated that each FI was associated with mortality [HR (CI) FI-Lab: 1.04 (1.03-1.06); FI-Clin: 1.05 (1.04-1.06); FI-Combined: 1.07 (1.06-1.09)], institutionalisation, doctor visits, medication use, self-reported health and falls. Combined in a model with FI-Clin, the FI-Lab remained independently associated with mortality, institutionalisation, doctor visits, medication use and self-reported health. Conclusions: the FI-Lab detected an increased risk of adverse health outcomes alone and in combination with a clinical FI; further evaluation of the feasibility of the FI-Lab as a frailty screening tool within hospital care settings is needed. [ABSTRACT FROM AUTHOR]

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. Methods: subjects completed a pain questionnaire and shaded a manikin, with the presence of CWP defined using the American College of Rheumatology criteria. Physical activity, smoking, alcohol consumption and depression were measured. Repeat assessments took place a median of 4.3 years later. A frailty index (FI) was used, with frail defined as an FI >0.35. The association between CWP at baseline and the new occurrence of frailty was examined using logistic regression; the association between CWP at baseline and change in FI was examined using negative binomial regression. Results: at baseline, 218 (8.3%) men reported CWP. Of the 2,631 men who were defined as non-frail at baseline, 112 (4.3%) were frail at follow-up; their mean FI was 0.12 (SD 0.1) at baseline and 0.15 (SD 0.1) at follow-up, with a mean change of 0.03 (SD 0.08) P ≤ 0.001. Among men who were non-frail at baseline, those with CWP were significantly more likely to develop frailty. After adjustment for age and centre, compared with those with no pain, those with CWP at baseline had a 70% higher FI at follow-up; these associations remained significant after further adjustment for smoking, body mass index, depression, physical activity and FI at baseline. Conclusion: the presence of CWP is associated with an increased risk of frailty in older European men. [ABSTRACT FROM AUTHOR]

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. Fat and appendicular lean mass were measured at 60-64 years using dual-energy X-ray absorptiometry. Results Mean free testosterone concentrations were lower at 60-64 than 53 years, by 26% in both sexes. At both ages testosterone was negatively associated with fat mass in men and positively associated in women. A larger decline in free testosterone was associated with higher fat mass in men but with lower fat mass among women. In contrast, declines in testosterone were not associated with lean mass in either sex. Conclusions Our findings suggest sex-divergent relationships between testosterone and fat mass and their distribution but do not support the hypothesis that midlife declines in testosterone lead to lower lean mass. [ABSTRACT FROM AUTHOR]

The fall in testosterone levels with age appears to be a real phenomenon. Declining testicular function and hypothalamic dysregulation appear to be the mechanisms explaining the fall in testosterone levels with age. The increased prevalence of obesity and chronic illness in ageing men both cause a large drop in testosterone levels independent of ageing. Age-related hypogonadism appears to be different to other ‘classical’ causes of hypogonadism. Testosterone levels are not unequivocally low and associated symptoms are non-specific. In frail older men with low testosterone levels, testosterone therapy appears to improve QOL and physical function. In less frail men, however, effects of testosterone therapy in the ageing male are small and/or inconsistent. There remains an urgent need for randomised clinical trials with sufficient size, duration and power to determine specific benefits and risks of testosterone therapy in older men. [ABSTRACT FROM AUTHOR]

The fall in testosterone levels with age appears to be a real phenomenon. Declining testicular function and hypothalamic dysregulation appear to be the mechanisms explaining the fall in testosterone levels with age. The increased prevalence of obesity and chronic illness in ageing men both cause a large drop in testosterone levels independent of ageing. Age-related hypogonadism appears to be different to other ‘classical’ causes of hypogonadism. Testosterone levels are not unequivocally low and associated symptoms are non-specific. In frail older men with low testosterone levels, testosterone therapy appears to improve QOL and physical function. In less frail men, however, effects of testosterone therapy in the ageing male are small and/or inconsistent. There remains an urgent need for randomised clinical trials with sufficient size, duration and power to determine specific benefits and risks of testosterone therapy in older men. [ABSTRACT FROM PUBLISHER]

Background: vitamin D deficiency has been associated with an increased risk of mortality, but whether this relationship is causal or linked to co-existent comorbidity and adverse life factors remains uncertain. Our objective was to determine whether endogenous 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) levels predicted all-cause, cardiovascular and cancer mortality independently of health and lifestyle factors.Setting: prospective cohort analysis within the European Male Ageing Study.Participants: 2,816 community-dwelling men aged 40–79 years at baseline.Methods: Cox regression was used to examine the association of all-cause mortality with 25(OH)D, 1,25(OH)2D and PTH; cardiovascular and cancer mortality were modelled using competing-risks regression. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CIs) for Cox models; sub-hazard ratios (SHR) and 95% CIs for competing-risks models.Results: a total of 187 men died during a median of 4.3 years of follow-up. Serum levels of 25(OH)D (per 1 SD decrease: HR = 1.45; 95% CI = 1.16, 1.81) and 1,25(OH)2D (per 1 SD decrease: HR = 1.20; 95% CI = 1.00, 1.44) were associated with an increased risk of all-cause mortality after adjusting for age, centre, smoking, self-reported morbidities, physical activity and functional performance. Only levels of 25(OH)D <25 nmol/l predicted cancer mortality (SHR = 3.33; 95% CI = 1.38, 8.04).Conclusion: lower 25(OH)D and 1,25(OH)2D levels independently predicted all-cause mortality in middle-aged and older European men. Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here. [ABSTRACT FROM AUTHOR]

Background: vitamin D deficiency has been associated with an increased risk of mortality, but whether this relationship is causal or linked to co-existent comorbidity and adverse life factors remains uncertain. Our objective was to determine whether endogenous 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) levels predicted all-cause, cardiovascular and cancer mortality independently of health and lifestyle factors.Setting: prospective cohort analysis within the European Male Ageing Study.Participants: 2,816 community-dwelling men aged 40–79 years at baseline.Methods: Cox regression was used to examine the association of all-cause mortality with 25(OH)D, 1,25(OH)2D and PTH; cardiovascular and cancer mortality were modelled using competing-risks regression. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CIs) for Cox models; sub-hazard ratios (SHR) and 95% CIs for competing-risks models.Results: a total of 187 men died during a median of 4.3 years of follow-up. Serum levels of 25(OH)D (per 1 SD decrease: HR = 1.45; 95% CI = 1.16, 1.81) and 1,25(OH)2D (per 1 SD decrease: HR = 1.20; 95% CI = 1.00, 1.44) were associated with an increased risk of all-cause mortality after adjusting for age, centre, smoking, self-reported morbidities, physical activity and functional performance. Only levels of 25(OH)D <25 nmol/l predicted cancer mortality (SHR = 3.33; 95% CI = 1.38, 8.04).Conclusion: lower 25(OH)D and 1,25(OH)2D levels independently predicted all-cause mortality in middle-aged and older European men. Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here. [ABSTRACT FROM AUTHOR]

Androgens have potent anabolic effects on skeletal muscle and decline with age in parallel to losses in muscle mass and strength. This loss of muscle mass and function, known as sarcopenia, is the central event in development of frailty, the vulnerable health status that presages adverse outcomes and rapid functional decline in older adults. The potential role of falling androgen levels in the development of frailty and their utility as function promoting therapies in older men has therefore attracted considerable attention. This review summarizes current concepts and definitions in muscle ageing, sarcopenia and frailty, and evaluates recent developments in the study of androgens and frailty. Current evidence from observational and interventional studies strongly supports an effect of androgens on muscle mass in ageing men, but effects on muscle strength and particularly physical function have been less clear. Androgen treatment has been generally well-tolerated in studies of older men, but concerns remain over higher dose treatments and use in populations with high cardiovascular risk. The first trials of selective androgen receptor modulators (SARMs) suggest similar effects on muscle mass and function to traditional androgen therapies in older adults. Important future directions include the use of these agents in combination with exercise training to promote functional ability across different populations of older adults, as well as more focus on the relationships between concurrent changes in hormone levels, body composition and physical function in observational studies. [ABSTRACT FROM AUTHOR]

Background: the link between the vitamin D endocrine axis and frailty remains undefined, with few studies examining the joint effect of vitamin D and parathyroid hormone (PTH) levels. Our objective was to determine the association of frailty with serum 25-hydroxyvitamin D (25(OH)D) and PTH.Setting: cross-sectional analysis within the European Male Ageing Study (EMAS).Participants: a total of 1,504 community-dwelling men aged 60–79 years.Methods: frailty was classified using a frailty phenotype (FP) and frailty index (FI). The association of frailty with 25(OH)D and PTH was examined using multinomial logistic regression; individual FP criteria with 25(OH)D and PTH using binary logistic regression. Results were expressed as relative odds ratios (ROR) and 95% confidence intervals (CIs) for multinomial; odds ratios (OR) and 95% CIs for binary models.Results: using the FP, 5.0% of subjects were classified as frail and 36.6% as prefrail. Lower levels of 25(OH)D were associated with being prefrail (per 1 SD decrease: ROR = 1.45; 95% CI: 1.26–1.67) and frail (ROR = 1.89; 95% CI: 1.30–2.76), after adjusting for age, centre and health and lifestyle confounders (robust group = base category). Higher levels of PTH were associated with being frail after adjustment for confounders (per 1 SD increase: ROR = 1.24; 95% CI: 1.01–1.52). Comparable results were found using the FI. Among the five FP criteria only sarcopenia was not associated with 25(OH)D levels, while only weakness was associated with PTH.Conclusion: lower 25(OH)D and higher PTH levels were positively associated with frailty in older men. Prospective data would enable the temporal nature of this relationship to be explored further. [ABSTRACT FROM PUBLISHER]

Objective: Despite the prevalence of hypogonadism (HG) and widespread use of testosterone therapy, little is known about the safety/effectiveness of long-term testosterone use. The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry assessing prostate health and other outcomes associated with testosterone treatment in men. Design: Observational patient disease registry. Methods: RHYME is a non-interventional disease registry with longitudinal data collection on a large sample ( N = 999) of well-characterized, hypogonadal men aged 18 years or older. The Registry will prospectively evaluate male patients diagnosed with HG, who have not previously been treated with testosterone therapy. Key design features include: (1) broad inclusion/exclusion criteria, (2) standardized central laboratory hormone assays, (3) independent adjudication of prostate biopsies and mortalities, (4) standard of care treatment, (5) comprehensive medical record and questionnaire data at six months and annually post-enrollment and (6) adequate statistical power for assessing prostate endpoints at 36 months. Results: A total of 25 clinical sites in six European countries (Germany, Italy, the Netherlands, Spain, Sweden and the United Kingdom) have completed recruitment for the study. Recruitment was initiated in May 2009, and completed in December 2011. Data collection is ongoing with a minimum of two years of follow-up on all patients. [ABSTRACT FROM AUTHOR]

Background: The limitations of serum testosterone and estradiol (E2) measurements using nonextraction platform immunoassays (IAs) are widely recognized. Switching to more specific mass spectrometry (MS)-based methods has been advocated, but directly comparative data on the two methods are scarce. Methods:We compared serumtestosterone and E2measurements in a large sample of middle-aged/elderly men using a common platform IA and a gas chromatography (GC)-MS method, in order to assess their limitations and advantages, and to diagnose male hypogonadism. Of subjects from the European Male Aging Study (nZ3174; age 40-79 years), peripheral serum testosterone and E2 were analyzed using established commercial platform IAs (Roche Diagnostics E170) and in-house GC-MS methods. Results: Over a broad concentration range, serum testosterone concentration measured by IA and MS showed high correlation (RZ0.93, P!0.001), which was less robust in the hypogonadal range (!11 nmol/l; RZ0.72, P!0.001). The IA/MS correlation was weaker in E2 measurements (RZ0.32, P!0.001, at E2 !40.8 pmol/l, and RZ0.74, P!0.001, at E2 O40.8 pmol/l). Using MS as the comparator method, IAascertained lowtestosterone compatible with hypogonadism(!11 nmol/l),with 75% sensitivity and 96.3% specificity. The same parameters with IA for the detection of low E2 (!40.7 pmol/l) were 13.3 and 99.3%, and for high E2 (O120 pmol/l) 88.4 and 88.6%. Conclusion: A validated platform IA is sufficient to detect subnormal testosterone concentrations in the diagnosis ofmale hypogonadism. The IAused for E2 measurements showed poor correlation with MS and may only be suitable for the detection of high E2 in men. [ABSTRACT FROM AUTHOR]

Objective: Interrelationships between hormones of the hypothalamic-pituitary-testicular (HPT) axis, hypogonadism, vitamin D and seasonality remain poorly defined. We investigated whether HPT axis hormones and hypogonadism are associated with serum levels of 25-hydroxyvitamin D (25(OH)D) in men. Design and methods: Cross-sectional survey of 3369 community-dwelling men aged 40-79 years in eight European centres. Testosterone (T), oestradiol (E2) and dihydrotestosterone were measured by gas chromatography-mass spectrometry; LH, FSH, sex hormone binding globulin (SHBG), 25(OH)D and parathyroid hormone by immunoassay. Free T was calculated from total T, SHBG and albumin. Gonadal status was categorised as eugonadal (normal T/LH), secondary (low T, low/normal LH), primary (low T, elevated LH) and compensated (normal T, elevated LH) hypogonadism. Associations of HPT axis hormones with 25(OH)D were examined using linear regression and hypogonadism with vitamin D using multinomial logistic regression. Results: In univariate analyses, free T levels were lower (P=0.02) and E2 and LH levels were higher (P<0.05) in men with vitamin D deficiency <25(OH)D !50 nmol/l). 25(OH)D was positively associated with total and free T and negatively with E2 and LH in age- and centre-adjusted linear regressions. After adjusting for health and lifestyle factors, no significant associations were observed between 25(OH)D and individual hormones of the HPT axis. However, vitamin D deficiency was significantly associated with compensated (relative risk ratio (RRR)=1.52, P=0.03) and secondary hypogonadism (RRR=1.16, P=0.05). Seasonal variation was only observed for 25(OH)D (P<0.001). Conclusions: Secondary and compensated hypogonadism were associated with vitamin D deficiency and the clinical significance of this relationship warrants further investigation. [ABSTRACT FROM AUTHOR]

Background. Testosterone increases lean mass and may help to counter the changes in muscle architecture associated with sarcopenia. This study was designed to investigate the effects of testosterone replacement therapy on skeletal muscle architecture in intermediate-frail and frail elderly men. Methods. A subgroup of 30 intermediate-frail and frail elderly men (65–89 years) with low to borderline-low testosterone levels were enrolled from a single-center randomized, double-blind placebo-controlled trial. Participants received either a transdermal testosterone (50 mg) or placebo gel daily for 6 months. Architecture (muscle thickness, fascicle length, and pennation angle) of the gastrocnemius medialis muscle was assessed by ultrasound imaging at baseline and after 6 months of treatment. Results. Serum testosterone increased from 11.6 ± 3.5 to 18.0 ± 8.1 nmol/L by 10 days after randomization in the active group (but not the placebo group) and was maintained throughout the treatment period. Testosterone treatment resulted in a preservation of muscle thickness at 6 months while it decreased in the placebo group (effect size 1.4 [95% confidence interval = 0.3–2.5; p = .015]). There was no significant effect of treatment on fascicle length (effect size 1.9 mm [95% confidence interval = −1.2 to 5.0 mm; p = .22]) or pennation angle (effect size 1.2° [95% confidence interval = −1.3 to 3.7°; p = .32]). Conclusions. Testosterone replacement in intermediate-frail and frail elderly men is associated with preservation of muscle thickness. The results suggest that testosterone mitigates sarcopenia by improving muscle tissue to maintain a state of normality in aging men. [ABSTRACT FROM PUBLISHER]

Objectives The aim of this study was to investigate the association between the catechol-O-methyltransferase (COMT) ‘pain sensitivity’ haplotypes and chronic widespread pain (CWP) in two distinct cohorts. Methods Cases of CWP and controls free of pain were selected from two population-based studies: the Epidemiology of Functional Disorders study (EPIFUND) (UK) and the European Male Ageing Study (European). The number of cases and controls were 164 and 172, and 204 and 935, respectively. Identical American College of Rheumatology criteria were used in both studies to ascertain CWP status. The EPIFUND study had three time points and cases were classified as subjects with CWP at two or three time points and controls as those free of pain at all three time points. Four single nucleotide polymorphisms (SNP): rs6269, rs4633, rs4818 and rs4680 (V158M) were genotyped using Sequenom technology. Allele and genotype frequencies were compared and haplotype analysis was conducted using PLINK software. Results No differences in allele or genotype frequencies for any of the four SNP were observed between cases and controls for either cohort. Haplotype analysis also showed no difference in the frequency of haplotypes between cases and controls. Conclusions There was no evidence of association between the ‘pain sensitivity’ haplotypes and CWP in two population-based cohorts. [ABSTRACT FROM PUBLISHER]

Background and aims Metabolic syndrome has been reported to have adverse effects on cognition although the results are conflicting. We investigated the association between metabolic syndrome and cognitive function in a population sample of middle-aged and older European men and whether any observed association could be explained by lifestyle or other confounding factors. Methods A total of 3369 men in the 40- to 79-year age group were recruited from population registers in eight centres for participation in the European Male Ageing Study. The subjects completed a questionnaire instrument and several cognitive function tests including the Rey-Osterrieth Complex Figure test, the Camden Topographical Recognition Memory test and the Digit Symbol Substitution Test. Metabolic syndrome data were assessed at an invited visit and metabolic syndrome was defined by the National Cholesterol Education Program's Adult Treatment Panel-III criteria. Associations between cognitive performance and metabolic syndrome were explored using linear regression. Results Complete cognitive and metabolic syndrome data from 3152 subjects were included in the analysis, of whom 1007 (32%) fulfilled criteria for metabolic syndrome. After adjustment for putative health and lifestyle confounders, no significant associations were found between any of the cognitive function scores and metabolic syndrome or between cognitive performance and high-sensitivity C-reactive protein. Analysis of the individual metabolic syndrome factors, however, revealed an inverse association between the level of glucose and cognitive performance. Conclusions Metabolic syndrome was not associated with cognitive impairment in this population. Of the individual components of the syndrome, diabetes was associated with poorer performances in memory, executive functions and processing speed, associations that warrant further investigation. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We examined the distribution of quantitative heel ultrasound (QUS) parameters in population samples of European men and looked at the influence of lifestyle factors on the occurrence of these parameters. Men aged between 40 and 79 years were recruited from eight European centers and invited to attend for an interviewer-assisted questionnaire, assessment of physical performance, and quantitative ultrasound (QUS) of the calcaneus (Hologic; Sahara). The relationships between QUS parameters and lifestyle variables were assessed using linear regression with adjustments for age, center, and weight. Three thousand two hundred fifty-eight men, mean age 60.0 years, were included in the analysis. A higher PASE score (upper vs. lower tertile) was associated with a higher BUA (beta coefficient = 2.44 dB/ Mhz), SOS (beta = 6.83 m/s), and QUI (beta = 3.87). Compared to those who were inactive, those who walked or cycled more than an hour per day had a higher BUA (beta = 3.71 dB/Mhz), SOS (beta = 6.97 m/s), and QUI (beta = 4.50). A longer time to walk 50 ft was linked with a lower BUA (beta = -0.62 dB/ Mhz), SOS (beta = -1.06 m/s), and QUI (beta = -0.69). Smoking was associated with a reduction in BUA, SOS, and QUI. There was a U-shaped association with frequency of alcohol consumption. Modification of lifestyle, including increasing physical activity and stopping smoking, may help optimize bone strength and reduce the risk of fracture in middle-aged and elderly European men. [ABSTRACT FROM AUTHOR]

Objectives We determined levels of cognitive functioning in community dwelling men aged 40–79 (n = 3265) from eight European centres and investigated to what extent cognitive performance varied between centres, the association between different cognitive domains and age, educational level, co-morbidity and lifestyle factors and the respective contributions of centre and individual factors to cognitive performance. Methods Cognitive domains assessed were visuo-constructional ability and visual memory (Rey–Osterrieth Complex Figure test, ROCF), topographical memory (Camden Topographical Recognition Memory test, CTRM) and processing speed (Digit-Symbol Substitution test, DSST). Results There were significant between-centre differences in all four cognitive test scores. Using multilevel linear regression analysis (MLRA), age, education, depression, physical performance and smoking were independent predictors of cognitive function and these variables explained 10–13% of the variation in cognitive scores between centres and 17–36% of the variation in scores between individuals within centres. Conclusion Our data suggest that although a proportion of the variance in cognitive function among European men is explained by individual level differences, a significant proportion is due to contextual phenomenon. Such contextual factors need to be considered when analysing multi-centre data and European men should not be treated as homogeneous when assessing cognitive performance using existing instruments. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article features the implication of late-onset hypogonadism (LOH) in males worldwide. It is a clinical and biochemical syndrome associated with advancing age, characterized by deficiency in serum testosterone levels. Data shows that there is an increasing cases of androgen deficiency in males, indicating that testosterone falls progressively with age. It was also found that the percentage of men over 60 years of age have serum testosterone levels which are below the limits of young adults.

Life expectancy is increasing in most developed countries, in part due to improved socioeconomic conditions and in part to advances in healthcare. It is widely acknowledged that the promotion of healthy ageing by delaying, minimizing or preventing disabilities or diseases is one of the most important public health objectives in this century. In contrast to the menopausal transition in females, we know relatively little about the contribution of androgens and anabolic hormones to the quality of ageing in men. The European Male Ageing Study (EMAS) is a multicentre prospective cohort designed to examine the prevalence, incidence and geographical distribution of gender-specific and general symptoms of ageing in men, including their endocrine, genetic and psychosocial predictors. Men aged 40–79 years were recruited from eight European centres: Florence (Italy), Leuven (Belgium), Lodz (Poland), Malmö (Sweden), Manchester (UK), Santiago de Compostela (Spain), Szeged (Hungary) and Tartu (Estonia). Subjects were recruited from population registers and those who agreed to take part completed a detailed questionnaire including aspects of personal and medical history, lifestyle factors and sexual function. Objective measures of body size, cognition, vision, skeletal health and neuromuscular function were obtained. Blood and DNA specimens were collected for a range of biochemical and genetic analyses. After an average of 4 years, it is planned to resurvey the participants with similar assessments. A total of 3369 men with a mean age of 60 ± 11 years were recruited. The mean centre response rate was 43%, and highest in those aged 50–59 years. Those who participated were marginally younger than those who were invited but declined to participate (60.0 vs. 61.1 years). Participants left education slightly later than a sample of non-participants, though there were no consistent differences in levels of general health, physical activity, or smoking. EMAS will provide new population-based data concerning the main features that characterize ageing in men and its critical determinants, particularly with reference to age-related changes in hormone levels. Such information is an important prerequisite to develop effective strategies to reduce age-related disabilities and optimise health and well-being into old-age. [ABSTRACT FROM AUTHOR]

Background: Administration of testosterone inhibits gonadotrophin secretion and spermatogenesis in men but the degree of response is highly variable. This treatment also stimulates prolactin, itself a progonadal hormone in animals. This study investigated whether concomitant suppression of prolactin (PRL) with the non-ergot, dopamine receptor agonist quinagolide (Q), would enhance the efficacy of testosterone in its inhibition of spermatogenesis in healthy eugonadal men.Methods: A total of 46 men were randomized to three treatment groups: Group 1, T1200: 1200 mg testosterone implant plus daily oral placebo; Group 2, T1200 + Q: 1200 mg testosterone plus oral Q 75 microg/day; Group 3, T800 + Q: testosterone 800 mg plus oral Q 75 microg/day. After an initial pre-treatment period of 4 weeks, subjects were treated for 24 weeks followed by an 8-week recovery period.Results: The total numbers of subjects that achieved severe oligospermia (< or =10(6)/ml including azoospermia) from weeks 8-16 were 11/13 (85%), 11/12 (92%), 8/13 (61.5%) in the three groups respectively.Conclusions: The results show that inhibition of PRL does not to confer additional efficacy in spermatogenic suppression in men. However, Q did not totally block PRL secretion in the subjects, possibly because testosterone replacement itself stimulated PRL by a direct action on the lactotroph, thus the effectiveness of dual inhibition of gonadotrophin and PRL could not be fully investigated. [ABSTRACT FROM AUTHOR]

OBJECTIVEThe ratio of urinary testosterone (T) to epitestosterone (EpiT) is used to detect T abuse in sport. Also, plasma or urinary concentrations of EpiT have been measured to assess testicular steroidogenesis during hormonal male contraception. Further investigations are required to evaluate the relative contributions of the testis and adrenal to EpiT production. To this purpose, we have compared basal urinary EpiT glucuronide and plasma EpiT and the response to synthetic adrenocorticotrophic hormone (ACTH) stimulation between eugonadal and hypogonadal men. DESIGN AND SUBJECTSThe basal urinary excretion rate of EpiT glucuronide was determined in 34 eugonadal men. Six men, clinically diagnosed as hypogonadal, and 6 out of the 34 eugonadal men previously described, received an intramuscular injection of synthetic ACTH depot (1 mg) at 0800 h on two consecutive days. Blood samples were collected prior to and then at 1.5, 8, 24, 25.5, 32 and 48 h with respect to the first administration (0 h). 24-h urine specimens were collected from 0800 h on days 1 and 2 (baseline) and 3 and 4 (stimulation). MEASUREMENTSPlasma EpiT, T and cortisol were measured by RIA and urinary EpiT and T, following glucuronide hydrolysis, by gas chromatography-mass spectrometry (extract combines aglycones with a minor amount of urinary free steroids). RESULTSBasal excretion rates of EpiT glucuronide in eugonadal men (range:62–751 nmol/24 h) were considerably greater than in hypogonadal men (range: 3–34 nmol/24 h). Mean basal plasma EpiT in eugonadal men (1.32 ± 0.08 nmol/l) were greater than in hypogonadal men (0.68 ± 0.04 nmol/l). In each group, synthetic ACTH stimulation increased plasma cortisol 4-fold. In eugonadal men, plasma and urinary EpiT were unchanged whereas plasma and urinary T glucuronide decreased in response to ACTH. In hypogonadal patients, ACTH increased plasma and urinary EpiT while plasma T remained unchanged. CONCLUSIONThe testes are the major... [ABSTRACT FROM AUTHOR]

Muscle wasting in older men may be related to androgen deficiency. We have assessed the effect of testosterone replacement therapy on muscle function in the upper and lower limbs of older (age >60 years) men with blood testosterone levels < 14 nmol/L. Subjects (n = 7 per group) received testosterone enanthate 200 mg i.m. or placebo every 2 weeks in a double blind study over a 12-week period and underwent muscle testing every 4 weeks. A significant increase in blood levels of testosterone and a reduction in levels of sex hormone binding globulin occurred in the treatment group. Total body mass, haemoglobin and packed cell volume also increased significantly (p < 0.05). No improvements in handgrip strength, isometric strength of knee flexors and extensors or leg extensor power were seen in either group. Wide variability in all measures of muscle function were observed in these elderly men suggesting that very large study groups would be required to determine potential treatment benefits on muscle function. [ABSTRACT FROM AUTHOR]

An empirical study investigated the association between testosterone and aggression in a sample of young male medical students: 101 volunteers completed the Aggression Questionnaire [Buss et al. (1992) Journal of Personality and Social Psychology 63:452–459] and the Conflict Tactics Scales [Straus (1979) Journal of Marriage and the Family 41:75–88] and gave a blood sample to measure testosterone levels. Neither total testosterone nor the free androgen index correlated significantly with any of the aggression subscales (physical, verbal, anger, and hostility) or with the Conflict Tactics Scales measure. This finding applied to both Caucasian and Asian respondents. Since this was one of several null results among an overall finding of a positive association, a meta-analysis of previous studies involving student samples and those from aggression-prone populations was undertaken. A weighted mean of d = .40 was obtained from 18 studies, but no differences were found between the magnitude of effect in the two types of sample. Of several other study characteristics, only the source of the testosterone assay influenced effect size magnitude, those from salivary samples being higher than those from plasma samples. Aggr. Behav. 24:411–420, 1998. © 1998 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Global ageing poses a substantial economic burden on health and social care costs. Enabling a greater proportion of older people to stay healthy for longer is key to the future sustainability of health, social and economic policy. Frailty and associated decrease in resilience plays a central role in poor health in later life. In this study, we present a population level assessment of the metabolic phenotype associated with frailty. Analysis of serum from 1191 older individuals (aged between 56 and 84 years old) and subsequent longitudinal validation (on 786 subjects) was carried out using liquid and gas chromatography-mass spectrometry metabolomics and stratified across a frailty index designed to quantitatively summarize vulnerability. Through multivariate regression and network modelling and mROC modeling we identified 12 significant metabolites (including three tocotrienols and six carnitines) that differentiate frail and non-frail phenotypes. Our study provides evidence that the dysregulation of carnitine shuttle and vitamin E pathways play a role in the risk of frailty. Risk of age-related chronic disorders and decrease in resilience is associated with ageing. Here the authors analyse the human blood metabolome and identify metabolites associated with frailty. [ABSTRACT FROM AUTHOR]