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Thang S Han, Abdelouahid Tajar, Terence W O'Neill, Min Jiang, György Bartfai, Steven Boonen, Felipe Casanueva, Joseph D Finn, Gianni Forti, Aleksander Giwercman, Ilpo T Huhtaniemi, Krzysztof Kula, Neil Pendleton, Margus Punab, Alan J Silman, Dirk Vanderschueren, Michael E J Lean, Frederick C W Wu, and the EMAS group

Background

Few published data link overweight and obesity with measures of quality of life (QoL) including sexual health in men.

Objective

To assess the association of overweight/obesity with impairment of physical and psychological QoL and sexual functions in men.

Design and setting

Cross-sectional, multicentre survey of 3369 community-dwelling men aged 40–79 (mean±s.d., 60±11) years randomly selected from eight European centres.

Outcomes

Adiposity was assessed by body mass index (BMI) and waist circumference (WC), QoL and functional impairments by physical and psychological function domains of the Short Form-36 questionnaire, Beck's Depression Inventory and the European Male Ageing Study sexual function questionnaire.

Results

Complete data on sexual activities and erectile function were available in 2734 (92%) and 3193 (95%) of the participants respectively. From the population studied, 814 men were obese (BMI ≥30 kg/m2) and 1171 had WC ≥102 cm, 25% of all men were unable to do vigorous activity and 2–13% reported depressive symptoms. Symptoms of sexual dysfunction ranged between 22% (low sexual desire) and 40% (infrequent morning erections) of the participants. Among obese men with both BMI ≥30 kg/m2 and WC ≥102 cm, at least one symptom of impaired physical, psychological and sexual function was reported by 41, 43 and 73% of the participants respectively. Compared with the reference group of non-obese men (BMI <30 kg/m2 and WC <102 cm), men with BMI ≥30 kg/m2 and WC ≥102 cm more frequently reported at least one symptom of impaired physical function (odds ratio (OR)=2.67; confidence interval (CI): 2.07–3.45, P<0.001), impaired psychological function (OR=1.48; CI: 1.14–1.90, P<0.01) and impaired sexual function (OR=1.45; CI: 1.14–1.85, P<0.01). These functional impairments were also more prevalent in men who had WC ≥102 cm even with BMI <30 kg/m2, but those with BMI ≥30 kg/m2 and WC <102 cm generally did not suffer from increased impaired physical or sexual health. Men with high BMI and WC were at even greater likelihood of having a composite of two or more or three or more symptoms compared with those with normal BMI and WC.

Conclusions

Men with high WC, including those who are ‘non-obese’ with BMI <30 kg/m2, have poor QoL with symptoms of impaired physical, psychological and sexual functions. Health promotion to improve QoL should focus on prevention of obesity and central fat accumulation.

Free access

David M Lee, Abdelouahid Tajar, Stephen R Pye, Steven Boonen, Dirk Vanderschueren, Roger Bouillon, Terence W O'Neill, Gyorgy Bartfai, Felipe F Casanueva, Joseph D Finn, Gianni Forti, Aleksander Giwercman, Thang S Han, Ilpo T Huhtaniemi, Krzysztof Kula, Michael E J Lean, Neil Pendleton, Margus Punab, Frederick C W Wu, and the EMAS study group

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.

Free access

Ilpo T Huhtaniemi, Abdelouahid Tajar, David M Lee, Terence W O'Neill, Joseph D Finn, György Bartfai, Steven Boonen, Felipe F Casanueva, Aleksander Giwercman, Thang S Han, Krzysztof Kula, Fernand Labrie, Michael E J Lean, Neil Pendleton, Margus Punab, Alan J Silman, Dirk Vanderschueren, Gianni Forti, Frederick C W Wu, and the EMAS Group

Background

The limitations of serum testosterone and estradiol (E2) measurements using non-extraction 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 serum testosterone and E2 measurements 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 (n=3174; 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 (R=0.93, P<0.001), which was less robust in the hypogonadal range (<11 nmol/l; R=0.72, P<0.001). The IA/MS correlation was weaker in E2 measurements (R=0.32, P<0.001, at E2 <40.8 pmol/l, and R=0.74, P<0.001, at E2 >40.8 pmol/l). Using MS as the comparator method, IA ascertained low testosterone 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 (>120 pmol/l) 88.4 and 88.6%.

Conclusion

A validated platform IA is sufficient to detect subnormal testosterone concentrations in the diagnosis of male hypogonadism. The IA used for E2 measurements showed poor correlation with MS and may only be suitable for the detection of high E2 in men.

Free access

David M Lee, Martin K Rutter, Terence W O'Neill, Steven Boonen, Dirk Vanderschueren, Roger Bouillon, Gyorgy Bartfai, Felipe F Casanueva, Joseph D Finn, Gianni Forti, Aleksander Giwercman, Thang S Han, Ilpo T Huhtaniemi, Krzysztof Kula, Michael E J Lean, Neil Pendleton, Margus Punab, Alan J Silman, Frederick C W Wu, and the European Male Ageing Study Group

Objectives

Low serum 25-hydroxyvitamin D (25(OH)D) and elevated parathyroid hormone (PTH) levels have been linked to insulin resistance, the metabolic syndrome (MetS) and its components. Data in healthy, community-dwelling Europeans are lacking, and previous studies have not excluded subjects receiving drug treatments that may distort the relationship between 25(OH)D/PTH and MetS. The aim of our analysis was to examine the association of 25(OH)D and PTH with Adult Treatment Panel III-defined MetS in middle-aged and older European men.

Design

This was a population-based, cross-sectional study of 3369 men aged 40–79 years enrolled in the European Male Ageing Study.

Results

After exclusion of subjects with missing data, 3069 men with a mean (±s.d.) age of 60±11 years were included in the analysis. Age-adjusted 25(OH)D levels were inversely associated with waist circumference, systolic blood pressure (BP), triglycerides, and glucose (all P<0.01). Age-adjusted PTH levels were only associated with waist and diastolic BP (both P<0.05). After adjusting for age, centre, season and lifestyle factors the odds for MetS decreased across increasing 25(OH)D quintiles (odds ratios 0.48 (95% confidence intervals 0.36–0.64) highest versus lowest quintile; Ptrend<0.001). This relationship was unchanged after adjustment for PTH, but was attenuated after additional adjustment for homoeostasis model assessment of insulin resistance (0.60 (0.47–0.78); Ptrend<0.001). There was no association between PTH and MetS.

Conclusions

Our results demonstrate an inverse relationship between 25(OH)D levels and MetS, which is independent of several confounders and PTH. The relationship is partly explained by insulin resistance. The clinical significance of these observations warrants further study.

Free access

Robert J A H Eendebak, Ilpo T Huhtaniemi, Stephen R Pye, Tomas Ahern, Terence W O’Neill, György Bartfai, Felipe F Casanueva, Mario Maggi, Gianni Forti, Robert D Alston, Aleksander Giwercman, Thang S Han, Krzysztof Kula, Michael E J Lean, Margus Punab, Neil Pendleton, Brian G Keevil, Dirk Vanderschueren, Martin K Rutter, Gindo Tampubolon, Royston Goodacre, Frederick C W Wu, and for the EMAS Group

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.